Acoustic Softening in Human Blood Induced by Microbubble Dynamics Under Decompression: Implications for Sudden Cardiac Collapse

Acoustic Softening in Human Blood Induced by Microbubble Dynamics Under Decompression: Implications for Sudden Cardiac Collapse | 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 Physical Sciences - Article Acoustic Softening in Human Blood Induced by Microbubble Dynamics Under Decompression: Implications for Sudden Cardiac Collapse V R Sanal Kumar, Pradeep Kumar Radhakrishnan, Dhruv Panchal, Dekkala Vinay, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9254931/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Sudden cardiac arrest (SCA) in individuals without structural or electrical abnormalities remains an unresolved clinical problem. Here we report a pilot translational study investigating whether pressure-driven microbubble dynamics in human blood can generate physical conditions capable of destabilizing cardiovascular flow. Venous blood from healthy adult volunteers (n = 10) was subjected to controlled decompression (760→100 mmHg) at physiological temperature (37–40 °C), while high-speed imaging quantified microbubble nucleation, growth, coalescence and rupture. Microbubble formation consistently initiated below ~600 mmHg, followed by coalescence into transient gas cavities resembling vapor-lock structures. Increasing void fraction was associated with pronounced acoustic softening, with modeled effective sound speed decreasing from ~1500 m s⁻¹ to <100 m s⁻¹. Surface roughness significantly increased nucleation density (p < 0.05). Bubble rupture events produced localized transient pressure disturbances. Although bulk flow was not imposed, the observed acoustic-softening regime defines mechanical conditions permissive for multiphase flow choking in dynamic systems. These findings establish mechanistic feasibility for a physics-based cascade linking decompression-induced microbubble dynamics, acoustic softening and potential flow instability, motivating future in vivo and dynamic investigations into unexplained sudden cardiac collapse. Physical sciences/Engineering/Biomedical engineering Biological sciences/Physiology/Cardiovascular biology/Cardiovascular diseases/Heart failure Health sciences/Risk factors Sudden cardiac arrest Microbubble nucleation Acoustic softening Sanal flow choking Vapor lock Shock-wave endothelial injury Figures Figure 1 Figure 2 Figure 3 Key Points Sudden cardiac arrest (SCA) in apparently healthy individuals often occurs without identifiable structural, electrical, or thrombotic abnormalities. In this pilot translational study, we demonstrate that pressure-driven microbubble dynamics in human blood can produce vapor-lock–like gas cavities, profound acoustic softening, and physical conditions permissive for multiphase flow choking. These findings establish mechanistic feasibility linking decompression physiology and cardiovascular instability, motivating future powered, dynamic, and in-vivo investigations. Impact Statement Sudden cardiac arrest in individuals without structural heart disease remains an unresolved clinical challenge. Existing paradigms inadequately explain collapse in young and otherwise healthy individuals exposed to extreme physiological or environmental stress. This pilot translational study identifies a physics-based mechanistic cascade linking decompression-driven microbubble dynamics, acoustic softening, and theoretical flow instability. By establishing mechanistic feasibility rather than clinical incidence, this work provides a foundation for future studies aimed at prediction, prevention, and device optimization. Structured Abstract Background Many cases of sudden cardiac arrest (SCA) occur in individuals with normal coronary arteries and no detectable structural or electrical abnormalities, leaving the underlying mechanisms unresolved. This pilot translational study examined whether pressure-driven microbubble dynamics can generate physical conditions capable of destabilizing cardiovascular flow. Methods Venous blood from healthy adult volunteers (n=10; age 24–32 years) was subjected to controlled static decompression (760→100mmHg) at physiological temperature (37–40°C). High-speed imaging quantified microbubble nucleation, growth, coalescence, and rupture. Smooth and rough metallic substrates represented vascular and biomaterial interfaces. Acoustic behavior was analyzed using Wood’s equation to estimate sound-speed reduction and identify acoustic-softening thresholds associated with theoretical multiphase flow choking. Effect sizes and confidence intervals were calculated for key comparisons. Results Microbubble nucleation consistently began below ~600 mmHg, followed by bubble growth, coalescence, and formation of vapor-lock–like gas cavities. Increasing void fraction produced strong acoustic softening, with modeled effective sound speed decreasing from ~1500 m/s to <100 m/s. Rough surfaces exhibited significantly greater nucleation density than smooth surfaces (p < 0.05; large effect size). Bubble rupture generated transient shock-like disturbances. Although bulk flow was not imposed, the acoustic-softening minimum indicates mechanical conditions permissive for multiphase flow choking in dynamic systems. Conclusions These results demonstrate the physical feasibility of a cascade linking decompression-induced microbubble dynamics, acoustic softening, and potential flow instability. The findings are hypothesis-generating and motivate future dynamic and in-vivo studies evaluating relevance to unexplained sudden cardiac arrest. Significance Statement This pilot study proposes a physics-based framework linking microbubble dynamics to acoustic softening and flow instability in blood, motivating future research on monitoring, prevention, and cardiovascular device design for unexplained sudden cardiac collapse. Introduction Sudden cardiac arrest (SCA) remains a leading cause of death worldwide and frequently occurs without warning in individuals who lack structural heart disease, obstructive coronary lesions, or identifiable electrophysiological abnormalities. Despite extensive investigation, the underlying mechanism remains unclear in a substantial proportion of cases, particularly among young and apparently healthy individuals such as elite athletes, aviators, divers, astronauts, and perioperative patients experiencing rapid hemodynamic or ambient pressure transitions. These observations suggest that nontraditional, physics-based mechanisms may contribute to cardiovascular instability under extreme physiological or environmental stress. Recent advances in cardiovascular decompression research have suggested that pressure-induced microbubble dynamics may alter blood flow behavior in ways not captured by conventional embolic or electrophysiologic paradigms [1–5]. Multiphase flow studies in biomedical and aerospace contexts indicate that decompression can promote heterogeneous bubble nucleation, bubble growth, and gas–liquid interactions capable of modifying local mechanical and acoustic properties of fluid systems [1–7]. In particular, prior work has proposed that microbubble expansion may give rise to vapor-lock–like gas cavities, profound acoustic softening, and conditions theoretically permissive for multiphase flow choking, a limit state in which mass flux becomes weakly dependent on downstream pressure [1–7]. These concepts are grounded in classical compressible-flow and acoustic theory but have not been systematically explored in cardiovascular contexts [8-10]. Supporting physiological and engineering observations reinforce the plausibility of this framework, including animal-model reports of vascular deformation following gas embolism [7], aerospace-based modeling of cavitation and shock formation in compliant conduits [10], and clinical observations linking decompression and hemodynamic stress to neurological and cardiovascular events [8-11]. Classical bubble-physics models further support the role of heterogeneous nucleation and acoustic instability under reduced-pressure conditions [12,13]. Collectively, these findings motivate investigation of whether decompression-induced microbubble dynamics can generate mechanical conditions capable of destabilizing cardiovascular flow, even in the absence of structural disease [5,14,15]. Accordingly, the present study was designed as a pilot, hypothesis-generating translational investigation to isolate and characterize the fundamental physical behavior of microbubbles in human blood under controlled decompression. Rather than replicate physiological circulation or establish clinical causality, the objective was to determine whether decompression alone can produce vapor-lock–like gas structures, acoustic softening, and theoretical flow-instability conditions that may warrant further dynamic, in-vivo, and clinical evaluation. By establishing mechanistic feasibility, this work aims to provide a foundational framework for future studies of unexplained sudden cardiac collapse. Methods Study Design and Sample Preparation This investigation was conducted as a pilot, hypothesis-generating translational study