Auchampach J A, Gross G J
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Eur Heart J. 1993 Jul;14 Suppl B:10-5. doi: 10.1093/eurheartj/14.suppl_b.10.
The effect of three potassium channel openers, nicorandil, aprikalim, and bimakalim, on experimental myocardial ischaemia/reperfusion injury was examined in barbital-anaesthetized dogs. In a model of reversible injury, administration of nicorandil at a hypotensive dose and aprikalim at a non-hypotensive dose resulted in a reduction in contractile dysfunction during reperfusion ('stunning') following brief coronary artery occlusion (15 min) when the drugs were administered before occlusion. Administration of aprikalim only during reperfusion had no beneficial effect. Pre-treatment with the adenosine triphosphate (ATP)-dependent potassium (KATP) channel antagonist, glibenclamide, blocked completely the beneficial effects of nicorandil and aprikalim, although glibenclamide did not block the haemodynamic effects of nicorandil. In a model of irreversible ischaemia/reperfusion injury (120 min of ischaemia and 30 min of reperfusion) pre-treatment with equihypotensive doses of nicorandil and bimakalim produced marked reductions in myocardial infarct size. Similarly, aprikalim at a non-hypotensive dose reduced myocardial infarct size in dogs subjected to 90 min of ischaemia and 5 h of reperfusion, and the protective effects of aprikalim were antagonized completely by glibenclamide. These results indicate that nicorandil, aprikalim, and bimakalim are protective in two experimental models of ischaemia/reperfusion injury. The mechanism of action of these agents is not completely understood, but it appears to be a result of myocardial KATP channel activation.
在巴比妥麻醉的犬中研究了三种钾通道开放剂尼可地尔、阿普卡林和比马卡林对实验性心肌缺血/再灌注损伤的影响。在可逆性损伤模型中，当在冠状动脉闭塞（15分钟）前给药时，给予降压剂量的尼可地尔和非降压剂量的阿普卡林可减少再灌注期间（“顿抑”）的收缩功能障碍。仅在再灌注期间给予阿普卡林没有有益作用。用三磷酸腺苷（ATP）依赖性钾（KATP）通道拮抗剂格列本脲预处理可完全阻断尼可地尔和阿普卡林的有益作用，尽管格列本脲不阻断尼可地尔的血流动力学作用。在不可逆性缺血/再灌注损伤模型（缺血120分钟和再灌注30分钟）中，用等降压剂量的尼可地尔和比马卡林预处理可显著减小心肌梗死面积。同样，非降压剂量的阿普卡林可减小缺血90分钟和再灌注5小时犬的心肌梗死面积，且阿普卡林的保护作用被格列本脲完全拮抗。这些结果表明，尼可地尔、阿普卡林和比马卡林在两种缺血/再灌注损伤实验模型中具有保护作用。这些药物的作用机制尚未完全阐明，但似乎是心肌KATP通道激活的结果。
