Schwinger R H, Böhm M, La Rosée K, Schmidt U, Schulz C, Erdmann E
Medizinische Klinik I, Universität München, Klinikum Grosshadern, Germany.
J Cardiovasc Pharmacol. 1992 Apr;19(4):554-61. doi: 10.1097/00005344-199204000-00012.
Na(+)-channel activators increase intracellular Na+ and thereby enhance the transport rate of sarcolemmal Na+,K(+)-ATPase. We investigated the interaction of the new Na(+)-channel activator BDF 9148 (BDF) with the cardiac glycoside ouabain (OUA) in human myocardium. The influence of OUA (0.01-0.1 microM) and of OUA after prestimulation with BDF (0.1 microM, 1 microM; BDF+OUA) on isometric force of contraction (FOC, force of contraction; +T/-T, peak rate of tension increase/decay) of electrically driven (1 Hz, 37 degrees C) papillary muscle strips from terminally failing [New York Heart Association classification IV (NYHA IV) heart transplants, n = 19] human myocardium was studied. We also examined the effects of BDF and OUA on nonfailing human myocardium (brain death resulting from traumatic injury, n = 5). 0.01 microM OUA enhanced FOC only after prestimulation with BDF (NYHA IV+2.9 +/- 0.4 mN; p less than 0.01). The time until maximal (Tmax: BDF+OUA 117 min, OUA 166 min), half-maximal (T1/2max: BDF+OUA 47 min, OUA 85 min) inotropic effects and time until toxic signs (contracture, extrasystoles) occurred were significantly shorter with BDF+OUA as compared with OUA alone. BDF influenced Tmax, T1/2max, and time until toxic side effects occurred (Ttox) of the OUA-mediated inotropism in a concentration-dependent manner. Both OUA and BDF enhanced +T and -T. The effectiveness of OUA and BDF in increasing FOC was similar to that of Ca2+ (1.8-15 mM) but significantly (p less than 0.01) higher as compared with the beta-adrenoceptor-agonist isoprenaline in NYHA IV. In myocardial membranes, [3H]ouabain binding (Bmax, Kd) was not affected by BDF.(ABSTRACT TRUNCATED AT 250 WORDS)
钠离子通道激活剂可增加细胞内钠离子浓度，从而提高肌膜钠钾ATP酶的转运速率。我们研究了新型钠离子通道激活剂BDF 9148（BDF）与人心肌中强心苷哇巴因（OUA）的相互作用。研究了OUA（0.01 - 0.1微摩尔）以及先用BDF（0.1微摩尔、1微摩尔；BDF + OUA）预刺激后再用OUA对终末期心力衰竭[纽约心脏协会心功能分级IV级（NYHA IV）心脏移植，n = 19]患者的电驱动（1赫兹，37摄氏度）乳头肌条等长收缩力（FOC，收缩力；+T/-T，张力增加/衰减的峰值速率）的影响。我们还研究了BDF和OUA对非衰竭人心肌（因创伤性损伤导致脑死亡，n = 5）的影响。仅在先用BDF预刺激后，0.01微摩尔的OUA才增强FOC（NYHA IV级增加2.9±0.4毫牛顿；p < 0.01）。与单独使用OUA相比，BDF + OUA达到最大正性肌力作用的时间（Tmax：BDF + OUA为117分钟，OUA为166分钟）、达到半最大正性肌力作用的时间（T1/2max：BDF + OUA为47分钟，OUA为85分钟）以及出现毒性体征（挛缩、早搏）的时间明显更短。BDF以浓度依赖的方式影响OUA介导的正性肌力作用的Tmax、T1/2max以及出现毒性副作用的时间（Ttox）。OUA和BDF均增强了+T和 -T。在NYHA IV级患者中，OUA和BDF增加FOC的效果与钙离子（1.8 - 15毫摩尔）相似，但与β肾上腺素能受体激动剂异丙肾上腺素相比显著更高（p < 0.01）。在心肌膜中，[3H]哇巴因结合（Bmax、Kd）不受BDF影响。（摘要截短至250字）