designed to characterize pressure-driven microbubble behavior in human blood under controlled static conditions. Fresh venous blood samples were collected from healthy adult volunteers (n = 10; age range 24–32 years) after obtaining written informed consent. All procedures complied with institutional ethical standards for non-interventional blood sampling. Samples were placed in a temperature-controlled vacuum chamber and subjected to static decompression from 760 to 100 mmHg at physiological temperature (37–40 °C). No external pump, perfusion system, or flow loop was employed; blood flow was intentionally not simulated. This design was chosen to isolate fundamental decompression-driven bubble dynamics without confounding influences from shear stress, pulsatility, or vascular compliance. High-Speed Imaging and Bubble Quantification Microbubble nucleation, growth, coalescence, and rupture were recorded using high–frame-rate videography captured with commercially available smartphone cameras. The imaging approach provided sufficient temporal resolution to visualize bubble emergence, growth, coalescence, and rupture events under the experimental conditions. Quantitative analyses focused on determination of nucleation onset pressure, bubble size evolution, coalescence density, and rupture-associated morphological signatures. All analyses were performed under identical decompression protocols across samples. Biomaterial Surface Modeling To assess the influence of surface microtopography on bubble behavior, stainless-steel coupons with smooth and rough finishes were introduced into the experimental chamber. Each blood sample was exposed to both surface conditions under identical decompression profiles, enabling within-sample comparisons rather than randomized group assignments. These surfaces were selected to approximate vascular and biomaterial interfaces relevant to cardiovascular devices. Order of exposure to smooth and rough surfaces was randomized, and image analysis was performed blinded to surface condition. Acoustic Modeling Effective sound speed reduction associated with increasing gas void fraction was estimated using Wood’s equation, a validated physics-based model for multiphase mixtures. Modeled sound speed–void fraction relationships were used to identify acoustic-softening thresholds and mechanical conditions theoretically permissive for multiphase Sanal flow choking in dynamic systems. Because the model is deterministic rather than empirically fitted, validation focused on sensitivity across physiologically relevant pressure and void-fraction ranges rather than statistical goodness-of-fit metrics. Sensitivity analysis varying void fraction and pressure within physiologic ranges changed predicted sound speed by <15%, confirming model robustness. Statistical Analysis Given the pilot nature of the study, no a priori power calculation was performed. Statistical analyses focused on estimating effect magnitude and mechanistic consistency rather than population-level inference. Comparisons of microbubble nucleation density between surface conditions were conducted using paired Student’s t-tests and ANOVA, with statistical significance defined as p < 0.05. Effect sizes (Cohen’s d) and 95% confidence intervals were calculated for primary comparisons. Because analyses were limited to predefined mechanistic hypotheses, formal family-wise error correction was not applied. A post-hoc power analysis indicated that with n = 10 paired samples, the study had approximately 80% power to detect large effect sizes (Cohen’s d ≥ 0.9). Results Microbubble nucleation reproducibly initiated below approximately 600 mmHg during static decompression of venous blood ( Figures 1 and 2 ). As pressure decreased, bubbles enlarged and coalesced, forming elongated cavities and vapor-lock–like gas structures. High–frame-rate videography demonstrated transient obstruction zones in which localized regions became gas-dominant, despite the absence of imposed bulk flow. Bubble rupture events were associated with abrupt morphological transitions and micro-jet–like ejections, producing transient shock-like disturbances. These observations suggest a potential mechanical mechanism by which bubble dynamics could contribute to endothelial or microvascular perturbation under in-vivo conditions. Surface microtopography exerted a significant influence on bubble behavior. Microbubble nucleation occurred earlier and with greater density adjacent to rough, threaded substrates compared with polished smooth surfaces (p < 0.05), consistent with heterogeneous nucleation theory. The magnitude of this difference was large, indicating a strong mechanistic effect of surface features despite the pilot sample size. Acoustic modeling using Wood’s equation demonstrated an orders-of-magnitude reduction in effective mixture sound speed with increasing gas void fraction, decreasing from near-physiologic values (~1500 m/s) into the 10–100 m/s acoustic-softening range. Within this window, multiphase blood transitions toward highly compressible behavior. Extended modeling revealed a characteristic softening–hardening U-shaped relationship between sound speed and void fraction ( Figure 3 ), with the mixture sound speed reaching a minimum at intermediate void fractions before increasing toward gas-phase values (~330 m/s). Although bulk flow was not imposed and mass flux was not directly measured, the acoustic-softening minimum identifies mechanical conditions under which multiphase Sanal flow choking is theoretically permitted in flowing systems, where mass transport becomes weakly dependent on downstream pressure and potentially vulnerable to abrupt destabilization. Discussion Sudden cardiac arrest (SCA) in individuals with structurally normal hearts remains a persistent challenge in cardiovascular medicine, with many events occurring in the absence of thrombotic obstruction, plaque rupture, or identifiable electrophysiologic abnormalities. In this pilot, proof-of-concept investigation, we demonstrate that decompression-induced microbubble formation in human venous blood can generate a reproducible sequence of physical phenomena—microbubble nucleation, vapor-lock–like gas cavity formation, acoustic softening, and shock-like rupture—revealing fundamental mechanical conditions that may predispose to abrupt circulatory destabilization independent of coronary occlusion. These findings suggest that blood exposed to reduced pressure can transition from an effectively incompressible liquid to a highly compressible multiphase system, providing a physics-based mechanistic framework that integrates aerospace decompression physiology with cardiovascular translational science. Importantly, this work is intentionally framed as a pilot translational study, establishing mechanistic feasibility rather than clinical incidence or outcome prediction. These results should be viewed as hypothesis-generating and suggest a possible mechanistic pathway requiring validation in dynamic flow-loop, animal, and clinical studies. A key observation was the emergence of an acoustic-softening window, in which modeled effective sound speed decreased from near-physiologic values (~1500 m/s) to below 100 m/s. Within this range, blood exhibits markedly reduced stiffness and increased compressibility. Wood’s-equation modeling further demonstrated a characteristic softening–hardening U-shaped relationship between sound speed and gas void fraction, with sound speed reaching a minimum within the 10–100 m/s range before increasing toward gas-phase values. The minimum of this curve defines a mechanical condition under which multiphase Sanal flow choking is theoretically permitted in flowing systems, consistent with compressible-flow principles in which mass flux becomes weakly dependent on downstream pressure. Although bulk flow was not imposed and choking was not directly measured in this study, identification of this acoustic-softening minimum provides a foundational basis for future investigations of choking-limited mass transport under dynamic cardiovascular conditions. High–frame-rate videography revealed micro-jet–like ejections and transient shock-like disturbances during bubble rupture, suggesting a potential mechanism for localized endothelial or microvascular perturbation. While direct vascular injury was not assessed, these observations are consistent with prior experimental and theoretical work indicating that rapid bubble dynamics can generate concentrated mechanical stresses. In addition, surface microtopography exerted a pronounced influence on bubble behavior, with significantly earlier and denser nucleation observed on rough interfaces compared with smooth surfaces (p < 0.05). This finding highlights the potential role of biomaterial surface features—including stent strut geometry, graft textures, and surgical hardware—in modulating susceptibility to pressure-dependent bubble phenomena. Although static in-vitro experiments do not reproduce the full complexity of cardiovascular physiology, the present design intentionally isolated the core physical mechanisms governing bubble formation and acoustic transitions without confounding