Näbauer M, Böhm M, Brown L, Diet F, Eichhorn M, Kemkes B, Pieske B, Erdmann E
Medizinische Klinik I, Universität München, FRG.
Eur J Clin Invest. 1988 Dec;18(6):600-6. doi: 10.1111/j.1365-2362.1988.tb01274.x.
The positive inotropic responses to isoprenaline, dobutamine, histamine, forskolin, isobutyl-methylxanthine (IBMX), dibutyryl-cyclic adenosine monophosphate (db-cAMP), ouabain and calcium were studied in isolated, electrically driven papillary muscle strips from either terminally failing human hearts or non-failing donor myocardium. The positive inotropic effect of calcium has been taken to evaluate the maximal force of contraction of each individual muscle strip ('contractile reserve'). In the non-failing heart, the maximal positive inotropic effect of isoprenaline, dobutamine, IBMX, ouabain and calcium were not significantly different, but were significantly greater than histamine. In terminally failing hearts, the positive inotropic effects of agents stimulating the adenylate cyclase by a receptor-dependent mechanism (isoprenaline, dobutamine and histamine) and the phosphodiesterase inhibitor IBMX are less than in the normal heart. Furthermore, these compounds gave a markedly reduced inotropic effect compared with forskolin, db-cAMP and ouabain, which gave maximal responses similar to calcium in the failing hearts. The data did not differ when the increase of force of contraction was related to the diameter of each preparation. These results indicate that a defect in adenylate cyclase occurs in the failing human heart, presumably located at the regulatory stimulatory subunit (Gs) of the adenylate cyclase since effects through stimulatory receptors were reduced. Responses from activation of the catalytic subunit or through cAMP-dependent protein kinases were less affected. Since the positive inotropic effect of IBMX is also impaired, it is suggested that the basal rate of cAMP production is also reduced in heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
在来自晚期衰竭的人类心脏或非衰竭供体心肌的离体电驱动乳头肌条中，研究了对异丙肾上腺素、多巴酚丁胺、组胺、福斯高林、异丁基甲基黄嘌呤（IBMX）、二丁酰环磷酸腺苷（db - cAMP）、哇巴因和钙的正性肌力反应。钙的正性肌力作用已被用于评估每条单独肌肉条的最大收缩力（“收缩储备”）。在非衰竭心脏中，异丙肾上腺素、多巴酚丁胺、IBMX、哇巴因和钙的最大正性肌力作用无显著差异，但显著大于组胺。在晚期衰竭心脏中，通过受体依赖性机制刺激腺苷酸环化酶的药物（异丙肾上腺素、多巴酚丁胺和组胺）以及磷酸二酯酶抑制剂IBMX的正性肌力作用小于正常心脏。此外，与福斯高林、db - cAMP和哇巴因相比，这些化合物的正性肌力作用明显降低，而福斯高林、db - cAMP和哇巴因在衰竭心脏中产生的最大反应与钙相似。当收缩力的增加与每个制剂的直径相关时，数据没有差异。这些结果表明，衰竭的人类心脏中发生了腺苷酸环化酶缺陷，可能位于腺苷酸环化酶的调节性刺激亚基（Gs），因为通过刺激受体的作用减弱了。催化亚基激活或通过cAMP依赖性蛋白激酶的反应受影响较小。由于IBMX的正性肌力作用也受损，提示心力衰竭时cAMP的基础产生率也降低。（摘要截短于250字）
