Female hormones prevent sepsis-induced cardiac dysfunction: an experimental randomized study

Introduction: Although epidemiologic research has demonstrated significant differences in incidence and outcomes of sepsis according to gender, their underlying biological mechanisms are poorly understood. Here, we studied the influence of hormonal status by comparing in vivo cardiac performances measured by MRI in non-ovariectomized and ovariectomized septic female rats. Methods: : Control and ovariectomized rats were randomly allocated to the following groups: sham, sepsis and sepsis plus landiolol. Sepsis was induced by caecum ligation and punction (CLP). Cardiac MRI was carried out 18 hours after induction of sepsis to assess in vivo cardiac function. Capillary permeability was evaluated by Evans Blue administration and measurement of its tissue extravasation. Variation in myocardial gene expression was also assessed by qPCR in the left ventricular tissue. Results: Sepsis reduced indexed stroke volume, cardiac index and indexed end-diastolic volume compared to sham group in ovariectomized females whereas it had no effect in control females. Landiolol increased the indexed stroke volume by reversing the indexed end-diastolic volume reduction after sepsis in ovariectomized females, while it decreased indexed stroke volume and cardiac index in control. Major differences in the left ventricular expression of genes coding for calcium signalling and contractile proteins were observed in ovariectomized females compared to control after sepsis, partially restored by landiolol. Moreover, in control females, increase of apoptotic genes by sepsis was maintained after landiolol infusion. Conclusions: : Sepsis decreased in vivo cardiac performances in ovariectomized females but not in control females, presumably associated with apoptosis and calcium protein-related contractility defects. Administration of landiolol prevents this cardiac dysfunction in ovariectomized females, while it has deleterious effects in control females.