influences such as pulsatility, shear stress, or vessel compliance. This approach is consistent with established practices in multiphase fluid mechanics and acoustic science, where physical feasibility is first established under controlled conditions before dynamic or in-vivo validation. By defining reproducible trigger thresholds and a characteristic acoustic–mechanical profile, this pilot study lays the groundwork for subsequent flow-loop experiments, computational modeling, animal studies, and clinical observational investigations. Thus, rather than limiting translational relevance, the static proof-of-concept format strengthens mechanistic clarity and provides a rational foundation for future cardiovascular risk stratification and prevention strategies. Mechanistic Interpretation The findings of this pilot study are consistent with the following mechanistic cascade: Microbubble nucleation under reduced pressure Bubble expansion and coalescence Formation of vapor-lock–like gas cavities Acoustic softening with marked reduction in effective sound speed Mechanical conditions permissive for multiphase Sanal flow choking Localized shock-like disturbances with potential vascular impact Abrupt circulatory destabilization This hypothesis-generating framework provides a plausible physical explanation for sudden collapse in high-stress environments and clinical settings involving rapid pressure transitions, including aviation, diving, spaceflight, high-performance athletics, cardiopulmonary bypass (CPB), and vacuum-assisted circulation (VAC) systems. Translational Outlook and Relevance This hypothesis-generating mechanistic framework may help explain unexplained sudden cardiac arrest and circulatory instability in individuals exposed to rapid pressure transitions or extreme hemodynamic conditions, including elite athletes, aviators, divers, astronauts, and perioperative patients undergoing extracorporeal circulation or vacuum-assisted drainage. By identifying physical conditions under which blood may become mechanically and acoustically unstable, the findings motivate translational research directions aimed at improving risk assessment, monitoring, and device design. Future investigations should focus on: Quantifying gas void fraction and pressure thresholds under in-vivo conditions Validating the proposed mechanisms in relevant animal models Identifying physiologic and biomaterial features that modulate susceptibility Developing non-invasive acoustic or vibration-based monitoring tools capable of detecting acoustic-softening windows and flow-instability risk states in real time Potential translational applications include: Biomaterial and device-surface engineering strategies to reduce surface-seeded microbubble nucleation Decompression, perfusion, and extracorporeal-circulation protocols optimized to avoid acoustic-softening regimes Acoustic biomarker–based surveillance approaches for early detection and prevention of circulatory destabilization With focused interdisciplinary collaboration, these efforts could inform clinically relevant validation pathways over a multi-year translational horizon. Clinical validation will require stepwise investigation including flow-loop studies, animal models, and prospective clinical registries. The proposed mechanism is complementary to established causes of SCA such as channelopathies and myocarditis, and may be relevant in cases where conventional evaluation is unrevealing. Future Directions Next-phase investigations will build on these pilot findings through a stepwise translational approach, including: (1) closed-loop flow systems to directly examine mass-transport behavior under acoustic-softening conditions; (2) multiphase computational modeling to explore the influence of geometric, rheologic, and physiologic boundary conditions; (3) in-vivo studies to assess hemodynamic and endothelial responses to decompression-induced bubble dynamics; and (4) clinical observational studies designed to correlate pressure transitions, acoustic signatures, and episodes of circulatory instability. Together, these efforts will help determine whether identifying and avoiding acoustic-softening and flow-instability regimes may inform future risk stratification strategies in high-hazard populations. Final Synthesis This pilot translational study demonstrates that decompression-induced microbubble dynamics can place blood into an acoustically softened and mechanically altered regime under controlled conditions. These findings support the feasibility of a physics-based framework in which multiphase flow behavior, rather than thrombotic obstruction or primary electrical failure, may contribute to circulatory destabilization in selected settings. By establishing mechanistic plausibility and defining testable physical conditions, this work provides a foundation for coordinated experimental, computational, and clinical investigations aimed at improving understanding, risk stratification, and device design related to unexplained sudden cardiac arrest. Limitations This study has limitations consistent with its pilot design. First, the sample size was intentionally small and not powered for population-level inference; accordingly, the findings should be interpreted as hypothesis-generating. Second, experiments were conducted under static decompression conditions without imposed blood flow, precluding direct measurement of choking-limited mass transport. Third, acoustic softening and flow-instability conditions were inferred from validated physical models rather than directly measured in vivo. Finally, individual susceptibility factors and clinical correlates were not evaluated. Collectively, these limitations motivate ongoing and future investigations using dynamic flow-loop systems, animal models, and clinical observational studies. The study was powered only to detect large mechanistic effects. Conclusion Unexplained sudden cardiac arrest may, in selected settings, involve decompression-driven microbubble dynamics that promote vapor-lock–like gas formation, acoustic softening, and flow-instability conditions consistent with multiphase Sanal flow choking. By establishing the mechanistic feasibility of this physics-based cascade in human blood, this pilot study offers a unifying hypothesis for sudden circulatory collapse in otherwise healthy individuals and provides a rational foundation for future translational efforts aimed at improved risk stratification, monitoring, and device design. These findings suggest a possible mechanistic pathway requiring further validation before clinical inference. Declarations Acknowledgments The authors gratefully acknowledge the American Heart Association for conferring the 2025 Paul Dudley International Scholar Award in connection with our best abstract presented at the BCVS 2025 Scientific Sessions. We thank the American Heart Association, the American Institute of Aeronautics and Astronautics (AIAA) and the NASA Human Research Program Investigators’ Workshop for providing platforms to disseminate related aspects of this work. The first author acknowledges support from the Government of India, India–U.S. research collaborators, and Dr. W. Selvamurthy, Amity University, for institutional and project support under the DST–Amity–TEC initiative. Disclosures: An AI tool was used to assist with text condensation. Authors’ contributions VRSK conceptualized and designed the study. PKR contributed to the conceptual framework, while DP led the in vitro experiments and data analysis. DV and YR were responsible for designing the in vitro study. RS , YV , and SR participated in conducting the in vitro experiments, and SS provided in vitro and funding support. All listed authors have reviewed and approved this study for publication. Corresponding author Correspondence to V.R.S.Kumar: [email protected] / [email protected] Materials and Methods: In vitro method. Data availability statement: The data that support the findings of this study are available within the article. Conflict of Interest The authors report no conflicts of interest relevant to this manuscript, with the exception of pending related patent applications in India. Ethics approval: Approved by Institutional Ethics Committee of Amity Institute of Aerospace Engineering, Amity University Uttar Pradesh (Approval No. DST-Amity-TEC-AIAE/VRS/P1_477/2025) Informed consent statement: Written informed consent was obtained from all participants. Funding: Department of Science and Technology (DST), Government of India (Amity University Technology Enabling Centre - Project Code: AUUP/2019/477), DST-Amity-TEC project No. AUUP/AIAE/VRS/ P1/2023–2025). References Sanal Kumar VR, Radhakrishnan PK, Panchal D, et al. In vitro evidence of bubble-induced acoustic softening and Sanal flow choking in cardiovascular decompression. npj Microgravity . 2025;11(54). doi:10.1038/s41526-025-00517-5 Sanal Kumar VR, Radhakrishnan PK, Panchal D, et al. Microbubble-Induced Shock Waves in Blood: Investigating Multiphase Sanal Flow Choking During Decompression. Circ Res . 