Freigang K D, Bauer A, Becker R, Senges J C, Kraft P, Brachmann J, Kübler W, Schoels W
Department of Cardiology, University of Heidelberg, Germany.
Cardiovasc Res. 1997 Jul;35(1):52-9. doi: 10.1016/s0008-6363(97)00095-3.
The aim of the study was to investigate the differential effects of the class III agent, d-sotalol, on conduction and refractoriness on normal and infarcted areas of the canine ventricle.
Epicardial mapping studies were performed in 6 dogs 5-7 days after ligation of the left descending coronary artery using a specially designed patch electrode which contained 192 bipolar electrodes. Normal and infarcted areas were differentiated with respect to their macroscopic appearance and electrophysiological properties. Activation maps and local effective refractory periods (ERP) were determined before and after the administration of d-sotalol (1.5 mg/kg) at cycle lengths of 250, 300 and 350 ms.
Conduction and refractoriness were relatively homogeneous in the normal zone (NZ), contrasting with inhomogeneity in the infarct zone (IZ). In 2 dogs d-sotalol produced regional delay and block of conduction, exclusively in the IZ. The relative increase in refractoriness (delta ERP) after d-sotalol was significantly more pronounced in the IZ than in vs the NZ. In the NZ, delta ERP was most prominent at the longest (350 ms) and least prominent at the shortest (250 ms) basic pacing cycle lengths (11.5 +/- 2.8 vs. 7.3 +/- 1.4%; P < 0.05). The effect of d-sotalol in the IZ was independent of the basic pacing cycle length.
d-Sotalol preferentially prolonged refractoriness in the IZ of the canine ventricle. This effect and the lack of rate-dependence in the IZ could provide a possible explanation for both the potent antiarrhythmic and potential antiarrhythmic effect of d-sotalol.
本研究旨在探讨Ⅲ类药物d - 索他洛尔对犬心室正常区域和梗死区域的传导及不应期的不同影响。
在6只犬结扎左冠状动脉前降支5 - 7天后,使用包含192个双极电极的特制贴片电极进行心外膜标测研究。根据正常区域和梗死区域的宏观外观及电生理特性进行区分。在周期长度为250、300和350毫秒时,于给予d - 索他洛尔(1.5毫克/千克)前后测定激动标测图和局部有效不应期(ERP)。
正常区域(NZ)的传导和不应期相对均匀,与梗死区域(IZ)的不均匀性形成对比。在2只犬中,d - 索他洛尔仅在梗死区域导致区域性传导延迟和阻滞。d - 索他洛尔给药后,梗死区域的不应期相对增加(ΔERP)比正常区域明显更显著。在正常区域,ΔERP在最长(350毫秒)基本起搏周期长度时最为显著,在最短(250毫秒)时最不显著(11.5±2.8%对7.3±1.4%;P < 0.05)。d - 索他洛尔在梗死区域的作用与基本起搏周期长度无关。
d - 索他洛尔优先延长犬心室梗死区域的不应期。这种效应以及梗死区域缺乏频率依赖性可能为d - 索他洛尔强大的抗心律失常作用和潜在的致心律失常作用提供一种可能的解释。