Rupprecht H J, vom Dahl J, Terres W, Seyfarth K M, Richardt G, Schultheibeta H P, Buerke M, Sheehan F H, Drexler H
2nd Department of Internal Medicine, Johannes Gutenberg-University, Mainz, Germany.
Circulation. 2000 Jun 27;101(25):2902-8. doi: 10.1161/01.cir.101.25.2902.
Activation of Na(+)/H(+) exchange in myocardial ischemia and/or reperfusion leads to calcium overload and myocardial injury. Experimental studies have shown that Na(+)/H(+) exchange inhibitors can attenuate Ca(2+) influx into cardiomyocytes. We therefore performed a multicenter, randomized, placebo-controlled clinical trial to test the hypothesis that inhibition of Na(+)/H(+) exchange limits infarct size and improves myocardial function in patients with acute anterior myocardial infarction (MI) treated with direct PTCA.
One hundred patients were randomized to receive placebo (n=51) or a 40-mg intravenous bolus of the Na(+)/H(+) exchange inhibitor cariporide (HOE 642) (n=49) before reperfusion. Global and regional left ventricular functions were analyzed by use of paired contrast left ventriculograms performed before and 21 days after PTCA and myocardial enzymes (ie, creatine kinase ¿CK, CK-MB, and LDH) as markers for myocardial tissue injury were evaluated. At follow-up, the ejection fraction was higher (50% versus 40%; P<0.05) and the end-systolic volume was lower (69.0 versus 97.0 mL; P<0.05) in the cariporide group. Significant improvements in some indices of regional wall motion abnormalities were observed, such as the percentage of chords with hypokinesis < -2 SD (P=0.045) and the severity of hypokinesis in the border zone of the infarct region (P=0.052). In addition, CK, CK-MB, or LDH release was significantly reduced in the cariporide patients.
Our findings suggest that inhibition of Na(+)/H(+) exchange by cariporide may attenuate reperfusion injury and thereby improve the recovery from left ventricular dysfunction after MI.
心肌缺血和/或再灌注过程中钠氢交换体（Na(+)/H(+)）的激活会导致钙超载和心肌损伤。实验研究表明，钠氢交换体抑制剂可减少钙离子流入心肌细胞。因此，我们开展了一项多中心、随机、安慰剂对照的临床试验，以验证在接受直接经皮冠状动脉腔内血管成形术（PTCA）治疗的急性前壁心肌梗死（MI）患者中，抑制钠氢交换体能否限制梗死面积并改善心肌功能这一假设。
100例患者在再灌注前被随机分为两组，分别接受安慰剂治疗（n = 51）或静脉注射40 mg钠氢交换体抑制剂卡立泊来德（HOE 642）（n = 49）。通过PTCA术前及术后21天进行的配对对比左心室造影分析整体和局部左心室功能，并评估心肌酶（即肌酸激酶 - CK、CK - MB和乳酸脱氢酶）作为心肌组织损伤的标志物。随访时，卡立泊来德组的射血分数更高（50%对40%；P < 0.05），收缩末期容积更低（69.0对97.0 mL；P < 0.05）。观察到一些局部室壁运动异常指标有显著改善，如运动减弱＜ -2标准差的弦的百分比（P = 0.045）以及梗死区域边界区运动减弱的严重程度（P = 0.052）。此外，卡立泊来德治疗的患者中CK、CK - MB或LDH的释放显著减少。
我们的研究结果表明，卡立泊来德抑制钠氢交换体可能减轻再灌注损伤，从而改善心肌梗死后左心室功能障碍的恢复。