2025;137(Suppl_1):Fri015. https://www.ahajournals.org/doi/abs/10.1161/res.137.suppl_1.Fri015 Sanal Kumar VR, Choudhary SK, Radhakrishnan PK, Anbu J, Deveswaran R, Bharath S, et al. Elevated blood vapor pressure and reduced heat capacity of blood lead to gas embolism causing flow choking in gravity and microgravity environments. NASA Human Research Program Investigators’ Workshop ; February 13–16, 2024. Abstract No. 1646500. Sanal Kumar VR, Radhakrishnan PK. Sanal flow choking in cardiovascular systems is not a scientific fallacy but a groundbreaking concept. Indian J Thorac Cardiovasc Surg . 2024. doi:10.1007/s12055-024-01859-7 Sanal Kumar VR, Panchal D, Sharma R, Vohra YN, Rana S, Dekkala V, Raj Y, Singh S, Radhakrishnan PK. Decompression-induced microbubble choking in blood: acoustic softening, Sanal flow choking, and spaceflight implications. AIAA SciTech 2026 Forum . AIAA Paper No. 2026-0720. Published on January 8, 2026. doi:10.2514/6.2026-0720. Anbu J, Deveswaran R, Bharath S, et al. Animal in vivo proof of flow choking and bulging of stenotic arteries due to air embolism. Circ Res . 2022;131(Suppl_1):P3028. Panchal D, Singh S, Kumar R, Sanal Kumar VR. Microbubble dynamics in hydrocarbon fuels under reduced pressure: Experimental insights into acoustic softening and Sanal flow choking. Appl Therm Eng . 2025;280(Pt 5):128471. doi:10.1016/j.applthermaleng.2025.128471 Sanal Kumar VR. Sanal flow choking leads to hemorrhagic stroke and other neurological disorders in Earth and spaceflight. Circ Res . 2021;129(Suppl_1):P422. Sanal Kumar VR. Lopsided blood-thinning drug increases risk of internal flow choking and shock wave generation causing asymptomatic stroke. Stroke . 2021;52(Suppl_1):P804. Sanal Kumar VR, Sankar V, Chandrasekaran N, et al. Boundary layer blockage, Venturi effect and cavitation causing aerodynamic choking and shock waves in human artery leading to massive heart attack. AIAA Paper . 2018;No. 2018-3962. Herrick JB. Clinical features of sudden obstruction of the coronary arteries. JAMA . 1912;59(23):2015-2022. doi:10.1001/jama.1912.04270120001001 Atchley AA, Prosperetti A. The crevice model of bubble nucleation. J Acoust Soc Am . 1989;86:1065-1074. doi:10.1121/1.398343 Leighton TG. The Acoustic Bubble . Academic Press; 1994. Sanal Kumar, V. R., Choudhary SK, Radhakrishnan PK, et al., Nanoscale Flow Choking and Spaceflight Effects on Cardiovascular Risk of Astronauts – A New Perspective. AIAA SciTech Forum ; 2021. Paper No. AIAA 2021-0357. Published online January 4, 2021. doi:10.2514/6.2021-0357. Sanal Kumar, V. R. et al. Boundary Layer Blockage, Venturi Effect and Cavitation Causing Aerodynamic Choking and Shock Waves in Human Artery Leading to Hemorrhage and Massive Heart Attack—a New Perspective AIAA Paper No 3962. 2018. https://doi.org/10.2514/6.2018-3962 (2018). Additional Declarations There is NO Competing Interest. Supplementary Files GraphicalAbstract.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version 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-9254931","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Physical Sciences - Article","associatedPublications":[],"authors":[{"id":614488328,"identity":"3736cfd5-830e-4b71-a6c1-91378ea0d508","order_by":0,"name":"V R Sanal Kumar","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIiWNgGAWjYBADGQkwVcHAYAAV4SGkhQei5QzJWhjbEFpwAoPbB5g//NxhxyM5Izvxc+W8w/Lm7M0HGH5UMMiY49JyLoFNsvdMMo+0RO5mybPbDhvu7DmWwNhzhoHHsgG7FskeBjYG3jZmHjmJ3A2SjdsOM264kWPADHQhj8EBnFqYP/5tqwdp2fyzcc5he4Ja+IEBI83bdhjksG2SjQ2HE4nRwiYt23acR7Ln7TbLhmPpyRvOHEs42HNGAqcWNh6gw962VctJHM/dfLOhxtp2w/Hmgw9+VNjY49ICtOcDMq8ZTAIVS+BSjwHqiFY5CkbBKBgFIwcAAE7MVLi0W7baAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-5643-7223","institution":"Amity University Uttar Pradesh","correspondingAuthor":true,"prefix":"","firstName":"V","middleName":"R Sanal","lastName":"Kumar","suffix":""},{"id":614488329,"identity":"c6770ef2-afee-4634-b783-ada4c44cb693","order_by":1,"name":"Pradeep Kumar Radhakrishnan","email":"","orcid":"","institution":"Biomexia","correspondingAuthor":false,"prefix":"","firstName":"Pradeep","middleName":"Kumar","lastName":"Radhakrishnan","suffix":""},{"id":614488330,"identity":"29a5aa72-22c0-4edf-91b0-e1fcc1a011cf","order_by":2,"name":"Dhruv Panchal","email":"","orcid":"","institution":"Dhruv Aerospace","correspondingAuthor":false,"prefix":"","firstName":"Dhruv","middleName":"","lastName":"Panchal","suffix":""},{"id":614488331,"identity":"b672ea79-a339-4aba-9cf1-78bb1fee8b51","order_by":3,"name":"Dekkala Vinay","email":"","orcid":"","institution":"Amity Institute of Aerospace Engineering","correspondingAuthor":false,"prefix":"","firstName":"Dekkala","middleName":"","lastName":"Vinay","suffix":""},{"id":614488332,"identity":"1c9ecf95-7e71-4dc6-95dd-f200e175b023","order_by":4,"name":"Yash Raj","email":"","orcid":"","institution":"Amity Institute of Aerospace Engineering, Amity University Uttar Pradesh,","correspondingAuthor":false,"prefix":"","firstName":"Yash","middleName":"","lastName":"Raj","suffix":""},{"id":614488333,"identity":"bd573a0b-1dca-4cc1-86be-e06534676c7c","order_by":5,"name":"Raunak Sharma","email":"","orcid":"","institution":"Amity University","correspondingAuthor":false,"prefix":"","firstName":"Raunak","middleName":"","lastName":"Sharma","suffix":""},{"id":614488334,"identity":"c8527fb2-e5c3-4a41-9c08-1f3732e4fe85","order_by":6,"name":"Yaman Vohra","email":"","orcid":"","institution":"Amity Institute of Aerospace Engineering","correspondingAuthor":false,"prefix":"","firstName":"Yaman","middleName":"","lastName":"Vohra","suffix":""},{"id":614488335,"identity":"57b60df7-420d-45e6-a6fc-be28c97c5a11","order_by":7,"name":"Shivansh Rana","email":"","orcid":"","institution":"Amity Institute of Aerospace Engineering","correspondingAuthor":false,"prefix":"","firstName":"Shivansh","middleName":"","lastName":"Rana","suffix":""},{"id":614488336,"identity":"fc3f011b-b10a-4cc2-af15-8b479e17f92d","order_by":8,"name":"Sanjay Singh","email":"","orcid":"","institution":"Amity Institute of Aerospace Engineering, Amity University Uttar Pradesh","correspondingAuthor":false,"prefix":"","firstName":"Sanjay","middleName":"","lastName":"Singh","suffix":""}],"badges":[],"createdAt":"2026-03-28 19:25:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9254931/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9254931/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105882837,"identity":"1061d023-c041-4e41-8f30-c0ef1dcb5fe9","added_by":"auto","created_at":"2026-04-01 07:01:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":498235,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMicrobubble nucleation diversity in decompressed venous blood under controlled static pressure reduction. \u003c/strong\u003eHigh-magnification images of venous blood samples from healthy volunteers exposed to decompression (760→100 mmHg, 40 °C) demonstrate distinct microbubble nucleation patterns and morphology. Variability in bubble density, spatial distribution, and coalescence behavior reflects heterogeneity in microstructural interfaces and gas-seeding surfaces. Clustered and peripheral accumulations indicate different void-fraction evolution pathways that may progress toward vapor-lock–like gas pockets and conditions permissive for acoustic softening and multiphase Sanal flow choking. These findings establish foundational mechanistic evidence supporting decompression-induced bubble dynamics as a potential trigger for sudden circulatory collapse in structurally normal hearts.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9254931/v1/b906f07a8e10e7d653d4ec92.png"},{"id":105882836,"identity":"37971c3d-d5b3-4a81-bfc9-443f4c895afb","added_by":"auto","created_at":"2026-04-01 07:01:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":234638,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSequential morphological transitions in a single venous blood specimen during decompression.\u003c/strong\u003eRepresentative images of the same sample during controlled vacuum decompression (760→100 mmHg, 40 °C). Stages include bubble emergence, localized vaporization, protein polymerization, and crust formation with brittle crystalline edges. These transitions reflect dynamic bubble activity and phase change phenomena that culminate in vapor lock and acoustic softening, predisposing blood flow to Sanal flow choking and vascular shock-wave formation.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-9254931/v1/7d965fd12903efac5ffd30a4.png"},{"id":105882839,"identity":"acafaff9-3b70-407e-a93d-cfe93cc966e7","added_by":"auto","created_at":"2026-04-01 07:01:55","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":77841,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAcoustic softening in blood–air mixtures modeled using Wood’s equation. \u003c/strong\u003eEffective sound speed \u003cem\u003ec \u003c/em\u003e\u003csub\u003e\u003cem\u003emix\u003c/em\u003e\u003c/sub\u003e\u003cem\u003e (α,P)\u003c/em\u003e \u0026nbsp;\u0026nbsp;versus gas void fraction α for physiological static intravascular pressures 30–150 mmHg (log y-axis). All curves begin at ~1500 m/s, the normal arterial sound speed (α≈0), and collapse sharply into the 10–100 m/s range at modest void fractions due to acoustic softening. Lower pressures exhibit deeper minima, demonstrating pressure dependence of the softening window and the conditions that promote Sanal flow choking.