The effect of sex and age on ex vivo cardiac electrophysiology: insight from a guinea pig model

Abstract

Highlighting the importance of sex as a biological variable, we recently reported sex differences in guinea pig in vivo electrocardiogram (ECG) measurements. However, substantial inconsistencies exist in this animal model - with conflicting reports of sex-specific differences in cardiac electrophysiology observed in vivo versus in vitro. Herein, we evaluated whether sexual dimorphism persists between in vivo and ex vivo preparations, using an isolated intact heart preparation. Pseudo-ECG recordings were collected in conjunction with dual optical mapping of transmembrane voltage and intracellular calcium from Langendorff-perfused hearts. In contrast to our in vivo results, we did not observe sex-specific differences in ECG parameters collected from isolated hearts. Further, we observed significant age-specific differences in action potential duration (APD) and Ca2+ transient duration (CaD) during both normal sinus rhythm (NSR) and in response to dynamic pacing; but, only a modest sex-specific difference in CaD30. Similarly, the alternans fluctuation coefficient, conduction velocity during sinus rhythm or in response to pacing, and electrophysiology parameters (atrioventricular nodal effective refractory period, Wenckebach cycle length) were comparable between males and females. Results of our study suggest that the observed sex-specific differences in in vivo ECG parameters from guinea pigs are largely negated in ex vivo isolated heart preparations; although, age-specific patterns are prevalent. To assess sex as a biological variable in cardiac electrophysiology, a comprehensive approach may be necessary using both in vitro measurements from cardiomyocyte or intact heart preparations with secondary follow-up in vivo studies.

Electroanatomical Adaptations in the Guinea Pig Heart from Neonatal to Adulthood

“…Both human 5,34 and guinea pig 24,25 studies have reported an age-dependent effect on ECG parameters. Although, to date, preclinical studies have largely been limited to adults – with no comparison between pediatric and adult guinea pigs.…”

“…ECG recordings were performed as previously described 24,25 . Briefly, animals were anesthetized with 2–3% isoflurane for 10 minutes.…”

“…Intact heart isolation was performed as described previously 25 . Briefly, guinea pigs were anesthetized with 2–3% isoflurane until achieving a surgical depth, as determined by an ear pinch test.…”

Role of low-density lipoprotein electronegativity and sexual dimorphism in contributing early ventricular tachyarrhythmias following ST-elevation myocardial infarction

“…To unravel the mechanisms underpinning the higher susceptibility of males to early VT/VF following STEMI, we employed a pertinent ApoE −/− mouse model subjected to ex vivo ischemia-reperfusion, mimicking the reperfusion injury experienced by STEMI patients undergoing primary percutaneous coronary intervention therapy ( 30 ). Our findings revealed a greater predisposition towards VT and VF in male ApoE −/− mice post-ischemia-reperfusion injury, aligning with the observed male dominance in clinical scenarios involving STEMI patients receiving reperfusion therapy.…”

KairoSight-3.0: A validated optical mapping software to characterize cardiac electrophysiology, excitation-contraction coupling, and alternans

“…Animals were anesthetized with 2–3 % isoflurane, until a surgical depth of anesthesia was reached as determined by a tail pinch test (rats) or ear pinch test (guinea pigs) [ 17 , 18 ]. Animals were euthanized by exsanguination following heart excision.…”