Khatter J C, Navaratnam S, Hoeschen R J
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Pharmacology. 1988;36(6):380-9. doi: 10.1159/000138326.
Protective influence of verapamil upon ouabain-induced cardiac arrhythmias was investigated in anesthetized (alpha-chloralose 60 mg/kg and urethane 500 mg/kg) open-chest guinea pigs. Verapamil in doses between 100 and 150 micrograms/kg significantly increased (80-90%) the dose of ouabain, necessary to cause ventricular arrhythmias. This was also associated with a larger survival rate. A larger dose of verapamil (225 micrograms/kg) caused a further increase in the dose of ouabain, necessary for the initiation of arrhythmias, but in all the cases second or third degree heart block occurred. Verapamil (150 micrograms/kg) also prevented the development of fatal arrhythmias and death, when it was administered at the onset of ventricular ectopy. However, once the arrhythmias were firmly established, verapamil was ineffective in reversing the toxic response. The data suggests that verapamil exerts a protective effect against the development of digitalis-induced cardiac arrhythmias in doses which are comparable to therapeutic levels in humans. The larger doses of verapamil, however, will be contradicted because of the slowing of AV node and the likelihood of complete heart block.
在麻醉（α-氯醛糖60mg/kg和乌拉坦500mg/kg）的开胸豚鼠中研究了维拉帕米对哇巴因诱发的心律失常的保护作用。剂量在100至150微克/千克之间的维拉帕米显著增加（80-90%）了诱发室性心律失常所需的哇巴因剂量。这也与更高的存活率相关。更大剂量的维拉帕米（225微克/千克）使诱发心律失常所需的哇巴因剂量进一步增加，但在所有情况下均出现了二度或三度心脏传导阻滞。当在室性早搏发作时给予维拉帕米（150微克/千克），它也能预防致命性心律失常的发生和死亡。然而，一旦心律失常牢固确立，维拉帕米在逆转毒性反应方面无效。数据表明，维拉帕米在与人类治疗水平相当的剂量下，对洋地黄诱发的心律失常的发生具有保护作用。然而，更大剂量的维拉帕米会因房室结减慢和完全性心脏传导阻滞的可能性而产生矛盾。
