Mechanism of gender difference in sotalol-induced torsade de pointes / 中国病理生理杂志

ABSTRACT

AIM: To investigate the mechanism of gend er difference in sotalol-induced torsade de pointes (TdP) in rabbits in vitro. METHODS: 40 rabbits of both sexes were divided into two groups low concentration (1?10 -5 mol/L d-sotalol) group and high concentration (1?10 -4 mol/L d-sotalol) group. With the monophasic action potential (MAP ) recording technique, MAP of epicardium, midmyocardium and endocardium were sim ultaneously recorded by specially designed plunge-needle electrodes across the l eft ventricular free wall of rabbit hearts purfused by Langendorff method. TdP w as induced by bradycardia, d-sotalol and low-K+, Mg 2+ tyrode solution. RESULTS: d-sotalol prolonged the duration of 90% repolarizat ion (MAPD 90) of epicardium, midmyocardium and endocardium in a concentration-d ependent manner and the effect on midmyocardium was the most obvious. In low con centration group, MAPD 90 of midmyocardium of male rabbit heart increased f rom (222?11) ms to (230?10) ms and that of female rabbit heart increased from (263?12) ms to (281?12) ms. In high concentration group, MAPD 90 of midmy ocardium of male rabbit heart increased from (217?10) ms to (296?18) ms and th at of female rabbit heart increased from (258?10) ms to (368?19) ms. There was no difference in TDR between male and female rabbit hearts before perfusion wit h d-sotalol. D-sotalol prolonged TDR in a concentration-dependent manner. In low concentration group, TDR of male and female rabbit hearts was (20.0?5.1) ms and (28.0?5.6) ms. In high concentration group, TDR of male and female rabbit hearts was (38.0?4.8) ms and (55.0?7.7) ms, respectively. There was EAD i n 6 female hearts while no EAD develop ed in male heart and no TdP developed in low concentration group. In high concen tration group, 10 female, 9 male hearts developed EAD, 9 female and 3 male he arts developed TdP. CONCLUSION: The greater TDR induced by d-sotalol in female may b e responsible for the higher incidence of TdP of female rabbit heart.