Li G R, Ferrier G R
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
J Cardiovasc Pharmacol. 1991 Feb;17(2):239-48. doi: 10.1097/00005344-199102000-00009.
Transmembrane electrical activity from endo- and epicardium and a high-gain ECG were recorded from isolated segments of guinea pig right ventricles. Endocardium was stimulated. Tissues were exposed to ischemic conditions for 15 min and then reperfused with "normal" Tyrode's solution. Ventricular tachycardia, bigeminy, or trigeminy with characteristics of transmural reentry occurred in early reperfusion in 68% of control hearts. Arrhythmias were associated with prolongation of the transmural conduction time (CT) and abbreviation of the endocardial effective refractory period (EP). Quinidine significantly suppressed reperfusion arrhythmias at 1 and 5 microM, slightly increased the incidence of arrhythmias at 10 microM, and again suppressed arrhythmias at 50 and 100 microM. At 1 and 5 microM, quinidine prevented or attenuated prolongation of the transmural CT by ischemic conditions and reperfusion. The transmural CT was not significantly changed at 10 microM, and was further prolonged at 50 and 100 microM quinidine. The endocardial ERP was prolonged by 50 and 100 microM quinidine during ischemic conditions and reperfusion. In epicardial slices, 5 microM quinidine shortened the CT transverse to the fiber orientation during reperfusion but had no effect on the longitudinal CT. Thus, antiarrhythmic efficacy of low concentrations of quinidine may occur through differential effects dependent on tissue anisotropy.
从豚鼠右心室分离段记录心内膜和心外膜的跨膜电活动以及高增益心电图。刺激心内膜。组织暴露于缺血状态15分钟，然后用“正常”台氏液再灌注。68%的对照心脏在再灌注早期出现具有跨壁折返特征的室性心动过速、二联律或三联律。心律失常与跨壁传导时间（CT）延长和心内膜有效不应期（EP）缩短有关。奎尼丁在1和5微摩尔浓度时显著抑制再灌注心律失常，在10微摩尔浓度时轻微增加心律失常发生率，在50和100微摩尔浓度时又抑制心律失常。在1和5微摩尔浓度时，奎尼丁可预防或减轻缺血状态和再灌注导致的跨壁CT延长。在10微摩尔浓度时跨壁CT无显著变化，在50和100微摩尔浓度的奎尼丁作用下跨壁CT进一步延长。在缺血状态和再灌注期间，50和100微摩尔浓度的奎尼丁可延长心内膜ERP。在心外膜切片中，5微摩尔浓度的奎尼丁在再灌注期间缩短了与纤维方向垂直的CT，但对纵向CT无影响。因此，低浓度奎尼丁的抗心律失常作用可能通过依赖于组织各向异性的差异效应而产生。
