Susceptibility to ischemia-induced ventricular fibrillation in isolated female rat hearts varies moderately with estrous cycle stage

Abstract

IntroductionThe vast majority of studies employing the isolated perfused rat heart model to study ischemic arrhythmias have used male rats only. The objective of this study was to determine the susceptibility to ischemia-induced ventricular fibrillation (VF) in isolated female rat hearts in each stage of the estrous cycle that corresponds with a different endogenous reproductive hormonal environment. MethodsHearts were isolated from female rats under pentobarbital anesthesia and perfused with modified Krebs solution containing 3mM K+. Experiments were grouped according to estrous cycle stage that was determined by prior vaginal lavage (n=10–13 per group). A group of male rat hearts was used as the control. Regional ischemia was induced by coronary ligation and maintained for 30min. The incidence of VF was determined from the ECG. ResultsThe incidence of VF in male hearts was 100%, while the incidence of VF in female hearts was also high but varied moderately with stage of the estrous cycle (diestrus 70%, metestrus 100%, proestrus 90%, estrus 69%; P>0.05). Compared to male hearts, the onset of VF was similar in all groups except for hearts excised from rats in proestrus, in which it was delayed. There was no difference between groups in an arrhythmia score, ischemic zone size, or baseline electrocardiographic or hemodynamic variables. DiscussionIn conclusion, the susceptibility of isolated female rat hearts to ischemic VF is comparable to that of male rat hearts, meaning that isolated female rat hearts can be used as controls in studies to assess antiarrhythmic drug efficacy. Since female rats can be used for isolated heart studies of ischemic VF, the need to cull female rats is reduced. However, the variation in VF susceptibility in female rat hearts that is associated with the different stages of the estrous cycle may affect statistical power that could potentially lead to Type II statistical errors. This problem can be prevented with careful randomization.