Cardioprotective Effect of Remote Ischemic Preconditioning with Postconditioning on Donor Hearts in Patients Undergoing Heart Transplantation: a single-center, double-blind, randomized controlled trial

Cardioprotective Effect of Remote Ischemic Preconditioning with Postconditioning on Donor Hearts in Patients Undergoing Heart Transplantation: a single-center, double-blind, randomized controlled trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Cardioprotective Effect of Remote Ischemic Preconditioning with Postconditioning on Donor Hearts in Patients Undergoing Heart Transplantation: a single-center, double-blind, randomized controlled trial Guyan Wang, Ying Zhang, Lijing Yang, Yimeng Chen, Zhongrong Fang, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.182/v3 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Apr, 2019 Read the published version in BMC Anesthesiology → Version 3 posted 4 You are reading this latest preprint version Show more versions Abstract Background Cardioprotective effect of remote ischemic preconditioning (RIPC) in cardiovascular surgery is controversy. This study investigated whether RIPC combined with remote ischemic postconditioning (RIPostC) reduces myocardial injury on donor hearts in patients undergoing heart transplantation. Methods One hundred and twenty patients scheduled for orthotopic heart transplantation were enrolled and randomly assigned to an RIPC+RIPostC group (n=60) or a control (n=60) group. In the RIPC+RIPostC group, four cycles of 5-min ischemia and 5-min reperfusion were applied on the right upper limb by a cuff inflated to 200mmHg after anesthesia induction (RIPC) and 20 minutes after aortic declamping (RIPostC). Serum cardiac troponin I (cTnI) level was determined preoperatively and at 3, 6, 12, 24 h after aortic declamping. Postoperative clinical outcomes were recorded. The primary endpoint was comparison of the cTnI levels at 6 h after aortic declamping. Results Compare with the preoperative baseline, serum cTnI levels peaked at 6h after aortic declamping in two groups. Compare with the control group, RIPC+RIPostC significantly reduced the serum cTnI levels at 6h after aortic declamping (38.87±31.81 vs 69.30±34.13ng/ml, P=0.018). There was no significant difference in in-hospital morbidity and mortality between the two groups. Conclusion In patients undergoing orthotopic heart transplantation, RIPC combined with RIPostC reduced myocardial injury at 6h after aortic declamping,while we found no evidence of this function provided by RIPC+RIPostC could improve clinical outcomes Internal Medicine Specialties ischemia preconditioning postconditioning heart transplantation Figures Figure 1 Figure 2 Background The myocardium is susceptible to ischemia reperfusion injury (IRI) during cardiac surgery and known to be associated with adverse outcomes [1, 2]. The number of patients requiring heart transplantation will increase, and IRI is an inevitable consequence of heart transplantation [3, 4]. Although the long-term survival and quality of life of transplant recipients have improved significantly, strategies for improving myocardial protection and perioperative mortality rates have not substantially changed [5]. Therefore, efforts continue to devise an effective myocardial protective strategy for patients undergoing heart transplantation. In early clinical studies, compared with ischemic preconditioning, remote ischemic preconditioning (RIPC) can be implemented through a simple, inexpensive and non-invasive technique, such as using a pneumatic cuff to cause transient limb ischemia [6]. In previous clinical trials, RIPC exerted a powerful protective effect on myocardial injury and significantly attenuated postoperative troponin increases in congenital cardiac, abdominal aortic, cardiac valve and coronary artery bypass graft (CABG) surgery [6-8]. In addition, RIPC and remote ischemic postconditioning (RIPostC) protocols are likely to provide additive protective effects. In this regard, a previous study showed that in patients undergoing off-pump CABG surgery, compared with the control group, RIPC combined with RIPostC reduced postoperative serum cTnI elevations, whereas RIPC alone did not markedly alter the results [9]. In a study of experimental animals, Andreka et al. [10] found that RIPostC also provided a cardioprotective effect. In clinical practice, Hong et al. [11] concluded that the protective effect exerted by combined preconditioning and postconditioning reduced serum cTnI elevations in patients receiving off-pump CABG surgery by 48.7%. Although RIPC+RIPostC is expected to exert an effective protective effect, no previous study has investigated the effect of RIPC +RIPostC on heart transplantation. We therefore hypothesized that RIPC with RIPostC would reduce myocardial injury in donor hearts and improve clinical outcomes in patients undergoing heart transplantation. Methods This was a single-center, prospective, double-blind, randomized controlled trial. This study was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn) with registration number ChiCTR-INR-16010234. The study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Medical Ethics Committee of Fuwai Hospital. Written informed consents were obtained from all participants prior to enrollment. Patients aged 18 to 70 years old who had end-stage heart disease and were scheduled for primary orthotopic heart transplantation between January 2017 and August 2018 at Fuwai Hospital, Beijing, China were screened and considered for random allocation. The exclusion criteria were preoperative mechanical circulatory support, peripheral vascular disease affecting the upper limbs, and redo heart transplantation. Moreover, patients taking antidiabetic sulphonylurea or glibenclamide were also excluded because these agents have been shown to abolish the effects of ischemic preconditioning [12]. On the day of surgery, eligible patients were randomly allocated to receive either RIPC+RIPostC or sham RIPC+RIPostC (control) before heart transplantation. Randomization was performed using opaque envelopes that concealed the group allocation. A research fellow who was not involved in medical treatment or data analysis performed the enrollment, group assignment, and intervention. Patients, cardiac surgeons, and postoperative intensive care staff were all blinded to treatment allocation. Remote ischemic conditioning was applied after anesthesia induction (RIPC) and 20 min after aortic declamping (RIPostC) and consisted of four 5-min cycles of right upper limb ischemia induced by a cuff inflated to 200 mmHg with an intervening 5 min of reperfusion during which the cuff was deflated. Patients in the control group underwent sham placement of the cuff around the right upper arm without inflation. Blood samples were collected to measure serum cardiac troponin I (cTnI) levels before surgery and at 3, 6, 12, and 24 h after removal of the aortic cross clamp. Premedication, anesthesia, perfusion, cardioplegia, and surgical techniques were standardised. Electrocardiography (ECG), pulse oximetry, nasopharyngeal and bladder temperature, arterial blood pressure, central venous pressure, and pulmonary artery pressure were continuously monitored. Anesthesia was induced with intravenous etomidate (0.2-0.3 mg/kg), cisatracurium (0.2-0.3 mg/kg) or rocuronium (0.6-1.5 mg/kg), sufentanyl (1-2 μg/kg), and midazolam (0.2-1 mg/kg) and maintained with propofol (0.05-0.08 mg/kg/min), sufentanyl (300 μg-500 μg) and muscle relaxants (10 mg/h). A low concentration of sevoflurane (0.5-1%) was used if necessary (during central line implantation). Orthotopic heart transplantation was conducted through median sternotomy. Standard non-pulsatile cardiopulmonary bypass (CPB) with a membrane oxygenator was used. During CPB, moderate systemic hypothermia (nasopharyngeal temperature 28°C) was maintained. The recipient’s heart was removed. Orthotopic heart transplantation was performed using a double-venous technique. All patients received basiliximab (20 mg) before incision for immune induction. Methylprednisolone (500 mg) was administered (250mg before incision and 250mg after aortic declamping). The primary endpoint was to compare serum cTnI levels at 6 h after aortic declamping between the two groups. Secondary endpoints were comparisons of serum cTnI levels at 3, 12, and 24 h after aortic declamping and postoperative clinical outcomes, including in-hospital death, new onset stroke, renal failure requiring dialysis, mechanical circulatory support, arrhythmia requiring treatment, re-operation for any cause, gastrointestinal bleeding, mechanical ventilation time, ICU length of stay, and postoperative hospital length of stay. The clinical outcomes were derived from the Society of Thoracic Surgeons (STS) database registry [13]. New onset stroke was defined as a new ischemic or hemorrhagic cerebrovascular accident with focal neurological deficit persisting >24 h and confirmed by brain computed tomography imaging. Re-operation for any cause included re-exploration for bleeding and surgical reintervention. Mechanical circulatory support was defined as postoperative use of an intra-aortic balloon pump (IABP) or extracorporeal membrane oxygenation (ECMO). Inotropic support was quantified by calculating the vasoactive inotropic score (VIS) from the mean dosage of inotropic drugs administered after CPB during surgery (Figure 1) [14]. Arrhythmia requiring treatment included ventricular fibrillation, ventricular tachycardia, and atrial fibrillation requiring intervention. Data were obtained from medical records and reviewed by two cardiologists who did not participate in the study. Statistical analysis of the data The sample size was calculated according to our pilot study, and the serum cTnI level was 66±23 ng/ml at 6 h after aortic decamping in the control group. We hypothesized that RIPC with RIPostC would significantly reduce serum cTnI levels by 30% and assumed a 5% dropout rate. To achieve 80% power at a two-sided significance level of 5%, a total of 120 patients was needed. All statistical analyses were performed using SPSS version 20.0 (IBM Corp, Armonk, NY). The Shapiro-Wilk test was used to assess the normality of the distribution. For normally distributed data, all data were described as the mean ± SD. Nonparametric data were described as the median and interquartile ranges, and categorical data were described as the number of patients and the relative frequency per patient. Normally distributed variables were compared between groups with an independent-sample T test. Continuous variables that were not normally distributed were analysed with a nonparametric test (Mann-Whitney U ). Categorical variables were compared between groups with the Chi-square test or Fisher’s exact test if the resulting matrixes contained cells with an expected count <5. All tests were two-sided, and a p value of P <0.05 was regarded as significant. This was an intention to treat analysis. Results During the study period, 144 patients were screened for eligibility; of these, 120 met the inclusion criteria and were randomized to either the RIPC+RIPostC group (n=60) or the control group (n=60). Twenty-four patients were excluded (5 for preoperative IABP support, 3 for redo heart transplantation and 16 because they refused to participate) (Figure 2). The baseline characteristics of the two groups were presented in Table 1. There was no difference in donor heart ischemia time or the details associated with orthotopic heart transplantation surgery between the two groups (Table 2). No unintended effects or harm related to the RIPC+RIPostC procedure were detected. Myocardial Injury Baseline preoperative serum cTnI levels were comparable