Haverkamp W, Thale J, Gülker H, Hindricks G, Bender F
University Hospital, Department of Cardiology and Angiology, Münster, FRG.
Eur Heart J. 1987 Aug;8 Suppl D:117-28. doi: 10.1093/eurheartj/8.suppl_d.117.
The effects of various calcium antagonists on ventricular arrhythmias, particularly fibrillation (VF), in relation to epicardial conduction delay during acute myocardial ischaemia and reperfusion were investigated in 40 open-chest anaesthetized dogs. Acute transient coronary artery occlusion lasting 20 min was performed in all animals. Sixteen dogs served as controls; diltiazem (D) (0.5 mg kg-1 iv), verapamil (V) (0.25 mg kg-1 iv), gallopamil (G) (0.13 mg kg-1 iv) and nifedipine (N) (0.04 mg kg-1 iv) were given in six animals each 5 min prior to coronary occlusion. Epicardial conduction delay was assessed by means of an epicardial mapping electrode array consisting of 42 bipolar electrodes. In the control group, conduction delay showed a bimodal time course in the ischaemic area with a maximum of 38 +/- 10 ms 6 min after coronary occlusion followed by partial improvement. After pretreatment with D, V or G the peak in conduction delay as well as the maximum dispersion of conduction times in the ischaemic area were significantly diminished, whereas N failed to improve conduction in the ischaemic area. Correspondingly, ventricular arrhythmias and VF were almost completely suppressed by D, V or G, but not affected by N. Following release of coronary artery occlusion none of the compounds proved to influence the rapid and heterogeneous improvement of conduction immediately after the onset of reperfusion. Correspondingly, none of the drugs diminished the incidence of VF immediately after release. Delayed ventricular reperfusion arrhythmias, arising parallel to complete restoration of conduction, were significantly reduced by D, V and G but not affected by N. Delayed and inhomogeneous activation of the ischaemic myocardium plays an important role in the genesis of ventricular arrhythmias in the early stage of acute myocardial ischaemia; thus a reduction in conduction delay and dispersion of conduction times seems to be a precondition for antiarrhythmic action. The different effects of calcium antagonists type V and type N on ischaemia-induced conduction delay and ventricular arrhythmias can be assumed to result from differences in the electropharmacological properties of the compounds.
在40只开胸麻醉犬中，研究了各种钙拮抗剂对急性心肌缺血和再灌注期间室性心律失常，尤其是心室颤动（VF）的影响，以及与心外膜传导延迟的关系。所有动物均进行了持续20分钟的急性短暂冠状动脉闭塞。16只犬作为对照；在冠状动脉闭塞前5分钟，分别给6只动物静脉注射地尔硫䓬（D）（0.5mg/kg）、维拉帕米（V）（0.25mg/kg）、加洛帕米（G）（0.13mg/kg）和硝苯地平（N）（0.04mg/kg）。通过由42个双极电极组成的心外膜标测电极阵列评估心外膜传导延迟。对照组中，缺血区域的传导延迟呈现双峰时间进程，冠状动脉闭塞后6分钟最大延迟为38±10毫秒，随后部分改善。用D、V或G预处理后，缺血区域传导延迟的峰值以及传导时间的最大离散度显著降低，而N未能改善缺血区域的传导。相应地，D、V或G几乎完全抑制了室性心律失常和VF，但N对其无影响。冠状动脉闭塞解除后，没有一种化合物被证明会影响再灌注开始后立即出现的传导快速且不均匀的改善。相应地，没有一种药物能降低解除闭塞后立即发生VF的发生率。与传导完全恢复平行出现的延迟性室性再灌注心律失常，D、V和G可使其显著减少，但N对其无影响。缺血心肌的延迟和不均匀激活在急性心肌缺血早期室性心律失常的发生中起重要作用；因此，传导延迟和传导时间离散度的降低似乎是抗心律失常作用的前提条件。V型和N型钙拮抗剂对缺血诱导的传导延迟和室性心律失常的不同作用可假定是由化合物的电药理特性差异所致。
