Schwinger R H, Müller-Ehmsen J, Frank K, Koch A, Erdmann E
Medizinische Klinik III, Universitat zu Köln, Germany.
Am Heart J. 1996 May;131(5):988-93. doi: 10.1016/s0002-8703(96)90184-2.
Cardiac glycosides and Na+ -channel activators increase intracellular Na+ and thereby enhance the transport rate of the sarcolemmal Na+/Ca2+ exchanger. We tested the hypothesis of whether increased expression of the Na+/Ca2+ exchanger in failing human myocardium is accompanied by enhanced sensitivity of the failing human myocardium toward cardiac glycosides and Na+ -channel activators. We studied the positive inotropic effects of the new Na+ -channel activator BDF and the cardiac glycoside ouabain in human failing (New York Heart Association [NYHA] functional class IV, heart transplants for dilated cardiomyopathy, n = 11) and nonfailing (donor hearts, n = 5) myocardium on electrically driven left ventricular papillary muscle strips (1 Hz, 37 degrees C). The effectiveness of ouabain and BDF to increase force of contraction was similar in human nonfailing and failing myocardium. BDF was more potent to increase force of contraction in failing than in nonfailing tissue (p < 0.05). The time until maximal inotropic effect developed after ouabain was significantly shorter in NYHA IV (mean 150 +/- 16 min) than in nonfailing myocardium (mean 240 +/- 20 min). These results suggest that human failing myocardium exerts and enhanced sensitivity to cardiac glycosides and Na+ -channel activators, possibly because of enhanced expression of the Na+/Ca2+ exchanger or because of an altered intracellular Na+ -homeostasis.
强心苷和钠离子通道激活剂可增加细胞内钠离子浓度，从而提高肌膜钠钙交换体的转运速率。我们检验了以下假设：在衰竭的人类心肌中，钠钙交换体表达增加是否伴随着衰竭的人类心肌对强心苷和钠离子通道激活剂的敏感性增强。我们研究了新型钠离子通道激活剂BDF和强心苷哇巴因对人类衰竭（纽约心脏协会[NYHA]心功能IV级，因扩张型心肌病接受心脏移植，n = 11）和非衰竭（供体心脏，n = 5）心肌电驱动左心室乳头肌条（1 Hz，37℃）的正性肌力作用。哇巴因和BDF增加收缩力的有效性在人类非衰竭和衰竭心肌中相似。BDF在衰竭组织中增加收缩力的效力比在非衰竭组织中更强（p < 0.05）。NYHA IV级患者在给予哇巴因后达到最大正性肌力作用的时间（平均150 +/- 16分钟）明显短于非衰竭心肌（平均240 +/- 20分钟）。这些结果表明，人类衰竭心肌对强心苷和钠离子通道激活剂的敏感性增强，可能是由于钠钙交换体表达增加或细胞内钠稳态改变所致。