between the two groups. Serum cTnI levels significantly increased in both groups after the operation procedure and peaked at 6 h after aortic declamping. RIPC+RIPostC significantly reduced peak cTnI levels (at 6 h) (38.87±31.81 vs 69.30±34.13 ng/ml, P =0.02). There was no significant difference in the serum level of cTnI at the other postoperative time points (Table 3). Clinical Outcomes There were no significant differences in in-hospital mortality, length of ICU stay, mechanical ventilation time, or other clinical outcomes between the two groups (Table 4). Discussion The present study is the first to demonstrate the effectiveness of RIPC combined with RIPostC in patients undergoing orthotopic heart transplantation. The results showed that compared to the control group, RIPC+RIPostC reduced serum cTnI levels in donor hearts at 6 h after aortic declamping, while we found no evidence that this effect of RIPC+RIPostC improved clinical outcomes after surgery. RIPC prevents IRI and has myocardial protective effect, which was demonstrated by the very first RIPC study. Besides, as RIPC is simple, inexpensive and non-invasive, numerous studies have been done since its debut. In clinical studies, RIPC predominantly reduced postoperative myocardial enzyme levels in cardiovascular surgery patients. Hausenloy et al. [15] induced RIPC by inducing lower limb ischemia in patients undergoing on-pump CABG, and they found that this procedure attenuated myocardial injury at 6, 12, 24, and 48 h after surgery. While this effect was confirmed by our preceding meta-analysis (see Yang et al. [16]), in our study, mortality, morbidity, and other clinical outcomes were not improved. Additionally, several studies [17-19], including two multicenter randomized clinical trials with a larger sample size in cardiac surgery reported by Hausenloy et al. [18] and Meybohm et al. [19], failed to demonstrate that RIPC exerts beneficial effects in this type of patient. There are several explanations for our results. This study tested the myocardial protective effect of RIPC+RIPostC in patients undergoing orthotopic heart transplantation, who may benefit highly from an effective preventive strategy. In the aforementioned studies (Hausenloy et al. and Meybohm et al.), most of the patients underwent CABG, and some patients underwent valve or ascending-aorta replacement or combined procedures. Postoperative complications are inherently less frequent in these types of surgery than in orthotopic heart transplantation. In addition, most patients who suffered from angina repeatedly have experienced the preconditioning of ischemia before CABG. Thus, the beneficial clinical effect of RIPC may be limited during CABG and valve or ascending-aorta replacement or combined procedures. Other clinical studies have shown that RIPC significantly reduced the rate of acute kidney injury (AKI), and renal replacement therapy was required in high-risk patients undergoing cardiac surgery [20]. It is highly likely that preconditioning is more effective in non-ischemic heart patients with a high risk and high complication rate than in patients without these factors. There are several mechanisms by which RIPC and RIPostC techniques have been applied in orthotopic heart transplantation in animals. In a study of heart porcine transplantation, the researchers found that hind limb preconditioning in a recipient animal exerted a significant cardioprotective effect on the subsequently transplanted and denervated donor heart [21]. Furthermore, Konstantinov et al. [22] demonstrated that performing RIPC in the recipient animal via a K+ATP channel decreased IRI in the donor heart following orthotopic heart transplantation. RIPostC is thought to recruit a mechanism that is completely different from that of RIPC during the reperfusion period, and the mechanism induced by RIPostC remains to be determined [23]. Our results collectively suggest that humoural mechanisms play a crucial role when the combination RIPC with RIPostC technique is used in orthotopic heart transplantation. Another possible confounding factor in our results was the use of propofol and sevoflurane for anesthetic maintenance. There was no significant difference in the use of sevoflurane in two groups in our study. Besides, the size of the sample, in which anesthesia maintained with sevoflurane, was very small (only 4 patients in the control group and 3 patients in the RIPC+ RIPostC group). Thus, the use of sevoflurane did not interfere with the results. The effect of RIPC and RIPostC may have been less affected by the use of propofol in our study than in other studies that used RIPC alone. Because the RIPostC protocol provides additive cardioprotective effects, it may offset a part of the negative effect of propofol. In addition, the dose of propofol was low (0.05-0.08 mg/kg/min) in the present study, and large doses of sufentanyl were administered. Overall, several promising effects were observed in this study even though propofol anesthesia was used. Recently, several basic studies [23]and clinical studies [24, 25] have reported conflicting results regarding the relationships among propofol, volatile anesthetics, and RIPC; thus, more evidence is needed to confirm that the influence of propofol and sevoflurane interferes with the protective effects of RIPC at different dosages and different operation types. The number of patients using inotropic drugs preoperatively was significantly larger in the control group [46(76.7%) vs. 23(38.3%); P <0.001]. One could argue that this could increase myocardial work, oxygen consumption, and potentially myocardial damage. All patients enrolled in this study were screened and randomly grouped . Furthermore, only low dose (3~5μg/kg/min) dopamine or dobutamine infused by microinfusion pump was administered when patients required inotropic drugs before surgery in our center. Moreover, dopamine and dobutamine exhibited short half-life and rapid metabolism. Thus, the difference of the number of patients using inotropic drugs in two groups had little impact on the serum cTnI levels in patients 6 h after aortic declamping (the primary endpoint). Our results showed that there was no significant difference in VIS (8.8±6.1vs.9.3±6.1; P= 0.60 ) between two groups after CPB. VIS is a score reflecting the amount of inotropic drugs support. If the intervention significantly affected myocardial protection, a lower inotrope requirement and a lower VIS after CPB would be expected. A possible explanation for this was the lack of appropriate samples, since VIS after CPB was not given at the primary endpoint. Furthermore, many factors affected the use of inotropic drugs during the operation, while the protective effect of RIPC combined with RIPostC could not significantly impact the VIS. This study has some limitations. First, this was a single-center study that included a relatively small sample size of patients who participated in a randomized controlled trial. Orthotopic heart transplantation surgery is a highly complex procedure with high demands for both the surgeon and the anesthesiologist. It was therefore unrealistic to conduct a multicenter trial. Second, the serum cTnI level is a sensitive and specific biomarker for detecting cardomyocytes injury that can reflect the amount of myocardial destruction. Although we found that serum cTnI levels were significantly reduced in our study, the number of patients enrolled was too small and a larger-scale trial is needed. Third, long-term clinical outcomes were not investigated. Conclusion The present study is the first to demonstrate the effects of RIPC with RIPostC in patients undergoing orthotopic heart transplantation. We found that applying RIPC with RIPostC reduced serum levels of the myocardial injury marker cTnI at 6 h after aortic decamping. Further studies performed to explore different clinical outcomes as primary endpoints and that include follow-up data are clearly warranted. Abbreviations RIPC: remote ischemic preconditioning; RIPostC: remote ischemic postconditioning; cTnI: cardiac troponin I; IRI: ischemia reperfusion injury; CABG: coronary artery bypass grafting Declarations Acknowledgements: We would like to thank Yongyuan Wang for her writing assistance. Funding This study was supported by Beijing Municipal Science & Technology Commission (No. Z161100000116051). The funding body didn’t play any roles in the design of the study and collection of data and in writing the manuscript. Availability of data and materials The datasets generated during the current study are not publicly available due the regulation of data management of Fuwai Hospital, but are available from the corresponding author on reasonable request. Authors’ contributions GYW conceived of the study, participated in the design of the study, supervise the study and revise the manuscript. YZ participated in the design of the study and revise the manuscript.LJY participated in the design of the study and drafted the manuscript. YMC helped analyse the data and draft the manuscript. HZ performed the statistical analysis, data interpretation. ZRF, CYZ, and GYL participated in the data collection. SS and JL helped with study conduct and revise the manuscript. All authors have read and approved the final manuscript. Ethics approval and consent to participate The local ethical committee approval was obtained from Fuwai HospitalApproval (NO:2016-836). Written informed consents were obtained from all participants before enrollment. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. References 1. Croal BL, Hillis GS, Gibson PH, Fazal MT, El-Shafei H, Gibson G, Jeffrey RR, Buchan KG, West D, Cuthbertson BH: Relationship between postoperative cardiac troponin I levels and outcome of cardiac surgery . Circulation 2006, 114 (14):1468-1475. 2. Krukenkamp IB, Levitsky S: Physiological and cellular mechanisms of myocardial protection . Am J Surg 1996, 172 (1):79-84. 3. Loor G, Shumway SJ, McCurry KR, Keshavamurthy S, Hussain S, Weide GD, Spratt JR, Al Salihi M, Koch CG: Process Improvement in Thoracic Donor Organ Procurement: Implementation of a Donor Assessment Checklist . Ann Thorac Surg 2016, 102 (6):1872-1877. 4. Burchill LJ: Heart transplantation in adult congenital heart disease. Heart (British Cardiac Society) 2016, 102 (23):1871-1877. 5. Castedo E, Segovia J, Escudero C, Olmedilla B, Granado F, Blas C, Guardiola JM, Millan I, Pulpon LA, Ugartea J: [Ischemia-reperfusion injury during experimental heart transplantation. Evaluation of trimetazidine's cytoprotective effect] . Rev Esp Cardiol 2005, 58 (8):941-950. 6. Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P: Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion . Circulation 1993, 87 (3):893-899. 7. Cheung MM, Kharbanda RK, Konstantinov IE, Shimizu M, Frndova H, Li J, Holtby HM, Cox PN, Smallhorn JF, Van Arsdell GS et al : Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans . J Am Coll Cardiol 2006, 47 (11):2277-2282. 8. Xie JJ, Liao XL, Chen WG, Huang DD, Chang FJ, Chen W, Luo ZL, Wang ZP, Ou JS: Remote ischaemic preconditioning reduces myocardial injury in patients undergoing heart valve surgery: randomised controlled trial . Heart (British Cardiac Society) 2012, 98 (5):384-388. 9. De Hert SG, Van der Linden PJ, Cromheecke S, Meeus R, Nelis A, Van Reeth V, ten Broecke PW, De Blier IG, Stockman BA, Rodrigus IE: Cardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration . Anesthesiology 2004, 101 (2):299-310. 10. Andreka G, Vertesaljai M, Szantho G, Font G, Piroth Z, Fontos G, Juhasz ED, Szekely L, Szelid Z, Turner MS et al : Remote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs . Heart (British Cardiac Society) 2007, 93 (6):749-752. 