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9254931/v1/53f0b7abad5bc729e111c94c.png"},{"id":106401813,"identity":"9d19dfa4-eda3-48a4-9cee-cdb9e95f8ef8","added_by":"auto","created_at":"2026-04-08 09:09:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1700122,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9254931/v1/002e028a-7af2-4125-908d-98216886e5a0.pdf"},{"id":105882838,"identity":"7e8ee83e-0896-41a8-8f7b-441c638821bd","added_by":"auto","created_at":"2026-04-01 07:01:55","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":3174405,"visible":true,"origin":"","legend":"","description":"","filename":"GraphicalAbstract.docx","url":"https://assets-eu.researchsquare.com/files/rs-9254931/v1/69b5bdd236bc3b2c3e397e48.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Acoustic Softening in Human Blood Induced by Microbubble Dynamics Under Decompression: Implications for Sudden Cardiac Collapse","fulltext":[{"header":"Key Points","content":"\u003cul\u003e\n \u003cli\u003eSudden cardiac arrest (SCA) in apparently healthy individuals often occurs without identifiable structural, electrical, or thrombotic abnormalities.\u003c/li\u003e\n \u003cli\u003eIn this pilot translational study, we demonstrate that pressure-driven microbubble dynamics in human blood can produce vapor-lock–like gas cavities, profound acoustic softening, and physical conditions permissive for multiphase flow choking.\u003c/li\u003e\n \u003cli\u003eThese findings establish mechanistic feasibility linking decompression physiology and cardiovascular instability, motivating future powered, dynamic, and in-vivo investigations.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Impact Statement","content":"\u003cp\u003eSudden cardiac arrest in individuals without structural heart disease remains an unresolved clinical challenge. Existing paradigms inadequately explain collapse in young and otherwise healthy individuals exposed to extreme physiological or environmental stress. This pilot translational study identifies a physics-based mechanistic cascade linking decompression-driven microbubble dynamics, acoustic softening, and theoretical flow instability. By establishing mechanistic feasibility rather than clinical incidence, this work provides a foundation for future studies aimed at prediction, prevention, and device optimization.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Structured Abstract","content":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMany cases of sudden cardiac arrest (SCA) occur in individuals with normal coronary arteries and no detectable structural or electrical abnormalities, leaving the underlying mechanisms unresolved. This pilot translational study examined whether pressure-driven microbubble dynamics can generate physical conditions capable of destabilizing cardiovascular flow.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVenous blood from healthy adult volunteers (n=10; age 24–32 years) was subjected to controlled static decompression (760→100mmHg) at physiological temperature (37–40°C). High-speed imaging quantified microbubble nucleation, growth, coalescence, and rupture. Smooth and rough metallic substrates represented vascular and biomaterial interfaces. Acoustic behavior was analyzed using Wood’s equation to estimate sound-speed reduction and identify acoustic-softening thresholds associated with theoretical multiphase flow choking. Effect sizes and confidence intervals were calculated for key comparisons.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMicrobubble nucleation consistently began below ~600 mmHg, followed by bubble growth, coalescence, and formation of vapor-lock–like gas cavities. Increasing void fraction produced strong acoustic softening, with modeled effective sound speed decreasing from ~1500 m/s to \u0026lt;100 m/s. Rough surfaces exhibited significantly greater nucleation density than smooth surfaces (p \u0026lt; 0.05; large effect size). Bubble rupture generated transient shock-like disturbances. Although bulk flow was not imposed, the acoustic-softening minimum indicates mechanical conditions permissive for multiphase flow choking in dynamic systems.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThese results demonstrate the physical feasibility of a cascade linking decompression-induced microbubble dynamics, acoustic softening, and potential flow instability. The findings are hypothesis-generating and motivate future dynamic and in-vivo studies evaluating relevance to unexplained sudden cardiac arrest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSignificance Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis pilot study proposes a physics-based framework linking microbubble dynamics to acoustic softening and flow instability in blood, motivating future research on monitoring, prevention, and cardiovascular device design for unexplained sudden cardiac collapse.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eSudden cardiac arrest (SCA) remains a leading cause of death worldwide and frequently occurs without warning in individuals who lack structural heart disease, obstructive coronary lesions, or identifiable electrophysiological abnormalities. Despite extensive investigation, the underlying mechanism remains unclear in a substantial proportion of cases, particularly among young and apparently healthy individuals such as elite athletes, aviators, divers, astronauts, and perioperative patients experiencing rapid hemodynamic or ambient pressure transitions. These observations suggest that nontraditional, physics-based mechanisms may contribute to cardiovascular instability under extreme physiological or environmental stress.\u003c/p\u003e\n\u003cp\u003eRecent advances in cardiovascular decompression research have suggested that pressure-induced microbubble dynamics may alter blood flow behavior in ways not captured by conventional embolic or electrophysiologic paradigms [1\u0026ndash;5]. Multiphase flow studies in biomedical and aerospace contexts indicate that decompression can promote heterogeneous bubble nucleation, bubble growth, and gas\u0026ndash;liquid interactions capable of modifying local mechanical and acoustic properties of fluid systems [1\u0026ndash;7]. In particular, prior work has proposed that microbubble expansion may give rise to vapor-lock\u0026ndash;like gas cavities, profound acoustic softening, and conditions theoretically permissive for multiphase flow choking, a limit state in which mass flux becomes weakly dependent on downstream pressure [1\u0026ndash;7]. These concepts are grounded in classical compressible-flow and acoustic theory but have not been systematically explored in cardiovascular contexts [8-10].\u003c/p\u003e\n\u003cp\u003eSupporting physiological and engineering observations reinforce the plausibility of this framework, including animal-model reports of vascular deformation following gas embolism [7], aerospace-based modeling of cavitation and shock formation in compliant conduits [10], and clinical observations linking decompression and hemodynamic stress to neurological and cardiovascular events [8-11]. Classical bubble-physics models further support the role of heterogeneous nucleation and acoustic instability under reduced-pressure conditions [12,13]. Collectively, these findings motivate investigation of whether decompression-induced microbubble dynamics can generate mechanical conditions capable of destabilizing cardiovascular flow, even in the absence of structural disease [5,14,15].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAccordingly, the present study was designed as a pilot, hypothesis-generating translational investigation to isolate and characterize the fundamental physical behavior of microbubbles in human blood under controlled decompression. Rather than replicate physiological circulation or establish clinical causality, the objective was to determine whether decompression alone can produce vapor-lock\u0026ndash;like gas structures, acoustic softening, and theoretical flow-instability conditions that may warrant further dynamic, in-vivo, and clinical evaluation. By establishing mechanistic feasibility, this work aims to provide a foundational framework for future studies of unexplained sudden cardiac collapse.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy Design and Sample Preparation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis investigation was conducted as a pilot, hypothesis-generating translational study designed to characterize pressure-driven microbubble behavior in human blood under controlled static conditions. Fresh venous blood samples were collected from healthy adult volunteers (n = 10; age range 24\u0026ndash;32 years) after obtaining written informed consent. All procedures complied with institutional ethical standards for non-interventional blood sampling.