Hoque A N, Hoque N, Hashizume H, Abiko Y
Department of Pharmacology, Asahikawa Medical College, Japan.
Jpn J Pharmacol. 1995 Mar;67(3):225-32. doi: 10.1254/jjp.67.225.
In the isolated, perfused working rat heart, ischemia (15 min) decreased the mechanical function and the tissue levels of adenosine triphosphate and creatine phosphate and increased the levels of lactate and free fatty acids. Reperfusion (20 min) did not restore the mechanical function, but restored incompletely the levels of metabolites, with the exception of free fatty acids, which increased further during reperfusion. Dilazep was given 5 min before starting ischemia until the end of ischemia. Dilazep at 5 or 10 microM decreased the cardiac mechanical function, but did not affect coronary flow in the pre-ischemic heart. Dilazep at 5 or 10 microM accelerated the recovery of mechanical function and coronary flow during reperfusion, and it attenuated metabolic changes induced by ischemia and reperfusion. Dilazep at 1 microM neither decreased the pre-ischemic mechanical function nor restored the mechanical function during reperfusion, although it attenuated the accumulation of free fatty acids during reperfusion. These results suggest that dilazep attenuates both ischemia- and reperfusion-induced myocardial damage and that the anti-ischemic action of dilazep is not due to coronary vasodilation but probably due to an energy-sparing effect and other effects that remain to be studied.
在离体灌注的工作大鼠心脏中，缺血（15分钟）会降低机械功能以及三磷酸腺苷和磷酸肌酸的组织水平，并增加乳酸和游离脂肪酸的水平。再灌注（20分钟）未能恢复机械功能，但除游离脂肪酸外，代谢物水平未完全恢复，游离脂肪酸在再灌注期间进一步增加。在开始缺血前5分钟给予地尔硫䓬直至缺血结束。5或10微摩尔的地尔硫䓬会降低心脏机械功能，但不影响缺血前心脏的冠脉血流。5或10微摩尔的地尔硫䓬可加速再灌注期间机械功能和冠脉血流的恢复，并减轻缺血和再灌注诱导的代谢变化。1微摩尔的地尔硫䓬既不会降低缺血前的机械功能，也不会在再灌注期间恢复机械功能，尽管它可减轻再灌注期间游离脂肪酸的蓄积。这些结果表明，地尔硫䓬可减轻缺血和再灌注诱导的心肌损伤，且地尔硫䓬的抗缺血作用并非由于冠脉血管舒张，可能是由于能量节省效应以及其他有待研究的效应。