11. Hong DM, Jeon Y, Lee CS, Kim HJ, Lee JM, Bahk JH, Kim KB, Hwang HY: Effects of remote ischemic preconditioning with postconditioning in patients undergoing off-pump coronary artery bypass surgery--randomized controlled trial . Circ J 2012, 76 (4):884-890. 12. Mocanu MM, Maddock HL, Baxter GF, Lawrence CL, Standen NB, Yellon DM: Glimepiride, a novel sulfonylurea, does not abolish myocardial protection afforded by either ischemic preconditioning or diazoxide . Circulation 2001, 103 (25):3111-3116. 13. Shroyer AL, Coombs LP, Peterson ED, Eiken MC, DeLong ER, Chen A, Ferguson TB, Jr., Grover FL, Edwards FH: The Society of Thoracic Surgeons: 30-day operative mortality and morbidity risk models . Ann Thorac Surg 2003, 75 (6):1856-1864; discussion 1864-1855. 14. Yamazaki Y, Oba K, Matsui Y, Morimoto Y: Vasoactive-inotropic score as a predictor of morbidity and mortality in adults after cardiac surgery with cardiopulmonary bypass . Journal of anesthesia 2018, 32 (2):167-173. 15. Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E, Ashley E, Vichare S, Di Salvo C, Kolvekar S et al : Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial . Lancet 2007, 370 (9587):575-579. 16. Yang L, Wang G, Du Y, Ji B, Zheng Z: Remote ischemic preconditioning reduces cardiac troponin I release in cardiac surgery: a meta-analysis . Journal of cardiothoracic and vascular anesthesia 2014, 28 (3):682-689. 17. Meybohm P, Kohlhaas M, Stoppe C, Gruenewald M, Renner J, Bein B, Albrecht M, Cremer J, Coburn M, Schaelte G et al : RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow-Up . J Am Heart Assoc 2018, 7 (7). 18. Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J et al : Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery . N Engl J Med 2015, 373 (15):1408-1417. 19. Meybohm P, Bein B, Brosteanu O, Cremer J, Gruenewald M, Stoppe C, Coburn M, Schaelte G, Boning A, Niemann B et al : A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery . N Engl J Med 2015, 373 (15):1397-1407. 20. Zarbock A, Schmidt C, Van Aken H, Wempe C, Martens S, Zahn PK, Wolf B, Goebel U, Schwer CI, Rosenberger P et al : Effect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial . Jama 2015, 313 (21):2133-2141. 21. Skyschally A, Gent S, Amanakis G, Schulte C, Kleinbongard P, Heusch G: Across-Species Transfer of Protection by Remote Ischemic Preconditioning With Species-Specific Myocardial Signal Transduction by Reperfusion Injury Salvage Kinase and Survival Activating Factor Enhancement Pathways . Circ Res 2015, 117 (3):279-288. 22. Konstantinov IE, Li J, Cheung MM, Shimizu M, Stokoe J, Kharbanda RK, Redington AN: Remote ischemic preconditioning of the recipient reduces myocardial ischemia-reperfusion injury of the denervated donor heart via a Katp channel-dependent mechanism . Transplantation 2005, 79 (12):1691-1695. 23. Donato M, Evelson P, Gelpi RJ: Protecting the heart from ischemia/reperfusion injury: an update on remote ischemic preconditioning and postconditioning . Curr Opin Cardiol 2017, 32 (6):784-790. 24. Nederlof R, Weber NC, Juffermans NP, de Mol BA, Hollmann MW, Preckel B, Zuurbier CJ: A randomized trial of remote ischemic preconditioning and control treatment for cardioprotection in sevoflurane-anesthetized CABG patients . BMC anesthesiology 2017, 17 (1):51. 25. Lucchinetti E, Bestmann L, Feng J, Freidank H, Clanachan AS, Finegan BA, Zaugg M: Remote ischemic preconditioning applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass graft surgery: lack of synergy or evidence of antagonism in cardioprotection? Anesthesiology 2012, 116 (2):296-310. Tables Table 1. Baseline characteristics RIPC+RIPostC (n=60) Control (n=60) P value Demographics Age (years) 46.5±16.2 47.1±12.4 0.983 Male 45 (75.0%) 44 (73.3%) 0.835 BMI 21.6±3.7 21.4±3.2 0.990 Distribution of primary diseases Coronary heart diseases 10(16.7%) 9(15%) 0.803 Cardiomyopathy Dilated cardiomyopathy 29(48.3%) 32(53.3%) 0.584 Hypertrophic cardiomyopathy 5(8.3%) 7(11.7%) 0.543 Restrictive cardiomyopathy 3(5%) 3(5%) 1 ARVC 6(10%) 3(5%) 0.488 Alcoholic cardiomyopathy 1(1.7%) 1(1.7%) 1 Peripartum cardiomyopathy 0 1(1.7%) 1 Noncompaction of ventricular myocardium 2(3.3%) 1(1.7%) 1 Valvular heart disease 3(5.0%) 2(3.3%) 1 Behcet disease 1(1.7%) 0 1 Myocarditis 0 1(1.7%) 1 Risk factors and comorbidities Hypertension 7 (11.7%) 6 (10%) 0.518 Diabetes mellitus 13 (21.7%) 10 (16.7%) 0.487 Hypercholesterolemia 12 (20%) 12 (20%) 1 Previous myocardial infarction 6 (10%) 4 (6.7%) 0.509 Previous stroke 6 (10%) 6 (10%) 1 Previous atrial fibrillation 20 (33.3%) 20 (33.3%) 1 Previous cardiac surgery 6 (10%) 8 (13.3%) 0.570 Cardiac status Left-ventricular ejection fraction (%) >55% 4(6.7%) 3(5%) 1 35%-55% 8(13.3%) 12(20%) 0.327 <35% 47(78.3%) 45(75%) 0.666 Previous pacemaker 18(30%) 16(26.7%) 0.685 Preoperative medication Warfarin 8(13.3%) 12(20%) 0.327 β blocker 50(83.3%) 52(86.7%) 0.609 Lipid-lowering agent 3(5%) 8(13.3%) 0.114 ACE inhibitors or ARB 30(50%) 11(18.3%) <0.001 Aldosterone receptor blocker 46(76.7%) 57(95%) 0.803 Digitalis 16(26.7%) 49(81.7%) <0.001 Nitrates 5(8.3%) 12(20%) 0.670 Anti-diabetic drugs 6(10%) 8(13.3%) 0.570 Inotropic drugs 23(38.3%) 46(76.7%) <0.001 Data are mean ± SD or number (%). BMI, body mass index; ARVC, arrythmogenic right ventricular cardiomyopathy; ACE, angiotensin converting enzyme; ARB, angiotensin-II-receptor blocker; NYHA, New York Heart Association; RIPC, remote ischemic preconditioning; RIPostC, remote ischemic postconditioning Table 2. Intraoperative characteristics RIPC+RIPostC (n=60) Control (n=60) P value Length of surgery (h) 5.9±1.2 6.1±1.4 0.40 Donor heart ischemia time (h) 5.3±1.9 4.9±1.6 0.19 CPB time (min) 215.3±49.5 233.2±64.4 0.09 Aortic cross-clamp duration (min) 70.7±18.1 74.8±17.5 0.21 Reperfusion time (min) 130.3±34.0 139.3±43.7 0.21 Defibrillation after aortic declamping 18 (30%) 12 (20%) 0.23 Intraoperative ECMO 3 (5%) 3 (5%) 1 The use of sevoflurane 3(5%) 4(6.7%） 1 VIS after CPB 8.8±6.1 9.3±6.1 0.60 Data are mean±SD or number (%). CPB, cardiopulmonary bypass; ECMO, extracorporeal membrane oxygenation; RIPC, remote ischemic preconditioning; RIPostC, remote ischemic postconditioning; VIS: vascoactive-inotropic score. Table 3. cTnI levels RIPC + RIPostC (n=60) Control (n=60) P value T1 (before surgery) 0.05(0.26, 0.11) 0.04(0.02, 0.97) 0.34 T2 (3 hours after aortic declamping) 44.08±32.19 51.99±36.53 0.26 T3 (6 hours after aortic declamping) 38.87±31.81 69.30±34.13 0.02 T4 (12 hours after aortic declamping) 33.64±31.79 43.7±32.95 0.13 T5 (24 hours after aortic declamping) 30.17±26.34 31.40±26.21 0.74 Data are number of median(quartiles) or mean±SD. cTnI, cardiac troponin I; RIPC, remote ischemic preconditioning; RIPostC, remote ischemic postconditioning. Table 4. Postoperative characteristics and clinical outcomes Variables RIPC+RIPostC (n=60) Control (n=60) P value Length of ICU stay (d) 3.9(3, 5.8) 4(3, 6) 0.63 ICU stay >7d 10(16.7%) 8(13.3%) 0.61 ICU stay >14d 6(10%) 4(6.7%) 0.51 Mechanical ventilation time (h) 35(22, 44.5) 28.5(22, 41.8) 0.39 Mechanical ventilation time >48h 12(20%) 11(18.3%) 0.75 Mechanical ventilation time >72h 9(15%) 4(6.7%) 0.13 Postoperative hospital stay (d) 16(13, 22.5) 15(12.3, 22.8) 0.81 Postoperative hospital stay >28d 11(18.3%) 6(10%) 0.19 In-hospital death 2(3.3%) 0 0.50 New onset stroke 1(1.7%) 0 1 Renal failure requiring dialysis 2(3.3%) 1(1.7%) 1 IABP support 4(6.7%) 6(10%) 0.51 ECMO support 3(5%) 2(3.3%) 1 Atrial fibrillation 3(5%) 0 0.24 Use of a temporary pacemaker 4(6.7%) 0 0.12 Arrhythmia requiring treatment 4(6.7%) 1(1.7%) 0.36 Re-operation 3(5%) 3(5%) 1 Re-intubation 1(1.7%) 1(1.7%) 1 Tracheotomy 1(1.7%) 1(1.7%) 1 Pulmonary infection 14(23.3%) 24(40%) 0.05 Deep sternal infection 3(5%) 0 0.24 Gastrointestinal bleeding 3(5%) 0 0.24 Data are median (quartiles) or number (%). ICU, intensive care unit; IABP, intra-aortic balloon pump; ECMO, extracorporeal membrane oxygenation; RIPC, remote ischemic preconditioning; RIPostC, remote ischemic postconditioning. Cite Share Download PDF Status: Published Journal Publication published 06 Apr, 2019 Read the published version in BMC Anesthesiology → Version 3 posted Editorial decision: Accept 22 Mar, 2019 Editor assigned by journal 21 Mar, 2019 Editor invited by journal 20 Mar, 2019 Submission checks completed at journal 07 Jan, 2019 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-182","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":8487,"identity":"4cb565bb-7f9f-4615-8066-d3358ad75aae","order_by":1,"name":"Guyan Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9UlEQVRIiWNgGAWjYFAD9saGAx8qJOTkidfCc/jgwxlnLIwNG4jWIpGWbMzZVpHIcICAQvmIHMPPhW12efIOOWbSjPMkEhgbmB8+uoFHi+GNHGPpmW3JxYYHzphJF26TyGNnYDM2zsGnZUaOgTTvNubEjY09ZtIzt0kUMzbwsEkT0GL8m3dbfeLGZh4zad45EokNBwhokZcAeoF32+HE+Wxsyca8DURoMeB5VmbN++944gYeZmAgH5MwNmwm4Bf59uTNt3nOVCfOn/8QGJU1dXLy7M0PH+O15QCHAZQBE2LGoxxsSwP7AyiDgMpRMApGwSgYuQAAAlBOnxwpIy0AAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0003-3098-5472","institution":"Beijing Tongren Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Guyan","middleName":"","lastName":"Wang","suffix":""},{"id":8488,"identity":"4d8d41df-2c6b-4c19-b724-dcb222c9c90a","order_by":2,"name":"Ying Zhang","email":"","orcid":"","institution":"Southwest Medical 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Lei","email":"","orcid":"","institution":"Chinese Academy of Medical Sciences and Peking Union Medical College Fuwai Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Guiyu","middleName":"","lastName":"Lei","suffix":""},{"id":8495,"identity":"e17aaffb-2d7b-4f9c-aa95-4d4f7df467e9","order_by":9,"name":"Sheng Shi","email":"","orcid":"","institution":"Chinese Academy of Medical Sciences and Peking Union Medical College Fuwai Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sheng","middleName":"","lastName":"Shi","suffix":""},{"id":8496,"identity":"5ec7de1d-cdd5-4cdf-be1c-f10f3d9abe81","order_by":10,"name":"Jun Li","email":"","orcid":"","institution":"Chinese Academy of Medical Sciences and Peking Union Medical College Fuwai Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2019-01-07 21:31:01","currentVersionCode":3,"declarations":"","doi":"10.21203/rs.2.182/v3","doiUrl":"https://doi.org/10.21203/rs.2.182/v3","draftVersion":[],"editorialEvents":[{"content":"https://link.springer.com/article/10.1186/s12871-019-0720-z","type":"published","date":"2019-04-06T12:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":2607314,"identity":"67393709-1ece-4c63-820b-b0c7a55cd289","added_by":"b0e95e7b-bbe0-4bfd-bf12-a325b7db0c3e","created_at":"2020-09-25 20:49:31","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":18508,"visible":true,"origin":"","legend":"Formula for calculation of the vascoactive-inotropic score (VIS).","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-182/v3/figure_1.jpg"},{"id":2607313,"identity":"a6afa7b5-bad4-4286-b95c-50d0b0d91723","added_by":"b0e95e7b-bbe0-4bfd-bf12-a325b7db0c3e","created_at":"2020-09-25 20:49:30","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":45220,"visible":true,"origin":"","legend":"Flow chart.","description":"","filename":"figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-182/v3/figure_2.jpg"},{"id":13466287,"identity":"b6390f46-b2d6-41fe-81ac-b6c070fcb073","added_by":"auto","created_at":"2021-09-16 20:50:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1027603,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-182/v3/f91be7ea-6501-4519-a20e-11141eb039fa.pdf"}],"financialInterests":"","formattedTitle":"Cardioprotective Effect of Remote Ischemic Preconditioning with Postconditioning on Donor Hearts in Patients Undergoing Heart Transplantation: a single-center, double-blind, randomized controlled trial","fulltext":[{"header":"Background","content":"\u003cp\u003eThe myocardium is susceptible to ischemia reperfusion injury (IRI) during cardiac surgery and known to be associated with adverse outcomes [1, 2]. The number of patients requiring heart transplantation will increase, and IRI is an inevitable consequence of heart transplantation [3, 4]. Although the long-term survival and quality of life of transplant recipients have improved significantly, strategies for improving myocardial protection and perioperative mortality rates have not substantially changed [5]. Therefore, efforts continue to devise an effective myocardial protective strategy for patients undergoing heart transplantation.