\u003c/p\u003e\n\u003cp\u003eSamples were placed in a temperature-controlled vacuum chamber and subjected to static decompression from 760 to 100 mmHg at physiological temperature (37\u0026ndash;40 \u0026deg;C). No external pump, perfusion system, or flow loop was employed; blood flow was intentionally not simulated. This design was chosen to isolate fundamental decompression-driven bubble dynamics without confounding influences from shear stress, pulsatility, or vascular compliance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHigh-Speed Imaging and Bubble Quantification\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMicrobubble nucleation, growth, coalescence, and rupture were recorded using high\u0026ndash;frame-rate videography captured with commercially available smartphone cameras. The imaging approach provided sufficient temporal resolution to visualize bubble emergence, growth, coalescence, and rupture events under the experimental conditions. Quantitative analyses focused on determination of nucleation onset pressure, bubble size evolution, coalescence density, and rupture-associated morphological signatures. All analyses were performed under identical decompression protocols across samples.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBiomaterial Surface Modeling\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;To assess the influence of surface microtopography on bubble behavior, stainless-steel coupons with smooth and rough finishes were introduced into the experimental chamber. Each blood sample was exposed to both surface conditions under identical decompression profiles, enabling within-sample comparisons rather than randomized group assignments. These surfaces were selected to approximate vascular and biomaterial interfaces relevant to cardiovascular devices. Order of exposure to smooth and rough surfaces was randomized, and image analysis was performed blinded to surface condition.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcoustic Modeling\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Effective sound speed reduction associated with increasing gas void fraction was estimated using Wood\u0026rsquo;s equation, a validated physics-based model for multiphase mixtures. Modeled sound speed\u0026ndash;void fraction relationships were used to identify acoustic-softening thresholds and mechanical conditions theoretically permissive for multiphase Sanal flow choking in dynamic systems. Because the model is deterministic rather than empirically fitted, validation focused on sensitivity across physiologically relevant pressure and void-fraction ranges rather than statistical goodness-of-fit metrics. Sensitivity analysis varying void fraction and pressure within physiologic ranges changed predicted sound speed by \u0026lt;15%, confirming model robustness.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGiven the pilot nature of the study, no \u003cem\u003ea priori\u003c/em\u003e power calculation was performed. Statistical analyses focused on estimating effect magnitude and mechanistic consistency rather than population-level inference. Comparisons of microbubble nucleation density between surface conditions were conducted using paired Student\u0026rsquo;s t-tests and ANOVA, with statistical significance defined as p \u0026lt; 0.05. Effect sizes (Cohen\u0026rsquo;s d) and 95% confidence intervals were calculated for primary comparisons. Because analyses were limited to predefined mechanistic hypotheses, formal family-wise error correction was not applied. A post-hoc power analysis indicated that with n = 10 paired samples, the study had approximately 80% power to detect large effect sizes (Cohen\u0026rsquo;s d \u0026ge; 0.9).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eMicrobubble nucleation reproducibly initiated below approximately 600 mmHg during static decompression of venous blood (\u003cstrong\u003eFigures 1\u0026nbsp;\u003c/strong\u003eand\u003cstrong\u003e\u0026nbsp;2\u003c/strong\u003e). As pressure decreased, bubbles enlarged and coalesced, forming elongated cavities and vapor-lock\u0026ndash;like gas structures. High\u0026ndash;frame-rate videography demonstrated transient obstruction zones in which localized regions became gas-dominant, despite the absence of imposed bulk flow.\u003c/p\u003e\n\u003cp\u003eBubble rupture events were associated with abrupt morphological transitions and micro-jet\u0026ndash;like ejections, producing transient shock-like disturbances. These observations suggest a potential mechanical mechanism by which bubble dynamics could contribute to endothelial or microvascular perturbation under in-vivo conditions.\u003c/p\u003e\n\u003cp\u003eSurface microtopography exerted a significant influence on bubble behavior. Microbubble nucleation occurred earlier and with greater density adjacent to rough, threaded substrates compared with polished smooth surfaces (p \u0026lt; 0.05), consistent with heterogeneous nucleation theory. The magnitude of this difference was large, indicating a strong mechanistic effect of surface features despite the pilot sample size.\u003c/p\u003e\n\u003cp\u003eAcoustic modeling using Wood\u0026rsquo;s equation demonstrated an orders-of-magnitude reduction in effective mixture sound speed with increasing gas void fraction, decreasing from near-physiologic values (~1500 m/s) into the 10\u0026ndash;100 m/s acoustic-softening range. Within this window, multiphase blood transitions toward highly compressible behavior. Extended modeling revealed a characteristic softening\u0026ndash;hardening U-shaped relationship between sound speed and void fraction (\u003cstrong\u003eFigure 3\u003c/strong\u003e), with the mixture sound speed reaching a minimum at intermediate void fractions before increasing toward gas-phase values (~330 m/s).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Although bulk flow was not imposed and mass flux was not directly measured, the acoustic-softening minimum identifies mechanical conditions under which multiphase Sanal flow choking is theoretically permitted in flowing systems, where mass transport becomes weakly dependent on downstream pressure and potentially vulnerable to abrupt destabilization.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eSudden cardiac arrest (SCA) in individuals with structurally normal hearts remains a persistent challenge in cardiovascular medicine, with many events occurring in the absence of thrombotic obstruction, plaque rupture, or identifiable electrophysiologic abnormalities. In this pilot, proof-of-concept investigation, we demonstrate that decompression-induced microbubble formation in human venous blood can generate a reproducible sequence of physical phenomena—microbubble nucleation, vapor-lock–like gas cavity formation, acoustic softening, and shock-like rupture—revealing fundamental mechanical conditions that may predispose to abrupt circulatory destabilization independent of coronary occlusion. These findings suggest that blood exposed to reduced pressure can transition from an effectively incompressible liquid to a highly compressible multiphase system, providing a physics-based mechanistic framework that integrates aerospace decompression physiology with cardiovascular translational science. Importantly, this work is intentionally framed as a pilot translational study, establishing mechanistic feasibility rather than clinical incidence or outcome prediction. These results should be viewed as hypothesis-generating and suggest a possible mechanistic pathway requiring validation in dynamic flow-loop, animal, and clinical studies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e \u0026nbsp;A key observation was the emergence of an acoustic-softening window, in which modeled effective sound speed decreased from near-physiologic values (~1500 m/s) to below 100 m/s. Within this range, blood exhibits markedly reduced stiffness and increased compressibility. Wood’s-equation modeling further demonstrated a characteristic softening–hardening U-shaped relationship between sound speed and gas void fraction, with sound speed reaching a minimum within the 10–100 m/s range before increasing toward gas-phase values. The minimum of this curve defines a mechanical condition under which multiphase Sanal flow choking is theoretically permitted in flowing systems, consistent with compressible-flow principles in which mass flux becomes weakly dependent on downstream pressure. Although bulk flow was not imposed and choking was not directly measured in this study, identification of this acoustic-softening minimum provides a foundational basis for future investigations of choking-limited mass transport under dynamic cardiovascular conditions.\u003c/p\u003e\n\u003cp\u003e \u0026nbsp;High–frame-rate videography revealed micro-jet–like ejections and transient shock-like disturbances during bubble rupture, suggesting a potential mechanism for localized endothelial or microvascular perturbation. While direct vascular injury was not assessed, these observations are consistent with prior experimental and theoretical work indicating that rapid bubble dynamics can generate concentrated mechanical stresses. In addition, surface microtopography exerted a pronounced influence on bubble behavior, with significantly earlier and denser nucleation observed on rough interfaces compared with smooth surfaces (p \u0026lt; 0.05). This finding highlights the potential role of biomaterial surface features—including stent strut geometry, graft textures, and surgical hardware—in modulating susceptibility to pressure-dependent bubble phenomena.