Erdmann E, Böhm M
Medizinische Klinik I, University of Munich, Klinikum Grosshadern, München, FRG.
Basic Res Cardiol. 1989;84 Suppl 1:125-33. doi: 10.1007/BF02650352.
Cardiac alpha- and beta-adrenoceptors and the positive inotropic effects of several adenylate cyclase dependent and independent agents have been measured in papillary muscle strips from patients without, as well as with moderate and severe heart failure. The number of beta-adrenoceptors was found to be decreased depending on the degree of heart failure. This does not apply to alpha-adrenoceptors, which remain unchanged. The antagonist affinity of adrenoceptors for the different ligands did not change in heart failure. Maximal increases in force of contraction were measured after raising Ca++ up to 15 mM in the muscle strips. In healthy human myocardium, isoprenaline, dobutamine, IBMX or cardiac glycosides increase force of contraction to the same maximal values as Ca++ does. However, in cardiac tissue from heart failure patients, positive inotropic agents which increase intracellular cAMP or are cAMP-dependent are less effective than Ca++. Furthermore, the results seem to indicate a homologous (agonist specific) downregulation of receptors in moderate heart failure and a heterologous downregulation in severe heart failure. Thus, many well known positive inotropic drugs lose their effectiveness just when they are needed most: in severe heart failure.
在无心力衰竭以及患有中度和重度心力衰竭患者的乳头肌条中，已对心脏α和β肾上腺素能受体以及几种依赖和不依赖腺苷酸环化酶的药物的正性肌力作用进行了测量。发现β肾上腺素能受体的数量根据心力衰竭的程度而减少。这不适用于保持不变的α肾上腺素能受体。心力衰竭时，肾上腺素能受体对不同配体的拮抗剂亲和力没有改变。在肌条中将Ca++浓度提高到15 mM后，测量了收缩力的最大增加。在健康人的心肌中，异丙肾上腺素、多巴酚丁胺、异丁基甲基黄嘌呤（IBMX）或强心苷增加收缩力的最大值与Ca++相同。然而，在心力衰竭患者的心脏组织中，增加细胞内cAMP或依赖cAMP的正性肌力药物的效果不如Ca++。此外，结果似乎表明中度心力衰竭中存在受体的同源（激动剂特异性）下调，重度心力衰竭中存在异源下调。因此，许多众所周知的正性肌力药物恰好在最需要它们的时候失去效力：在重度心力衰竭中。