\u003c/p\u003e\n\u003cp\u003eIn early clinical studies, compared with ischemic preconditioning, remote ischemic preconditioning (RIPC) can be implemented through a simple, inexpensive and non-invasive technique, such as using a pneumatic cuff to cause transient limb ischemia [6]. In previous clinical trials, RIPC exerted a powerful protective effect on myocardial injury and significantly attenuated postoperative troponin increases in congenital cardiac, abdominal aortic, cardiac valve and coronary artery bypass graft (CABG) surgery [6-8]. In addition, RIPC and remote ischemic postconditioning (RIPostC) protocols are likely to provide additive protective effects. In this regard, a previous study showed that in patients undergoing off-pump CABG surgery, compared with the control group, RIPC combined with RIPostC reduced postoperative serum cTnI elevations, whereas RIPC alone did not markedly alter the results [9]. In a study of experimental animals, Andreka et al. [10] found that RIPostC also provided a cardioprotective effect. In clinical practice, Hong et al. [11] concluded that the protective effect exerted by combined preconditioning and postconditioning reduced serum cTnI elevations in patients receiving off-pump CABG surgery by 48.7%. Although RIPC+RIPostC is expected to exert an effective protective effect, no previous study has investigated the effect of RIPC +RIPostC on heart transplantation.\u003c/p\u003e\n\u003cp\u003eWe therefore hypothesized that RIPC with RIPostC would reduce myocardial injury in donor hearts and improve clinical outcomes in patients undergoing heart transplantation.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis was a single-center, prospective, double-blind, randomized controlled trial. This study was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn) with registration number ChiCTR-INR-16010234. The study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Medical Ethics Committee of Fuwai Hospital. Written informed consents were obtained from all participants prior to enrollment. \u003c/p\u003e\n\u003cp\u003ePatients aged 18 to 70 years old who had end-stage heart disease and were scheduled for primary orthotopic heart transplantation between January 2017 and August 2018 at Fuwai Hospital, Beijing, China were screened and considered for random allocation. The exclusion criteria were preoperative mechanical circulatory support, peripheral vascular disease affecting the upper limbs, and redo heart transplantation. Moreover, patients taking antidiabetic sulphonylurea or glibenclamide were also excluded because these agents have been shown to abolish the effects of ischemic preconditioning [12]. \u003c/p\u003e\n\u003cp\u003eOn the day of surgery, eligible patients were randomly allocated to receive either RIPC+RIPostC or sham RIPC+RIPostC (control) before heart transplantation. Randomization was performed using opaque envelopes that concealed the group allocation. A research fellow who was not involved in medical treatment or data analysis performed the enrollment, group assignment, and intervention. Patients, cardiac surgeons, and postoperative intensive care staff were all blinded to treatment allocation.\u003c/p\u003e\n\u003cp\u003eRemote ischemic conditioning was applied after anesthesia induction (RIPC) and 20 min after aortic declamping (RIPostC) and consisted of four 5-min cycles of right upper limb ischemia induced by a cuff inflated to 200 mmHg with an intervening 5 min of reperfusion during which the cuff was deflated. Patients in the control group underwent sham placement of the cuff around the right upper arm without inflation. Blood samples were collected to measure serum cardiac troponin I (cTnI) levels before surgery and at 3, 6, 12, and 24 h after removal of the aortic cross clamp.\u003c/p\u003e\n\u003cp\u003ePremedication, anesthesia, perfusion, cardioplegia, and surgical techniques were standardised. Electrocardiography (ECG), pulse oximetry, nasopharyngeal and bladder temperature, arterial blood pressure, central venous pressure, and pulmonary artery pressure were continuously monitored. Anesthesia was induced with intravenous etomidate (0.2-0.3 mg/kg), cisatracurium (0.2-0.3 mg/kg) or rocuronium (0.6-1.5 mg/kg), sufentanyl (1-2 μg/kg), and midazolam (0.2-1 mg/kg) and maintained with propofol (0.05-0.08 mg/kg/min), sufentanyl (300 μg-500 μg) and muscle relaxants (10 mg/h). A low concentration of sevoflurane (0.5-1%) was used if necessary (during central line implantation).\u003c/p\u003e\n\u003cp\u003eOrthotopic heart transplantation was conducted through median sternotomy. Standard non-pulsatile cardiopulmonary bypass (CPB) with a membrane oxygenator was used. During CPB, moderate systemic hypothermia (nasopharyngeal temperature 28°C) was maintained. The recipient’s heart was removed. Orthotopic heart transplantation was performed using a double-venous technique. All patients received basiliximab (20 mg) before incision for immune induction. Methylprednisolone (500 mg) was administered (250mg before incision and 250mg after aortic declamping).\u003c/p\u003e\n\u003cp\u003eThe primary endpoint was to compare serum cTnI levels at 6 h after aortic declamping between the two groups. Secondary endpoints were comparisons of serum cTnI levels at 3, 12, and 24 h after aortic declamping and postoperative clinical outcomes, including in-hospital death, new onset stroke, renal failure requiring dialysis, mechanical circulatory support, arrhythmia requiring treatment, re-operation for any cause, gastrointestinal bleeding, mechanical ventilation time, ICU length of stay, and postoperative hospital length of stay.\u003c/p\u003e\n\u003cp\u003eThe clinical outcomes were derived from the Society of Thoracic Surgeons (STS) database registry [13]. New onset stroke was defined as a new ischemic or hemorrhagic cerebrovascular accident with focal neurological deficit persisting \u0026gt;24 h and confirmed by brain computed tomography imaging. Re-operation for any cause included re-exploration for bleeding and surgical reintervention. Mechanical circulatory support was defined as postoperative use of an intra-aortic balloon pump (IABP) or extracorporeal membrane oxygenation (ECMO). Inotropic support was quantified by calculating the vasoactive inotropic score (VIS) from the mean dosage of inotropic drugs administered after CPB during surgery (Figure 1) [14]. Arrhythmia requiring treatment included ventricular fibrillation, ventricular tachycardia, and atrial fibrillation requiring intervention. Data were obtained from medical records and reviewed by two cardiologists who did not participate in the study.\u003c/p\u003e\n\u003cp\u003e\u003cb\u003eStatistical analysis of the data\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe sample size was calculated according to our pilot study, and the serum cTnI level was 66±23 ng/ml at 6 h after aortic decamping in the control group. We hypothesized that RIPC with RIPostC would significantly reduce serum cTnI levels by 30% and assumed a 5% dropout rate. To achieve 80% power at a two-sided significance level of 5%, a total of 120 patients was needed.\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using SPSS version 20.0 (IBM Corp, Armonk, NY). The Shapiro-Wilk test was used to assess the normality of the distribution. For normally distributed data, all data were described as the mean ± SD. Nonparametric data were described as the median and interquartile ranges, and categorical data were described as the number of patients and the relative frequency per patient. Normally distributed variables were compared between groups with an independent-sample T test. Continuous variables that were not normally distributed were analysed with a nonparametric test (Mann-Whitney \u003ci\u003eU\u003c/i\u003e). Categorical variables were compared between groups with the Chi-square test or Fisher’s exact test if the resulting matrixes contained cells with an expected count \u0026lt;5. All tests were two-sided, and a \u003ci\u003ep\u003c/i\u003e value of \u003ci\u003eP\u003c/i\u003e\u0026lt;0.05 was regarded as significant. This was an intention to treat analysis.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the study period, 144 patients were screened for eligibility; of these, 120 met the inclusion criteria and were randomized to either the RIPC+RIPostC group (n=60) or the control group (n=60). Twenty-four patients were excluded (5 for preoperative IABP support, 3 for redo heart transplantation and 16 because they refused to participate) (Figure 2). \u003c/p\u003e\n\u003cp\u003eThe baseline characteristics of the two groups were presented in Table 1. There was no difference in donor heart ischemia time or the details associated with orthotopic heart transplantation surgery between the two groups (Table 2). No unintended effects or harm related to the RIPC+RIPostC procedure were detected.\u003c/p\u003e\n\u003cp\u003e\u003ci\u003eMyocardial Injury\u003c/i\u003e\u003c/p\u003e\n\u003cp\u003eBaseline preoperative serum cTnI levels were comparable between the two groups. Serum cTnI levels significantly increased in both groups after the operation procedure and peaked at 6 h after aortic declamping. RIPC+RIPostC significantly reduced peak cTnI levels (at 6 h) (38.87±31.81 vs 69.30±34.13 ng/ml, \u003ci\u003eP\u003c/i\u003e=0.02). There was no significant difference in the serum level of cTnI at the other postoperative time points (Table 3).\u003c/p\u003e\n\u003cp\u003e\u003ci\u003eClinical Outcomes\u003c/i\u003e\u003c/p\u003e\n\u003cp\u003eThere were no significant differences in in-hospital mortality, length of ICU stay, mechanical ventilation time, or other clinical outcomes between the two groups (Table 4).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe present study is the first to demonstrate the effectiveness of RIPC combined with RIPostC in patients undergoing orthotopic heart transplantation. The results showed that compared to the control group, RIPC+RIPostC reduced serum cTnI levels in donor hearts at 6 h after aortic declamping, while we found no evidence that this effect of RIPC+RIPostC improved clinical outcomes after surgery.\u003c/p\u003e\n\u003cp\u003eRIPC prevents IRI and has myocardial protective effect, which was demonstrated by the very first RIPC study. Besides, as RIPC is simple, inexpensive and non-invasive, numerous studies have been done since its debut. In clinical studies, RIPC predominantly reduced postoperative myocardial enzyme levels in cardiovascular surgery patients. Hausenloy et al. [15] induced RIPC by inducing lower limb ischemia in patients undergoing on-pump CABG, and they found that this procedure attenuated myocardial injury at 6, 12, 24, and 48 h after surgery. While this effect was confirmed by our preceding meta-analysis (see Yang et al. [16]), in our study, mortality, morbidity, and other clinical outcomes were not improved. Additionally, several studies [17-19], including two multicenter randomized clinical trials with a larger sample size in cardiac surgery reported by Hausenloy et al. [18] and Meybohm et al. [19], failed to demonstrate that RIPC exerts beneficial effects in this type of patient.