\u003c/p\u003e\n\u003cp\u003e Although static in-vitro experiments do not reproduce the full complexity of cardiovascular physiology, the present design intentionally isolated the core physical mechanisms governing bubble formation and acoustic transitions without confounding influences such as pulsatility, shear stress, or vessel compliance. This approach is consistent with established practices in multiphase fluid mechanics and acoustic science, where physical feasibility is first established under controlled conditions before dynamic or in-vivo validation. By defining reproducible trigger thresholds and a characteristic acoustic–mechanical profile, this pilot study lays the groundwork for subsequent flow-loop experiments, computational modeling, animal studies, and clinical observational investigations. Thus, rather than limiting translational relevance, the static proof-of-concept format strengthens mechanistic clarity and provides a rational foundation for future cardiovascular risk stratification and prevention strategies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMechanistic Interpretation\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe findings of this pilot study are \u003cstrong\u003econsistent with\u003c/strong\u003e the following mechanistic cascade:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eMicrobubble nucleation under reduced pressure\u003c/li\u003e\n \u003cli\u003eBubble expansion and coalescence\u003c/li\u003e\n \u003cli\u003eFormation of vapor-lock–like gas cavities\u003c/li\u003e\n \u003cli\u003eAcoustic softening with marked reduction in effective sound speed\u003c/li\u003e\n \u003cli\u003eMechanical conditions permissive for multiphase Sanal flow choking\u003c/li\u003e\n \u003cli\u003eLocalized shock-like disturbances with potential vascular impact\u003c/li\u003e\n \u003cli\u003eAbrupt circulatory destabilization\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eThis hypothesis-generating framework provides a plausible physical explanation for sudden collapse in high-stress environments and clinical settings involving rapid pressure transitions, including aviation, diving, spaceflight, high-performance athletics, cardiopulmonary bypass (CPB), and vacuum-assisted circulation (VAC) systems.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTranslational Outlook and Relevance\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis hypothesis-generating mechanistic framework may help explain unexplained sudden cardiac arrest and circulatory instability in individuals exposed to rapid pressure transitions or extreme hemodynamic conditions, including elite athletes, aviators, divers, astronauts, and perioperative patients undergoing extracorporeal circulation or vacuum-assisted drainage. By identifying physical conditions under which blood may become mechanically and acoustically unstable, the findings motivate translational research directions aimed at improving risk assessment, monitoring, and device design.\u003c/p\u003e\n\u003cp\u003eFuture investigations should focus on:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003eQuantifying gas void fraction and pressure thresholds under in-vivo conditions\u003c/li\u003e\n \u003cli\u003eValidating the proposed mechanisms in relevant animal models\u003c/li\u003e\n \u003cli\u003eIdentifying physiologic and biomaterial features that modulate susceptibility\u003c/li\u003e\n \u003cli\u003eDeveloping non-invasive acoustic or vibration-based monitoring tools capable of detecting acoustic-softening windows and flow-instability risk states in real time\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003ePotential translational applications include:\u003c/p\u003e\n\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003eBiomaterial and device-surface engineering strategies to reduce surface-seeded microbubble nucleation\u003c/li\u003e\n \u003cli\u003eDecompression, perfusion, and extracorporeal-circulation protocols optimized to avoid acoustic-softening regimes\u003c/li\u003e\n \u003cli\u003eAcoustic biomarker–based surveillance approaches for early detection and prevention of circulatory destabilization\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eWith focused interdisciplinary collaboration, these efforts could inform clinically relevant validation pathways over a multi-year translational horizon.\u003c/p\u003e\n\u003cp\u003eClinical validation will require stepwise investigation including flow-loop studies, animal models, and prospective clinical registries.\u003c/p\u003e\n\u003cp\u003eThe proposed mechanism is complementary to established causes of SCA such as channelopathies and myocarditis, and may be relevant in cases where conventional evaluation is unrevealing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFuture Directions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNext-phase investigations will build on these pilot findings through a stepwise translational approach, including: (1) closed-loop flow systems to directly examine mass-transport behavior under acoustic-softening conditions; (2) multiphase computational modeling to explore the influence of geometric, rheologic, and physiologic boundary conditions; (3) in-vivo studies to assess hemodynamic and endothelial responses to decompression-induced bubble dynamics; and (4) clinical observational studies designed to correlate pressure transitions, acoustic signatures, and episodes of circulatory instability. Together, these efforts will help determine whether identifying and avoiding acoustic-softening and flow-instability regimes may inform future risk stratification strategies in high-hazard populations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinal Synthesis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis pilot translational study demonstrates that decompression-induced microbubble dynamics can place blood into an acoustically softened and mechanically altered regime under controlled conditions. These findings support the feasibility of a physics-based framework in which multiphase flow behavior, rather than thrombotic obstruction or primary electrical failure, may contribute to circulatory destabilization in selected settings. By establishing mechanistic plausibility and defining testable physical conditions, this work provides a foundation for coordinated experimental, computational, and clinical investigations aimed at improving understanding, risk stratification, and device design related to unexplained sudden cardiac arrest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study has limitations consistent with its pilot design. First, the sample size was intentionally small and not powered for population-level inference; accordingly, the findings should be interpreted as hypothesis-generating. Second, experiments were conducted under static decompression conditions without imposed blood flow, precluding direct measurement of choking-limited mass transport. Third, acoustic softening and flow-instability conditions were inferred from validated physical models rather than directly measured in vivo. Finally, individual susceptibility factors and clinical correlates were not evaluated. Collectively, these limitations motivate ongoing and future investigations using dynamic flow-loop systems, animal models, and clinical observational studies. The study was powered only to detect large mechanistic effects.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eUnexplained sudden cardiac arrest may, in selected settings, involve decompression-driven microbubble dynamics that promote vapor-lock–like gas formation, acoustic softening, and flow-instability conditions consistent with multiphase Sanal flow choking. By establishing the mechanistic feasibility of this physics-based cascade in human blood, this pilot study offers a unifying hypothesis for sudden circulatory collapse in otherwise healthy individuals and provides a rational foundation for future translational efforts aimed at improved risk stratification, monitoring, and device design. These findings suggest a possible mechanistic pathway requiring further validation before clinical inference.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003cstrong\u003e\u003cbr\u003e\u003c/strong\u003eThe authors gratefully acknowledge the American Heart Association for conferring \u003cem\u003ethe 2025 Paul Dudley International Scholar Award\u003c/em\u003e in connection with our best abstract presented at the BCVS 2025 Scientific Sessions. We thank the American Heart Association, the American Institute of Aeronautics and Astronautics (AIAA) and the NASA Human Research Program Investigators’ Workshop for providing platforms to disseminate related aspects of this work. The first author acknowledges support from the Government of India, India–U.S. research collaborators, and Dr. W. Selvamurthy, Amity University, for institutional and project support under the DST–Amity–TEC initiative.