Scholz W, Albus U, Linz W, Martorana P, Lang H J, Schölkens B A
Hoechst AG, Frankfurt/M., Germany.
J Mol Cell Cardiol. 1992 Jul;24(7):731-9. doi: 10.1016/0022-2828(92)93387-y.
To investigate a possible protective role of Na+/H+ exchange inhibition under ischemic conditions isolated rat hearts were subjected to regional ischemia and reperfusion. In these experiments all 6 untreated hearts suffered ventricular fibrillation on reperfusion. Addition of 1 x 10(-5) mol/l amiloride or 3 x 10(-7) mol/l 5-(N-ethyl-N-isopropyl)amiloride (EIPA) markedly decreased the incidence and duration of ventricular fibrillation or even suppressed fibrillation completely as in the case of 1 x 10(-6) mol/l EIPA. Both compounds diminished the activities of lactate dehydrogenase and creatine kinase in the venous effluent of the hearts during ischemia. At the end of the experiments tissue contents of glycogen, ATP and creatine phosphate were increased in the treated hearts as compared to control hearts. In an additional experiment the beneficial effects of Na+/H+ exchange inhibition during ischemia was confirmed in vivo with anaesthetized rats undergoing coronary artery ligation. In these animals amiloride or EIPA pretreatment caused a marked reduction of ventricular premature beats and ventricular tachycardia as well as a complete suppression of ventricular fibrillation. The concentration dependent inhibition of Na+ influx via Na+/H+ exchange by amiloride and EIPA was investigated in erythrocytes from hypercholesterolemic rabbits with Na+/H+ exchange activated by exposure to hyperosmotic medium. Furthermore the inhibition of Na+ influx by EIPA after intracellular acidification was studied in cardiac myocytes of neonatal rats. Both agents were effective in the same order of potency in the ischemic isolated working rat heart as in the erythrocyte model in which they inhibited Na+/H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)
为了研究在缺血条件下抑制Na⁺/H⁺交换可能具有的保护作用，对离体大鼠心脏进行了局部缺血和再灌注实验。在这些实验中，所有6颗未处理的心脏在再灌注时均发生心室颤动。添加1×10⁻⁵mol/L的氨氯吡脒或3×10⁻⁷mol/L的5-(N-乙基-N-异丙基)氨氯吡脒（EIPA）可显著降低心室颤动的发生率和持续时间，甚至如1×10⁻⁶mol/L EIPA的情况那样完全抑制颤动。两种化合物均可降低缺血期间心脏静脉流出液中乳酸脱氢酶和肌酸激酶的活性。实验结束时，与对照心脏相比，处理过的心脏中糖原、三磷酸腺苷（ATP）和磷酸肌酸的组织含量增加。在另一项实验中，对接受冠状动脉结扎的麻醉大鼠进行体内实验，证实了缺血期间抑制Na⁺/H⁺交换的有益作用。在这些动物中，氨氯吡脒或EIPA预处理可显著减少室性早搏和室性心动过速，并完全抑制心室颤动。在高胆固醇血症兔的红细胞中，研究了氨氯吡脒和EIPA对通过Na⁺/H⁺交换的Na⁺内流的浓度依赖性抑制作用，这些红细胞通过暴露于高渗介质激活Na⁺/H⁺交换。此外，还在新生大鼠的心肌细胞中研究了细胞内酸化后EIPA对Na⁺内流的抑制作用。在缺血的离体工作大鼠心脏中，这两种药物的效力顺序与它们在抑制Na⁺/H⁺交换的红细胞模型中相同。（摘要截短于250字）