\u003c/p\u003e\n\u003cp\u003eThere are several explanations for our results. This study tested the myocardial protective effect of RIPC+RIPostC in patients undergoing orthotopic heart transplantation, who may benefit highly from an effective preventive strategy. In the aforementioned studies (Hausenloy et al. and Meybohm et al.), most of the patients underwent CABG, and some patients underwent valve or ascending-aorta replacement or combined procedures. Postoperative complications are inherently less frequent in these types of surgery than in orthotopic heart transplantation. In addition, most patients who suffered from angina repeatedly have experienced the preconditioning of ischemia before CABG. Thus, the beneficial clinical effect of RIPC may be limited during CABG and valve or ascending-aorta replacement or combined procedures. Other clinical studies have shown that RIPC significantly reduced the rate of acute kidney injury (AKI), and renal replacement therapy was required in high-risk patients undergoing cardiac surgery [20]. It is highly likely that preconditioning is more effective in non-ischemic heart patients with a high risk and high complication rate than in patients without these factors. \u003c/p\u003e\n\u003cp\u003eThere are several mechanisms by which RIPC and RIPostC techniques have been applied in orthotopic heart transplantation in animals. In a study of heart porcine transplantation, the researchers found that hind limb preconditioning in a recipient animal exerted a significant cardioprotective effect on the subsequently transplanted and denervated donor heart [21]. Furthermore, Konstantinov et al. [22] demonstrated that performing RIPC in the recipient animal via a K+ATP channel decreased IRI in the donor heart following orthotopic heart transplantation. RIPostC is thought to recruit a mechanism that is completely different from that of RIPC during the reperfusion period, and the mechanism induced by RIPostC remains to be determined [23]. Our results collectively suggest that humoural mechanisms play a crucial role when the combination RIPC with RIPostC technique is used in orthotopic heart transplantation.\u003c/p\u003e\n\u003cp\u003eAnother possible confounding factor in our results was the use of propofol and sevoflurane for anesthetic maintenance. There was no significant difference in the use of sevoflurane in two groups in our study. Besides, the size of the sample, in which anesthesia maintained with sevoflurane, was very small (only 4 patients in the control group and 3 patients in the RIPC+ RIPostC group). Thus, the use of sevoflurane did not interfere with the results. The effect of RIPC and RIPostC may have been less affected by the use of propofol in our study than in other studies that used RIPC alone. Because the RIPostC protocol provides additive cardioprotective effects, it may offset a part of the negative effect of propofol. In addition, the dose of propofol was low (0.05-0.08 mg/kg/min) in the present study, and large doses of sufentanyl were administered. Overall, several promising effects were observed in this study even though propofol anesthesia was used. Recently, several basic studies [23]and clinical studies [24, 25] have reported conflicting results regarding the relationships among propofol, volatile anesthetics, and RIPC; thus, more evidence is needed to confirm that the influence of propofol and sevoflurane interferes with the protective effects of RIPC at different dosages and different operation types.\u003c/p\u003e\n\u003cp\u003eThe number of patients using inotropic drugs preoperatively was significantly larger in the control group [46(76.7%) vs. 23(38.3%); \u003ci\u003eP\u003c/i\u003e\u0026lt;0.001]. One could argue that this could increase myocardial work, oxygen consumption, and potentially myocardial damage. All patients enrolled in this study were screened and randomly grouped\u003ci\u003e.\u003c/i\u003e Furthermore, only low dose (3~5μg/kg/min) dopamine or dobutamine infused by microinfusion pump was administered when patients required inotropic drugs before surgery in our center. Moreover, dopamine and dobutamine exhibited short half-life and rapid metabolism. Thus, the difference of the number of patients using inotropic drugs in two groups had little impact on the serum cTnI levels in patients 6 h after aortic declamping (the primary endpoint). \u003c/p\u003e\n\u003cp\u003eOur results showed that there was no significant difference in VIS (8.8±6.1vs.9.3±6.1; \u003ci\u003eP=\u003c/i\u003e0.60\u003ci\u003e)\u003c/i\u003e between two groups after CPB. VIS is a score reflecting the amount of inotropic drugs support. If the intervention significantly affected myocardial protection, a lower inotrope requirement and a lower VIS after CPB would be expected. A possible explanation for this was the lack of appropriate samples, since VIS after CPB was not given at the primary endpoint. Furthermore, many factors affected the use of inotropic drugs during the operation, while the protective effect of RIPC combined with RIPostC could not significantly impact the VIS. \u003c/p\u003e\n\u003cp\u003eThis study has some limitations. First, this was a single-center study that included a relatively small sample size of patients who participated in a randomized controlled trial. Orthotopic heart transplantation surgery is a highly complex procedure with high demands for both the surgeon and the anesthesiologist. It was therefore unrealistic to conduct a multicenter trial. Second, the serum cTnI level is a sensitive and specific biomarker for detecting cardomyocytes injury that can reflect the amount of myocardial destruction. Although we found that serum cTnI levels were significantly reduced in our study, the number of patients enrolled was too small and a larger-scale trial is needed. Third, long-term clinical outcomes were not investigated.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe present study is the first to demonstrate the effects of RIPC with RIPostC in patients undergoing orthotopic heart transplantation. We found that applying RIPC with RIPostC reduced serum levels of the myocardial injury marker cTnI at 6 h after aortic decamping. Further studies performed to explore different clinical outcomes as primary endpoints and that include follow-up data are clearly warranted.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eRIPC: remote ischemic preconditioning; RIPostC: remote ischemic postconditioning; cTnI: cardiac troponin I; IRI: ischemia reperfusion injury; CABG: coronary artery bypass grafting\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cb\u003eAcknowledgements:\u003c/b\u003e\u003c/p\u003e\n\u003cp class=\"normal_(Web)\"\u003eWe would like to thank Yongyuan Wang for her writing assistance. \u003c/p\u003e\n\u003cp\u003e\u003cb\u003eFunding\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by Beijing Municipal Science \u0026amp; Technology Commission (No. Z161100000116051). The funding body didn’t play any roles in the design of the study and collection of data and in writing the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cb\u003eAvailability of data and materials \u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during the current study are not publicly available due the regulation of data management of Fuwai Hospital, but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cb\u003eAuthors’ contributions\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eGYW conceived of the study, participated in the design of the study, supervise the study and revise the manuscript. YZ participated in the design of the study and revise the manuscript.LJY participated in the design of the study and drafted the manuscript. YMC helped analyse the data and draft the manuscript. HZ performed the statistical analysis, data interpretation. ZRF, CYZ, and GYL participated in the data collection. SS and JL helped with study conduct and revise the manuscript. All authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp class=\"normal_(Web)\"\u003e\u003cb\u003eEthics approval and consent to participate \u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe local ethical committee approval was obtained from Fuwai HospitalApproval (NO:2016-836). Written informed consents were obtained from all participants before enrollment.\u003c/p\u003e\n\u003cp\u003e\u003cb\u003eConsent for publication\u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp class=\"normal_(Web)\"\u003e\u003cb\u003eCompeting interests \u003c/b\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003cp class=\"endNote_Bibliography\"\u003e1. Croal BL, Hillis GS, Gibson PH, Fazal MT, El-Shafei H, Gibson G, Jeffrey RR, Buchan KG, West D, Cuthbertson BH: \u003cb\u003eRelationship between postoperative cardiac troponin I levels and outcome of cardiac surgery\u003c/b\u003e. \u003ci\u003eCirculation \u003c/i\u003e2006, \u003cb\u003e114\u003c/b\u003e(14):1468-1475.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e2. Krukenkamp IB, Levitsky S: \u003cb\u003ePhysiological and cellular mechanisms of myocardial protection\u003c/b\u003e. \u003ci\u003eAm J Surg \u003c/i\u003e1996, \u003cb\u003e172\u003c/b\u003e(1):79-84.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e3. Loor G, Shumway SJ, McCurry KR, Keshavamurthy S, Hussain S, Weide GD, Spratt JR, Al Salihi M, Koch CG: \u003cb\u003eProcess Improvement in Thoracic Donor Organ Procurement: Implementation of a Donor Assessment Checklist\u003c/b\u003e. \u003ci\u003eAnn Thorac Surg \u003c/i\u003e2016, \u003cb\u003e102\u003c/b\u003e(6):1872-1877.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e4. Burchill LJ: \u003cb\u003eHeart transplantation in adult congenital heart disease. \u003c/b\u003e\u003ci\u003eHeart (British Cardiac Society) \u003c/i\u003e2016, \u003cb\u003e102\u003c/b\u003e(23):1871-1877.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e5. Castedo E, Segovia J, Escudero C, Olmedilla B, Granado F, Blas C, Guardiola JM, Millan I, Pulpon LA, Ugartea J: \u003cb\u003e[Ischemia-reperfusion injury during experimental heart transplantation. Evaluation of trimetazidine's cytoprotective effect]\u003c/b\u003e. \u003ci\u003eRev Esp Cardiol \u003c/i\u003e2005, \u003cb\u003e58\u003c/b\u003e(8):941-950.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e6. Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P: \u003cb\u003eRegional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion\u003c/b\u003e. \u003ci\u003eCirculation \u003c/i\u003e1993, \u003cb\u003e87\u003c/b\u003e(3):893-899.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e7. Cheung MM, Kharbanda RK, Konstantinov IE, Shimizu M, Frndova H, Li J, Holtby HM, Cox PN, Smallhorn JF, Van Arsdell GS\u003ci\u003e et al\u003c/i\u003e: \u003cb\u003eRandomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans\u003c/b\u003e. \u003ci\u003eJ Am Coll Cardiol \u003c/i\u003e2006, \u003cb\u003e47\u003c/b\u003e(11):2277-2282.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e8. Xie JJ, Liao XL, Chen WG, Huang DD, Chang FJ, Chen W, Luo ZL, Wang ZP, Ou JS: \u003cb\u003eRemote ischaemic preconditioning reduces myocardial injury in patients undergoing heart valve surgery: randomised controlled trial\u003c/b\u003e. \u003ci\u003eHeart (British Cardiac Society) \u003c/i\u003e2012, \u003cb\u003e98\u003c/b\u003e(5):384-388.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e9. De Hert SG, Van der Linden PJ, Cromheecke S, Meeus R, Nelis A, Van Reeth V, ten Broecke PW, De Blier IG, Stockman BA, Rodrigus IE: \u003cb\u003eCardioprotective properties of sevoflurane in patients undergoing coronary surgery with cardiopulmonary bypass are related to the modalities of its administration\u003c/b\u003e. \u003ci\u003eAnesthesiology \u003c/i\u003e2004, \u003cb\u003e101\u003c/b\u003e(2):299-310.