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosures:\u003c/strong\u003eAn AI tool was used to assist with text condensation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVRSK\u003c/strong\u003e conceptualized and designed the study. \u003cstrong\u003ePKR\u003c/strong\u003e contributed to the conceptual framework, while \u003cstrong\u003eDP\u003c/strong\u003e led the in vitro experiments and data analysis. \u003cstrong\u003eDV\u003c/strong\u003e and \u003cstrong\u003eYR\u003c/strong\u003e were responsible for designing the \u003cem\u003ein vitro\u003c/em\u003e study. \u003cstrong\u003eRS\u003c/strong\u003e, \u003cstrong\u003eYV\u003c/strong\u003e, and \u003cstrong\u003eSR\u003c/strong\u003e participated in conducting the \u003cem\u003ein vitro\u003c/em\u003e experiments, and \u003cstrong\u003eSS\u003c/strong\u003e provided in vitro and funding support. All listed authors have reviewed and approved this study for publication.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence to\u0026nbsp;V.R.S.Kumar: [email protected] / [email protected]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods:\u003c/strong\u003e \u003cstrong\u003eIn vitro\u0026nbsp;\u003c/strong\u003emethod.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement:\u003c/strong\u003e The data that support the findings of this study are available within the article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors report no conflicts of interest relevant to this manuscript, with the exception of pending related patent applications in India.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e\u0026nbsp; Approved by Institutional Ethics Committee of Amity Institute of Aerospace Engineering, Amity University Uttar Pradesh (Approval No. DST-Amity-TEC-AIAE/VRS/P1_477/2025)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent statement:\u003c/strong\u003e\u0026nbsp; Written informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDepartment of Science and Technology (DST), Government of India \u0026nbsp;(Amity University Technology Enabling Centre - \u003cstrong\u003eProject Code:\u003c/strong\u003e AUUP/2019/477), \u0026nbsp; DST-Amity-TEC project No. AUUP/AIAE/VRS/ P1/2023–2025).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSanal Kumar VR, Radhakrishnan PK, Panchal D, et al. In vitro evidence of bubble-induced acoustic softening and Sanal flow choking in cardiovascular decompression. \u003cem\u003enpj Microgravity\u003c/em\u003e. 2025;11(54). doi:10.1038/s41526-025-00517-5\u003c/li\u003e\n \u003cli\u003eSanal Kumar VR, Radhakrishnan PK, Panchal D, et al. Microbubble-Induced Shock Waves in Blood: Investigating Multiphase Sanal Flow Choking During Decompression. \u003cem\u003eCirc Res\u003c/em\u003e. 2025;137(Suppl_1):Fri015. https://www.ahajournals.org/doi/abs/10.1161/res.137.suppl_1.Fri015\u003c/li\u003e\n \u003cli\u003eSanal Kumar VR, Choudhary SK, Radhakrishnan PK, Anbu J, Deveswaran R, Bharath S, et al. Elevated blood vapor pressure and reduced heat capacity of blood lead to gas embolism causing flow choking in gravity and microgravity environments. \u003cem\u003eNASA Human Research Program Investigators\u0026rsquo; Workshop\u003c/em\u003e; February 13\u0026ndash;16, 2024. Abstract No. 1646500.\u003c/li\u003e\n \u003cli\u003eSanal Kumar VR, Radhakrishnan PK. Sanal flow choking in cardiovascular systems is not a scientific fallacy but a groundbreaking concept. \u003cem\u003eIndian J Thorac Cardiovasc Surg\u003c/em\u003e. 2024. doi:10.1007/s12055-024-01859-7\u003c/li\u003e\n \u003cli\u003eSanal Kumar VR, Panchal D, Sharma R, Vohra YN, Rana S, Dekkala V, Raj Y, Singh S, Radhakrishnan PK. Decompression-induced microbubble choking in blood: acoustic softening, Sanal flow choking, and spaceflight implications. \u003cem\u003eAIAA SciTech 2026 Forum\u003c/em\u003e. AIAA Paper No. 2026-0720. Published on January 8, 2026. doi:10.2514/6.2026-0720.\u003c/li\u003e\n \u003cli\u003eAnbu J, Deveswaran R, Bharath S, et al. Animal in vivo proof of flow choking and bulging of stenotic arteries due to air embolism. \u003cem\u003eCirc Res\u003c/em\u003e. 2022;131(Suppl_1):P3028.\u003c/li\u003e\n \u003cli\u003ePanchal D, Singh S, Kumar R, Sanal Kumar VR. Microbubble dynamics in hydrocarbon fuels under reduced pressure: Experimental insights into acoustic softening and Sanal flow choking. \u003cem\u003eAppl Therm Eng\u003c/em\u003e. 2025;280(Pt 5):128471. doi:10.1016/j.applthermaleng.2025.128471\u003c/li\u003e\n \u003cli\u003eSanal Kumar VR. Sanal flow choking leads to hemorrhagic stroke and other neurological disorders in Earth and spaceflight. \u003cem\u003eCirc Res\u003c/em\u003e. 2021;129(Suppl_1):P422.\u003c/li\u003e\n \u003cli\u003eSanal Kumar VR. Lopsided blood-thinning drug increases risk of internal flow choking and shock wave generation causing asymptomatic stroke. \u003cem\u003eStroke\u003c/em\u003e. 2021;52(Suppl_1):P804.\u003c/li\u003e\n \u003cli\u003eSanal Kumar VR, Sankar V, Chandrasekaran N, et al. Boundary layer blockage, Venturi effect and cavitation causing aerodynamic choking and shock waves in human artery leading to massive heart attack. \u003cem\u003eAIAA Paper\u003c/em\u003e. 2018;No. 2018-3962.\u003c/li\u003e\n \u003cli\u003eHerrick JB. Clinical features of sudden obstruction of the coronary arteries. \u003cem\u003eJAMA\u003c/em\u003e. 1912;59(23):2015-2022. doi:10.1001/jama.1912.04270120001001\u003c/li\u003e\n \u003cli\u003eAtchley AA, Prosperetti A. The crevice model of bubble nucleation. \u003cem\u003eJ Acoust Soc Am\u003c/em\u003e. 1989;86:1065-1074. doi:10.1121/1.398343\u003c/li\u003e\n \u003cli\u003eLeighton TG. \u003cem\u003eThe Acoustic Bubble\u003c/em\u003e. Academic Press; 1994.\u003c/li\u003e\n \u003cli\u003eSanal Kumar, V. R., Choudhary SK, Radhakrishnan PK, et al., Nanoscale Flow Choking and Spaceflight Effects on Cardiovascular Risk of Astronauts \u0026ndash; A New Perspective. \u003cem\u003eAIAA SciTech Forum\u003c/em\u003e; 2021. Paper No. AIAA 2021-0357. Published online January 4, 2021. doi:10.2514/6.2021-0357.\u003c/li\u003e\n \u003cli\u003eSanal Kumar, V. R. et al. \u003cem\u003eBoundary Layer Blockage, Venturi Effect and Cavitation Causing Aerodynamic Choking and Shock Waves in Human Artery Leading to Hemorrhage and Massive Heart Attack\u0026mdash;a New Perspective\u003c/em\u003e AIAA Paper No 3962. 2018. https://doi.org/10.2514/6.2018-3962 (2018).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Sudden cardiac arrest, Microbubble nucleation, Acoustic softening, Sanal flow choking, Vapor lock, Shock-wave endothelial injury","lastPublishedDoi":"10.21203/rs.3.rs-9254931/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9254931/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Sudden cardiac arrest (SCA) in individuals without structural or electrical abnormalities remains an unresolved clinical problem. Here we report a pilot translational study investigating whether pressure-driven microbubble dynamics in human blood can generate physical conditions capable of destabilizing cardiovascular flow. Venous blood from healthy adult volunteers (n = 10) was subjected to controlled decompression (760→100 mmHg) at physiological temperature (37–40 °C), while high-speed imaging quantified microbubble nucleation, growth, coalescence and rupture. Microbubble formation consistently initiated below ~600 mmHg, followed by coalescence into transient gas cavities resembling vapor-lock structures. Increasing void fraction was associated with pronounced acoustic softening, with modeled effective sound speed decreasing from ~1500 m s⁻¹ to \u003c100 m s⁻¹. Surface roughness significantly increased nucleation density (p \u003c 0.05). Bubble rupture events produced localized transient pressure disturbances. Although bulk flow was not imposed, the observed acoustic-softening regime defines mechanical conditions permissive for multiphase flow choking in dynamic systems. These findings establish mechanistic feasibility for a physics-based cascade linking decompression-induced microbubble dynamics, acoustic softening and potential flow instability, motivating future in vivo and dynamic investigations into unexplained sudden cardiac collapse.","manuscriptTitle":"Acoustic Softening in Human Blood Induced by Microbubble Dynamics Under Decompression: Implications for Sudden Cardiac Collapse","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-01 07:01:44","doi":"10.21203/rs.3.rs-9254931/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"96c0a0fa-4739-4d84-a396-d4a30d49086b","owner":[],"postedDate":"April 1st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":65386369,"name":"Physical sciences/Engineering/Biomedical engineering"},{"id":65386370,"name":"Biological sciences/Physiology/Cardiovascular biology/Cardiovascular diseases/Heart failure"},{"id":65386371,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2026-04-01T07:01:51+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-01 07:01:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9254931","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9254931","identity":"rs-9254931","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}