Nakaya H
Hokkaido Igaku Zasshi. 1981 May;56(3):335-45.
Effects of Ca++-antagonists on the conduction delay observed in the ischemic myocardium were studied in open-chest anesthetized dogs. Complete occlusion of the left anterior descending coronary artery (LAD) for 5 or 10 min under a constant atrial pacing produced conduction delay in the ischemic zone. Lidocaine which was administered prior to the LD occlusion increased the conduction delay, whereas Ca++-antagonists, verapamil and diltiazem, reduced the ischemia-induced conduction delay. To determine whether the coronary vasodilating action of these Ca++-antagonists can play a role in reducing the ischemia-induced conduction delay by means of increasing the collateral blood flow, the effects of these Ca++-antagonists were compared with those of other coronary vasodilating drugs on the coronary circulation and the ischemia-induced conduction delay. Administration of verapamil, diltiazem, nifedipine, nitroglycerin+phenylephrine and dipyridamole increased both the blood flow of the left circumflex coronary artery and the regional myocardial blood flow at LAD area, whereas nitroglycerin alone decreased and isosorbide dinitrate hardly affected them. Nevertheless, only drugs possessing a slow channel blocking action, i.e. verapamil, diltiazem and a large dose of nifedipine, improved the conduction delay. Effects of verapamil on the conduction delay and potassium efflux induced by global myocardial ischemia were evaluated in isolated Langendorff-perfused rabbit hearts. Perfusion with a modified Tyrode solution containing 10-1000 ng/ml of verapamil prior to 7 min of global ischemia significantly prevented the intramyocardial conduction delay. However, the potassium efflux into the coronary effluents during ischemia and 1 min after reperfusion was not significantly reduced by verapamil. These results indicate that the favorable effect of Ca++-antagonists on the ischemia-induced conduction delay is not associated with the improvement of coronary circulation or the reduction of potassium efflux from the ischemic myocardium.
在开胸麻醉犬身上研究了钙离子拮抗剂对缺血心肌中观察到的传导延迟的影响。在持续心房起搏下，将左冠状动脉前降支（LAD）完全闭塞5或10分钟，可在缺血区产生传导延迟。在LAD闭塞前给予利多卡因会增加传导延迟，而钙离子拮抗剂维拉帕米和地尔硫䓬则可减少缺血诱导的传导延迟。为了确定这些钙离子拮抗剂的冠状动脉舒张作用是否可通过增加侧支血流来减少缺血诱导的传导延迟，将这些钙离子拮抗剂与其他冠状动脉舒张药物对冠状动脉循环和缺血诱导的传导延迟的影响进行了比较。给予维拉帕米、地尔硫䓬、硝苯地平、硝酸甘油+去氧肾上腺素和双嘧达莫可增加左旋冠状动脉的血流以及LAD区域的局部心肌血流，而单独给予硝酸甘油则使其减少，二硝酸异山梨酯几乎无影响。然而，只有具有慢通道阻滞作用的药物，即维拉帕米、地尔硫䓬和大剂量硝苯地平，可改善传导延迟。在离体Langendorff灌注兔心脏中评估了维拉帕米对全心缺血诱导的传导延迟和钾外流的影响。在全心缺血7分钟前，用含10 - 1000 ng/ml维拉帕米的改良台氏液灌注，可显著预防心肌内传导延迟。然而，维拉帕米并未显著减少缺血期间及再灌注后1分钟冠状动脉流出液中的钾外流。这些结果表明，钙离子拮抗剂对缺血诱导的传导延迟的有利作用与冠状动脉循环的改善或缺血心肌钾外流的减少无关。