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e10. Andreka G, Vertesaljai M, Szantho G, Font G, Piroth Z, Fontos G, Juhasz ED, Szekely L, Szelid Z, Turner MS\u003ci\u003e et al\u003c/i\u003e: \u003cb\u003eRemote ischaemic postconditioning protects the heart during acute myocardial infarction in pigs\u003c/b\u003e. \u003ci\u003eHeart (British Cardiac Society) \u003c/i\u003e2007, \u003cb\u003e93\u003c/b\u003e(6):749-752.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e11. Hong DM, Jeon Y, Lee CS, Kim HJ, Lee JM, Bahk JH, Kim KB, Hwang HY: \u003cb\u003eEffects of remote ischemic preconditioning with postconditioning in patients undergoing off-pump coronary artery bypass surgery--randomized controlled trial\u003c/b\u003e. \u003ci\u003eCirc J \u003c/i\u003e2012, \u003cb\u003e76\u003c/b\u003e(4):884-890.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e12. Mocanu MM, Maddock HL, Baxter GF, Lawrence CL, Standen NB, Yellon DM: \u003cb\u003eGlimepiride, a novel sulfonylurea, does not abolish myocardial protection afforded by either ischemic preconditioning or diazoxide\u003c/b\u003e. \u003ci\u003eCirculation \u003c/i\u003e2001, \u003cb\u003e103\u003c/b\u003e(25):3111-3116.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e13. Shroyer AL, Coombs LP, Peterson ED, Eiken MC, DeLong ER, Chen A, Ferguson TB, Jr., Grover FL, Edwards FH: \u003cb\u003eThe Society of Thoracic Surgeons: 30-day operative mortality and morbidity risk models\u003c/b\u003e. \u003ci\u003eAnn Thorac Surg \u003c/i\u003e2003, \u003cb\u003e75\u003c/b\u003e(6):1856-1864; discussion 1864-1855.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e14. Yamazaki Y, Oba K, Matsui Y, Morimoto Y: \u003cb\u003eVasoactive-inotropic score as a predictor of morbidity and mortality in adults after cardiac surgery with cardiopulmonary bypass\u003c/b\u003e. \u003ci\u003eJournal of anesthesia \u003c/i\u003e2018, \u003cb\u003e32\u003c/b\u003e(2):167-173.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e15. Hausenloy DJ, Mwamure PK, Venugopal V, Harris J, Barnard M, Grundy E, Ashley E, Vichare S, Di Salvo C, Kolvekar S\u003ci\u003e et al\u003c/i\u003e: \u003cb\u003eEffect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial\u003c/b\u003e. \u003ci\u003eLancet \u003c/i\u003e2007, \u003cb\u003e370\u003c/b\u003e(9587):575-579.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e16. Yang L, Wang G, Du Y, Ji B, Zheng Z: \u003cb\u003eRemote ischemic preconditioning reduces cardiac troponin I release in cardiac surgery: a meta-analysis\u003c/b\u003e. \u003ci\u003eJournal of cardiothoracic and vascular anesthesia \u003c/i\u003e2014, \u003cb\u003e28\u003c/b\u003e(3):682-689.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e17. Meybohm P, Kohlhaas M, Stoppe C, Gruenewald M, Renner J, Bein B, Albrecht M, Cremer J, Coburn M, Schaelte G\u003ci\u003e et al\u003c/i\u003e: \u003cb\u003eRIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow-Up\u003c/b\u003e. \u003ci\u003eJ Am Heart Assoc \u003c/i\u003e2018, \u003cb\u003e7\u003c/b\u003e(7).\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e18. Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J\u003ci\u003e et al\u003c/i\u003e: \u003cb\u003eRemote Ischemic Preconditioning and Outcomes of Cardiac Surgery\u003c/b\u003e. \u003ci\u003eN Engl J Med \u003c/i\u003e2015, \u003cb\u003e373\u003c/b\u003e(15):1408-1417.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e19. Meybohm P, Bein B, Brosteanu O, Cremer J, Gruenewald M, Stoppe C, Coburn M, Schaelte G, Boning A, Niemann B\u003ci\u003e et al\u003c/i\u003e: \u003cb\u003eA Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery\u003c/b\u003e. \u003ci\u003eN Engl J Med \u003c/i\u003e2015, \u003cb\u003e373\u003c/b\u003e(15):1397-1407.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e20. Zarbock A, Schmidt C, Van Aken H, Wempe C, Martens S, Zahn PK, Wolf B, Goebel U, Schwer CI, Rosenberger P\u003ci\u003e et al\u003c/i\u003e: \u003cb\u003eEffect of remote ischemic preconditioning on kidney injury among high-risk patients undergoing cardiac surgery: a randomized clinical trial\u003c/b\u003e. \u003ci\u003eJama \u003c/i\u003e2015, \u003cb\u003e313\u003c/b\u003e(21):2133-2141.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e21. Skyschally A, Gent S, Amanakis G, Schulte C, Kleinbongard P, Heusch G: \u003cb\u003eAcross-Species Transfer of Protection by Remote Ischemic Preconditioning With Species-Specific Myocardial Signal Transduction by Reperfusion Injury Salvage Kinase and Survival Activating Factor Enhancement Pathways\u003c/b\u003e. \u003ci\u003eCirc Res \u003c/i\u003e2015, \u003cb\u003e117\u003c/b\u003e(3):279-288.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e22. Konstantinov IE, Li J, Cheung MM, Shimizu M, Stokoe J, Kharbanda RK, Redington AN: \u003cb\u003eRemote ischemic preconditioning of the recipient reduces myocardial ischemia-reperfusion injury of the denervated donor heart via a Katp channel-dependent mechanism\u003c/b\u003e. \u003ci\u003eTransplantation \u003c/i\u003e2005, \u003cb\u003e79\u003c/b\u003e(12):1691-1695.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e23. Donato M, Evelson P, Gelpi RJ: \u003cb\u003eProtecting the heart from ischemia/reperfusion injury: an update on remote ischemic preconditioning and postconditioning\u003c/b\u003e. \u003ci\u003eCurr Opin Cardiol \u003c/i\u003e2017, \u003cb\u003e32\u003c/b\u003e(6):784-790.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e24. Nederlof R, Weber NC, Juffermans NP, de Mol BA, Hollmann MW, Preckel B, Zuurbier CJ: \u003cb\u003eA randomized trial of remote ischemic preconditioning and control treatment for cardioprotection in sevoflurane-anesthetized CABG patients\u003c/b\u003e. \u003ci\u003eBMC anesthesiology \u003c/i\u003e2017, \u003cb\u003e17\u003c/b\u003e(1):51.\u003c/p\u003e\n\u003cp class=\"endNote_Bibliography\"\u003e25. Lucchinetti E, Bestmann L, Feng J, Freidank H, Clanachan AS, Finegan BA, Zaugg M: \u003cb\u003eRemote ischemic preconditioning applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass graft surgery: lack of synergy or evidence of antagonism in cardioprotection?\u003c/b\u003e \u003ci\u003eAnesthesiology \u003c/i\u003e2012, \u003cb\u003e116\u003c/b\u003e(2):296-310.\u003c/p\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003ca name=\"_GoBack\"/\u003e\u003cb\u003eTable 1.\u003c/b\u003e Baseline characteristics\u003c/p\u003e\n\u003ctable class=table\u003e\u003ctbody\u003e\u003ctr\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eRIPC+RIPostC (n=60)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eControl (n=60) \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e\u003ci\u003eP\u003c/i\u003e value\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e\u003cb\u003eDemographics\u003c/b\u003e\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Age (years)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e46.5±16.2\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e47.1±12.4 \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.983\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Male \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e45 (75.0%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e44 (73.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.835\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e BMI \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e21.6±3.7\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e21.4±3.2\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.990\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e\u003cb\u003eDistribution of primary diseases\u003c/b\u003e\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Coronary heart diseases\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e10(16.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e9(15%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.803\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Cardiomyopathy\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Dilated cardiomyopathy\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e29(48.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e32(53.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.584\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Hypertrophic cardiomyopathy\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e5(8.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e7(11.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.543\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Restrictive cardiomyopathy\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3(5%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3(5%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e ARVC\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e6(10%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3(5%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.488\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Alcoholic cardiomyopathy\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1(1.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1(1.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Peripartum cardiomyopathy\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0 \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1(1.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Noncompaction of ventricular myocardium\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2(3.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1(1.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Valvular heart disease\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3(5.0%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2(3.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Behcet disease\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1(1.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Myocarditis \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1(1.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e\u003cb\u003eRisk factors and comorbidities\u003c/b\u003e\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Hypertension\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e7 (11.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e6 (10%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.518\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Diabetes mellitus\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e13 (21.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e10 (16.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.487\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Hypercholesterolemia\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e12 (20%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e12 (20%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Previous myocardial infarction\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e6 (10%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e4 (6.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.509\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Previous stroke\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e6 (10%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e6 (10%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Previous atrial fibrillation\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e20 (33.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e20 (33.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Previous cardiac surgery\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e6 (10%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e8 (13.