Testosterone does not shorten action potential duration in Langendorff-perfused rabbit ventricles

Background: Women have longer baseline QT intervals than men. Because previous studies showed that testosterone and 5α-dihydrotestosterone shorten the ventricular action potential duration (APD) in animal models, differential testosterone concentrations may account for the sex differences in QT interval. Objective: The purpose of this study was to test the hypothesis that testosterone shortens the APD in Langendorff-perfused rabbit ventricles. Methods: We performed optical mapping studies in hearts with or without testosterone administration. Acute studies included 26 hearts using 2 different protocols, including 17 without and 9 with atrioventricular (AV) block. For chronic studies, we implanted testosterone pellets subcutaneously in 7 female rabbits for 2–3 weeks before optical mapping studies during complete AV block. Six rabbits without pellet implantation served as controls. Results: The hearts in the acute studies were paced with a pacing cycle length (PCL) of 200–300 ms and mapped at baseline and after administration of 1 nM, 10 nM, 100 nM, and 3 μM of testosterone. There was no shortening of APD₈₀ at any PCL. Instead, a lengthening of APD₈₀ was noted at higher concentrations. There were no sex differences in testosterone responses. In chronic studies, heart rates were 136 ± 5 bpm before and 148 ± 9 bpm after (P = .10) while QTc intervals were 314 ± 9 ms before and 317 ± 99 ms after (P = .69) testosterone pellet implantation, respectively. Overall, ventricular APD₈₀ in the pellet group was longer than in the control group at 300- to 700-ms PCL. Conclusion: Testosterone does not shorten ventricular repolarization in rabbit hearts.