Karmazyn M, Ray M, Haist J V
Department of Pharmacology and Toxicology, University of Western Ontario, London, Canada.
J Cardiovasc Pharmacol. 1993 Jan;21(1):172-8. doi: 10.1097/00005344-199301000-00025.
To examine the role of Na+/H+ exchange in cardiac injury, we compared the effect of amiloride (174 microM) with the markedly more specific and potent inhibitor 5-(N,N-hexamethylene) amiloride (HMA, 1 microM) against cardiac injury produced by reperfusion, reoxygenation, and the calcium paradox. Reperfusion after 15-min ischemia resulted in a 55 +/- 4% recovery in contractility, whereas in the presence of amiloride or HMA, recovery was increased to 82 +/- 5.8 and 72 +/- 7.8%, respectively (p < 0.05 from control), with HMA showing particular efficacy in accelerating recovery. The rapid restoration of function with HMA was also evident in hearts reoxygenated for 1 min after 12-min hypoxia (control 35 +/- 3.2%, HMA 66 +/- 4.1%, p < 0.05) although the protective effect gradually reversed with continued reoxygenation. On the other hand, with addition of amiloride, the protective effect persisted so that after 30-min reoxygenation values were significantly higher than control (65 +/- 4.1 vs. 47 +/- 3.1%, p < 0.05). Resting tension increases after either reperfusion or reoxygenation were moderate: 124 +/- 8 and 119 +/- 6%, respectively (p > 0.05), but no increases were observed with amiloride or HMA. Bepridil (10 microM), a purported Na+/Ca2+ exchange inhibitor, exerted a salutary effect against reperfusion dysfunction identical to that of amiloride and HMA, whereas in reoxygenated hearts the effects were identical to those observed with HMA. The protective effects of the drugs were not related to improved energy metabolic status. None of the pharmacologic interventions exerted beneficial effects against the calcium paradox.(ABSTRACT TRUNCATED AT 250 WORDS)
为研究钠氢交换在心脏损伤中的作用，我们比较了氨氯吡脒（174微摩尔）与特异性更强、效力更高的抑制剂5-（N，N-六亚甲基）氨氯吡脒（HMA，1微摩尔）对再灌注、复氧及钙反常所导致的心脏损伤的影响。15分钟缺血后的再灌注使收缩性恢复了55±4%，而在氨氯吡脒或HMA存在的情况下，恢复率分别提高到了82±5.8%和72±7.8%（与对照组相比p<0.05），HMA在加速恢复方面显示出特别的效果。在12分钟缺氧后复氧1分钟的心脏中，HMA使功能快速恢复也很明显（对照组为35±3.2%，HMA为66±4.1%，p<0.05），尽管随着持续复氧，保护作用逐渐逆转。另一方面，加入氨氯吡脒后，保护作用持续存在，以至于复氧30分钟后的值显著高于对照组（65±4.1%对47±3.1%，p<0.05）。再灌注或复氧后静息张力的增加幅度适中：分别为124±8%和119±6%（p>0.05），但氨氯吡脒或HMA未观察到增加。苄普地尔（10微摩尔），一种据称的钠钙交换抑制剂，对再灌注功能障碍发挥了与氨氯吡脒和HMA相同的有益作用，而在复氧心脏中，其作用与HMA观察到的作用相同。药物的保护作用与改善能量代谢状态无关。没有一种药物干预措施对钙反常发挥有益作用。（摘要截短于250字）
