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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.

      Keywords

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      Linked Article

      • Sex differences in cardiac electrophysiology
        Heart RhythmVol. 19Issue 11
        • Preview
          Apart from a faster resting heart rate, the increased duration of the rate-corrected QTc interval likely is the most known and the most prominent physiological electrocardiographic difference between healthy adult females and males.1 In earlier reports, this sex difference was inflated by the use of the Bazett correction, which, combined with higher and lower heart rates, produces artificially prolonged and shortened QTc intervals, respectively. Nevertheless, the QTc sex difference is present even with more accurate, that is, subject-specific corrections.
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