Grover G J, Dzwonczyk S, Sleph P G
Department of Pharmacology, Squibb Institute for Medical Research, Princeton, N.J.
Pharmacology. 1990;40(3):137-49. doi: 10.1159/000138652.
A comparison was made of the anti-ischemic effects of dihydropyridine calcium antagonists in isolated globally ischemic rat hearts. Pretreatment with amlodipine, nifedipine, nitredipine, or nisoldipine reduced reperfusion enzyme (lactate dehydrogenase) release and contracture after 25 min of global ischemia and 30 min of reperfusion. Increasing concentrations of all compounds resulted in proportionally smaller reductions in the severity of ischemia, with larger decreases in nonischemic tissue contractility occurring. Reperfusion function was significantly improved at 30 min with nifedipine only; however, at 60 min reperfusion function was significantly improved for all except nisoldipine. Washout data from nonischemic hearts (rate of disappearance of cardiodepressant effects) showed that the dihydropyridines washed out in the following order (fastest to slowest): nifedipine greater than nitrendipine greater than nisoldipine greater than amlodipine. Thus, these dihydropyridines are anti-ischemic, though at higher concentrations cardiodepressant effects increase disproportionately. Differences in washout also effect the ability of these compounds to improve reperfusion function.
对二氢吡啶类钙拮抗剂在离体全心缺血大鼠心脏中的抗缺血作用进行了比较。用氨氯地平、硝苯地平、尼群地平或尼索地平预处理可减少25分钟全心缺血和30分钟再灌注后的再灌注酶（乳酸脱氢酶）释放及挛缩。所有化合物浓度增加时，缺血严重程度的降低幅度相应减小，同时非缺血组织收缩性的降低幅度增大。仅硝苯地平在30分钟时可显著改善再灌注功能；然而，在60分钟时，除尼索地平外，其他药物均可显著改善再灌注功能。非缺血心脏的洗脱数据（心脏抑制作用消失速率）表明，二氢吡啶类药物的洗脱顺序如下（从最快到最慢）：硝苯地平＞尼群地平＞尼索地平＞氨氯地平。因此，这些二氢吡啶类药物具有抗缺血作用，尽管在较高浓度下心脏抑制作用会不成比例地增加。洗脱差异也会影响这些化合物改善再灌注功能的能力。