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.570\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e\u003cb\u003eCardiac status\u003c/b\u003e\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eLeft-ventricular ejection fraction (%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e \u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e \u0026gt;55%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e4(6.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3(5%) \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e 35%-55%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e8(13.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e12(20%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.327\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e \u0026lt;35%\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e47(78.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e45(75%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.666\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Previous pacemaker\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e18(30%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e16(26.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.685\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e\u003cb\u003ePreoperative medication\u003c/b\u003e\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Warfarin\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e8(13.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e12(20%) \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.327\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e β blocker\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e50(83.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e52(86.7%) \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.609\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Lipid-lowering agent\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3(5%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e8(13.3%) \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.114\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e ACE inhibitors or ARB\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e30(50%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e11(18.3%) \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Aldosterone receptor blocker\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e46(76.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e57(95%) \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.803\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Digitalis\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e16(26.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e49(81.7%) \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Nitrates\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e5(8.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e12(20%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.670\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Anti-diabetic drugs\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e6(10%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e8(13.3%) \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.570\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e Inotropic drugs\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e23(38.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e46(76.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003c/tbody\u003e\u003c/table\u003e\n\u003cp\u003eData are mean ± SD or number (%). \u003c/p\u003e\n\u003cp\u003eBMI, body mass index; ARVC, arrythmogenic right ventricular cardiomyopathy; ACE, angiotensin converting enzyme; ARB, angiotensin-II-receptor blocker; NYHA, New York Heart Association; RIPC, remote ischemic preconditioning; RIPostC, remote ischemic postconditioning\u003c/p\u003e\n\u003cp\u003e\u003cb\u003eTable 2. \u003c/b\u003eIntraoperative characteristics\u003c/p\u003e\n\u003ctable class=table\u003e\u003ctbody\u003e\u003ctr\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eRIPC+RIPostC (n=60)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eControl (n=60)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e\u003ci\u003eP \u003c/i\u003evalue\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eLength of surgery (h) \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e5.9±1.2\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e6.1±1.4\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.40\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eDonor heart ischemia time (h)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e5.3±1.9\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e4.9±1.6\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.19\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eCPB time (min)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e 215.3±49.5\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e 233.2±64.4\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.09\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eAortic cross-clamp duration (min)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e70.7±18.1\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e74.8±17.5\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.21\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eReperfusion time (min)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e 130.3±34.0\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e 139.3±43.7\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.21\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eDefibrillation after aortic declamping\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e 18 (30%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e12 (20%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.23\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eIntraoperative ECMO \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e 3 (5%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e 3 (5%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eThe use of sevoflurane\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e 3(5%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e4(6.7%）\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e\u003ca name=\"_GoBack\"/\u003eVIS after CPB\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e8.8±6.1\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e9.3±6.1\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.60\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003c/tbody\u003e\u003c/table\u003e\n\u003cp\u003eData are mean±SD or number (%). \u003c/p\u003e\n\u003cp\u003eCPB, cardiopulmonary bypass; ECMO, extracorporeal membrane oxygenation; RIPC, remote ischemic preconditioning; RIPostC, remote ischemic postconditioning; \u003c/p\u003e\n\u003cp\u003eVIS: vascoactive-inotropic score.\u003c/p\u003e\n\u003cbody\u003e\u003cp\u003e\u003ca name=\"_GoBack\"/\u003e\u003cb\u003eTable 3. \u003c/b\u003ecTnI levels \u003c/p\u003e\n\u003ctable class=table\u003e\u003ctbody\u003e\u003ctr\u003e\t\u003ctd\u003e\u003cp/\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eRIPC + RIPostC (n=60)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eControl (n=60)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e\u003ci\u003eP\u003c/i\u003e value\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eT1 (before surgery) \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.05(0.26, 0.11)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.04(0.02, 0.97)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.34\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eT2 (3 hours after aortic declamping) \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e44.08±32.19\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e51.99±36.53\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.26\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eT3 (6 hours after aortic declamping)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e38.87±31.81\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e69.30±34.13\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.02\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eT4 (12 hours after aortic declamping)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e33.64±31.79\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e43.7±32.95\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.13\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eT5 (24 hours after aortic declamping)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e30.17±26.34\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e31.40±26.21\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.74\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003c/tbody\u003e\u003c/table\u003e\n\u003cp\u003eData are number of median(quartiles) or mean±SD. cTnI, cardiac troponin I; RIPC, remote ischemic preconditioning; RIPostC, remote ischemic postconditioning.\u003c/p\u003e\n\u003cbody\u003e\u003cp\u003e\u003ca name=\"_GoBack\"/\u003e\u003cb\u003eTable 4. \u003c/b\u003ePostoperative characteristics and clinical outcomes\u003c/p\u003e\n\u003ctable class=table\u003e\u003ctbody\u003e\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eVariables\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eRIPC+RIPostC (n=60) \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003eControl (n=60)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e\u003ci\u003eP\u003c/i\u003e value\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eLength of ICU stay (d)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3.9(3, 5.8)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e4(3, 6)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.63\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e ICU stay \u0026gt;7d\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e10(16.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e8(13.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.61\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003e ICU stay \u0026gt;14d\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e6(10%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e4(6.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.51\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eMechanical ventilation time (h)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e35(22, 44.5)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e28.5(22, 41.8)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.39\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eMechanical ventilation time \u0026gt;48h\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e12(20%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e11(18.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.75\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eMechanical ventilation time \u0026gt;72h\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e9(15%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e4(6.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.13\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003ePostoperative hospital stay (d)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e16(13, 22.5)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e15(12.3, 22.8)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.81\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003ePostoperative hospital stay \u0026gt;28d\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e11(18.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e6(10%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.19\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eIn-hospital death\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2(3.