Bril A, Rochette L, Verry A, Maupoil V, Man R Y, Opie L H
Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Canada.
Cardiovasc Res. 1990 Aug;24(8):669-75. doi: 10.1093/cvr/24.8.669.
The aim was to evaluate the arrhythmogenic effect of a free radical generating system, FeCl3/ADP using two different approaches.
Ventricular arrhythmias were studied in isolated rat hearts subjected to regional ischaemia and reperfusion without or with simultaneous treatment with nicergoline (0.4 mg.litre-1). In the second part of this study the electrophysiological effects of FeCl3/ADP (0.1/1.0 microM) were investigated in normal Purkinje fibres and in Purkinje fibres from dog surviving infarction, by using conventional microelectrode method.
Hearts were obtained from male Sprague-Dawley rats, weight 250-300 g. Purkinje fibres were dissected from hearts of mongrel dogs of either sex (10-15 kg) with or without prior myocardial infarction.
FeCl3/ADP (0.1/1.0 microM and 1.0/1.0 microM respectively) weakly changed the incidence of reperfusion induced arrhythmias. In nicergoline pretreated hearts, in which the incidence of reperfusion arrhythmias was reduced, FeCl3/ADP (0.1/1.0 microM and 1.0/1.0 microM) did not change the incidence and the duration of reperfusion arrhythmias. In normal Purkinje fibres, FeCl3/ADP (0.1/1.0 microM) induced a decrease in action potential duration without any pronounced effect on Vmax, diastolic potential, and activation potential. In Purkinje fibres from post infarct myocardium, FeCl3/ADP decreased action potential duration, diastolic potential, and activation potential.
Free radical generation did not antagonise the antiarrhythmic activity of alpha adrenergic blockade. Free radical generation induced slow and minor changes in electrophysiological activity of Purkinje fibres both from normal and ischaemic hearts. Our data suggest that free radical generation may not be the only mechanism involved in the genesis of reperfusion arrhythmias.
旨在使用两种不同方法评估自由基生成系统FeCl3/ADP的致心律失常作用。
在离体大鼠心脏中研究局部缺血和再灌注时的室性心律失常,这些心脏未接受或同时接受了尼麦角林(0.4毫克/升)治疗。在本研究的第二部分,通过传统微电极方法研究了FeCl3/ADP(0.1/1.0微摩尔)对正常浦肯野纤维和梗死存活犬的浦肯野纤维的电生理作用。
心脏取自体重250 - 300克的雄性Sprague-Dawley大鼠。浦肯野纤维从雄性或雌性杂种犬(10 - 15千克)的心脏中分离,这些犬有无心肌梗死。
FeCl3/ADP(分别为0.1/1.0微摩尔和1.0/1.0微摩尔)对再灌注诱导的心律失常发生率影响微弱。在尼麦角林预处理的心脏中,再灌注心律失常发生率降低,FeCl3/ADP(0.1/1.0微摩尔和1.0/1.0微摩尔)未改变再灌注心律失常的发生率和持续时间。在正常浦肯野纤维中,FeCl3/ADP(0.1/1.0微摩尔)使动作电位时程缩短,而对最大去极化速率、舒张电位和阈电位无明显影响。在梗死心肌后的浦肯野纤维中,FeCl3/ADP使动作电位时程、舒张电位和阈电位降低。
自由基生成未拮抗α肾上腺素能阻断的抗心律失常活性。自由基生成在正常和缺血心脏的浦肯野纤维电生理活性中引起缓慢且微小的变化。我们的数据表明,自由基生成可能不是再灌注心律失常发生的唯一机制。