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0 \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.50\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eNew onset stroke\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1(1.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0 \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1 \u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eRenal failure requiring dialysis\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2(3.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1(1.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eIABP support\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e4(6.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e6(10%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.51\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eECMO support\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3(5%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e2(3.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eAtrial fibrillation\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3(5%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0 \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.24 \u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eUse of a temporary pacemaker\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e4(6.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0 \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.12\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eArrhythmia requiring treatment\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e4(6.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1(1.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.36\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eRe-operation\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3(5%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3(5%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eRe-intubation\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1(1.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1(1.7%) \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eTracheotomy\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1(1.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1(1.7%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003ePulmonary infection\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e14(23.3%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e24(40%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.05\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eDeep sternal infection\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3(5%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e 0 \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.24\u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003ctr\u003e\t\u003ctd\u003e\u003cp\u003eGastrointestinal bleeding\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e3(5%)\u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0 \u003c/p\u003e\n\u003c/td\u003e\t\u003ctd\u003e\u003cp\u003e0.24 \u003c/p\u003e\n\u003c/td\u003e\u003c/tr\u003e\n\u003c/tbody\u003e\u003c/table\u003e\n\u003cp\u003eData are median (quartiles) or number (%). \u003c/p\u003e\n\u003cp\u003e\u003ca name=\"OLE_LINK22\"/\u003e\u003ca name=\"OLE_LINK23\"/\u003eICU, intensive care unit; IABP, intra-aortic balloon pump; ECMO, extracorporeal membrane oxygenation; RIPC, remote ischemic preconditioning; RIPostC, remote ischemic postconditioning.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"ischemia; preconditioning; postconditioning; heart transplantation","lastPublishedDoi":"10.21203/rs.2.182/v3","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.182/v3","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Background\n\nCardioprotective effect of remote ischemic preconditioning (RIPC) in cardiovascular surgery is controversy. This study investigated whether RIPC combined with remote ischemic postconditioning (RIPostC) reduces myocardial injury on donor hearts in patients undergoing heart transplantation.\n\nMethods\n\nOne hundred and twenty patients scheduled for orthotopic heart transplantation were enrolled and randomly assigned to an RIPC+RIPostC group (n=60) or a control (n=60) group. In the RIPC+RIPostC group, four cycles of 5-min ischemia and 5-min reperfusion were applied on the right upper limb by a cuff inflated to 200mmHg after anesthesia induction (RIPC) and 20 minutes after aortic declamping (RIPostC). Serum cardiac troponin I (cTnI) level was determined preoperatively and at 3, 6, 12, 24 h after aortic declamping. Postoperative clinical outcomes were recorded. The primary endpoint was comparison of the cTnI levels at 6 h after aortic declamping.\n\nResults\n\nCompare with the preoperative baseline, serum cTnI levels peaked at 6h after aortic declamping in two groups. Compare with the control group, RIPC+RIPostC significantly reduced the serum cTnI levels at 6h after aortic declamping (38.87±31.81 vs 69.30±34.13ng/ml, P=0.018). There was no significant difference in in-hospital morbidity and mortality between the two groups.\n\nConclusion\n\nIn patients undergoing orthotopic heart transplantation, RIPC combined with RIPostC reduced myocardial injury at 6h after aortic declamping,while we found no evidence of this function provided by RIPC+RIPostC could improve clinical outcomes","manuscriptTitle":"Cardioprotective Effect of Remote Ischemic Preconditioning with Postconditioning on Donor Hearts in Patients Undergoing Heart Transplantation: a single-center, double-blind, randomized controlled trial","msid":"","msnumber":"","nonDraftVersions":[{"code":3,"date":"2019-03-25 14:50:34","doi":"10.21203/rs.2.182/v3","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accept","date":"2019-03-22T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2019-03-21T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2019-03-20T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2019-01-07T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":2,"date":"2019-03-18 19:21:42","doi":"10.21203/rs.2.182/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2019-03-18T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2019-03-15T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2019-03-15T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2019-01-07T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2019-01-08 13:07:40","doi":"10.21203/rs.2.182/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2019-01-23T12:00:00+00:00","index":2,"fulltext":"Form responses:\r\n---\r\n* Are the methods appropriate and well described? **Yes**\r\n* Does the work include the necessary controls? **Yes**\r\n* Are the conclusions drawn adequately supported by the data shown? **Yes**\r\n* Statistical review: **I am able to assess the statistics**\r\n* Quality of written English: **Acceptable**\r\n* Declaration of competing interests: **No conflicts of interest**\r\n\r\nComments to Author:\r\n---\r\n\r\nThe present study is the first demonstration of the effectiveness of RIPC combined with RIPostC in patients undergoing orthotopic heart transplantation. It is an original study that for the first time has been involved in heart transplants with a considerable number of patients. The results presented are in line with the data provided by the literature also of the most recent trials and therefore confirm the hypotheses up to now. The cardiac troponin I difference is in line with what has been supported so far. I think it is an important contribution for those who are interested in preconditioning also because it highlights the possible mechanism of preconditioning linked to the presence of humoral factors responsible for the mechanism. Moreover the analysis of secondary outcomes seems to me very accurate.\r\nAs regards table 1, I consider it useful to insert the value of statistical significativity (p value). \r\nFinally I think it is necessary to update the bibliography with more recent articles about preconditioning."},{"type":"decision","content":"Revise","date":"2019-01-23T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-01-16T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2019-01-12T12:00:00+00:00","index":1,"fulltext":"Form responses:\r\n---\r\n* Are the methods appropriate and well described? **Yes**\r\n* Does the work include the necessary controls? **Yes**\r\n* Are the conclusions drawn adequately supported by the data shown? **No**\r\n* Statistical review: **I am able to assess the statistics**\r\n* Quality of written English: **Not suitable for publication unless extensively edited**\r\n* Declaration of competing interests: **I declare that I have no competing interests**\r\n\r\nComments to Author:\r\n---\r\n\r\nI have several concerns with this submission. First and foremost, significant improvements in the written English are needed throughout the entire manuscript. The impact of many sentences are lost due to inaccuracies in the translation. A significant review of the translation and rewrite would strengthen this manuscript tremendously.\r\n\r\nSecond, I'm not sure the conclusions the authors drew can be entirely contributed to the intervention. Volatile anesthetics have been shown to afford similar preconditioning effects. The authors mention that sevoflurane was used \"as needed\" during line placement. Likewise, the use of propofol may attenuate preconditioning effects. The use of volatile anesthetics should have been standardized as a part of the study protocol; ideally avoiding their use entirely. Since this was not done, the use of sevoflurane should be listed in Table 2. I'd also like to see the intraoperative use of inotropes in this table. Presumably all transplant patients received inotropes post bypass, but it would be interesting to see if there is a statistically significant difference in dose or number of inotropes required. If the intervention had a significant effect on myocardial protection, the intervention group may have a lower inotrope requirement.\r\n\r\nThird, there is no p-value listed in Table 1 and there are clearly statistically significant differences between the groups. Most notably the preoperative use of inotropes was significantly higher in the control group. One could argue that this could increase myocardial work, oxygen consumption, and potentially myocardial damage (despite the fact that troponin was measured in the transplanted heart 6 hours post op). I would include p-values in this table and address any significant differences that are found."},{"type":"reviewerAgreed","content":"","date":"2019-01-10T12:00:00+00:00","index":1,"fulltext":""},{"type":"checksComplete","content":"","date":"2019-01-07T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2019-01-07T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2019-01-07T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2019-01-07T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9709d042-5639-4b96-adac-0b4b233cb98c","owner":[],"postedDate":"March 25th, 2019","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":1043,"name":"Internal Medicine Specialties"}],"tags":[],"updatedAt":"","versionOfRecord":{"articleIdentity":"rs-182","link":"https://link.springer.com/article/10.1186/s12871-019-0720-z","journal":{"identity":"bmc-anesthesiology","isVorOnly":false,"title":"BMC Anesthesiology"},"publishedOn":"2019-04-06 12:00:00","publishedOnDateReadable":"April 6th, 2019"},"versionCreatedAt":"2019-03-25 14:50:34","video":"","vorDoi":"https://link.springer.com/article/10.1186/s12871-019-0720-z","vorDoiUrl":"https://link.springer.com/article/10.1186/s12871-019-0720-z","workflowStages":[]},"version":"v3","identity":"rs-182","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-182","version":["v3"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}