van Meel J C, Entzeroth M, Redemann N, Haigh R M
Department of Biological Research, Dr. Karl Thomae GmbH, Biberachl Riss, Germany.
Arzneimittelforschung. 1995 Feb;45(2):136-41.
The effects of the cardiotonic agent pimobendan (CAS 118428-36-7, UD-CG 115 BS) and its main metabolite UD-CG 212 on dog cardiac myofibrillar calcium responsiveness and ATPase activity were studied at nominal free inorganic phosphate (Pi) and at 5 mmol/l Pi. A rightward shift of the pCa-tension relationship with a marked depression of maximal tension was observed in the presence of 5 mmol/l Pi. Pimobendan increased myofibrillar calcium responsiveness at concentrations > or = 10(-5) mol/l. These effects of pimobendan were significantly greater at 5 mmol/l Pi than at nominally free Pi. UD-CG 212 had no influence on myofibrillar calcium responsiveness at nominally free Pi, however, significant effects were observed at 10(-9) mol/l UD-CG 212 in the presence of 5 mmol/l Pi. UD-CG 212 (10(-8) mol/l) did not influence myofibrillar ATPase activity at pCa's 6.23, 5.99, and 4.36 with or without 5 mmol/l Pi, whereas pimobendan (10(-4) mol/l) had an effect only at pCa = 5.99 (without Pi) and pCa = 4.36 (+ 5 mmol/l Pi). The data suggest that the increase in myofibrillar calcium responsiveness at submaximal calcium concentrations by pimobendan and UD-CG 212 in the presence of 5 mmol/l Pi is brought about by a change in cross-bridge kinetics or by enhancement of thin filament activation by adjacent strong cross-bridges. At maximal calcium activation, pimobendan may additionally increase the population of strong cross-bridges.
在名义游离无机磷酸盐（Pi）以及5 mmol/L Pi条件下，研究了强心剂匹莫苯丹（化学物质登记号118428 - 36 - 7，UD - CG 115 BS）及其主要代谢产物UD - CG 212对犬心肌肌原纤维钙反应性和ATP酶活性的影响。在5 mmol/L Pi存在时，观察到pCa - 张力关系向右移位，最大张力显著降低。当匹莫苯丹浓度≥10⁻⁵ mol/L时，可增加肌原纤维钙反应性。在5 mmol/L Pi条件下，匹莫苯丹的这些作用比在名义游离Pi时显著更强。在名义游离Pi时，UD - CG 212对肌原纤维钙反应性无影响，然而，在5 mmol/L Pi存在时，10⁻⁹ mol/L的UD - CG 212可观察到显著作用。在有无5 mmol/L Pi的情况下，UD - CG 212（10⁻⁸ mol/L）对pCa为6.23、5.99和4.36时的肌原纤维ATP酶活性均无影响，而匹莫苯丹（10⁻⁴ mol/L）仅在pCa = 5.99（无Pi）和pCa = 4.36（+ 5 mmol/L Pi）时起作用。数据表明，在5 mmol/L Pi存在时，匹莫苯丹和UD - CG 212在亚最大钙浓度下增加肌原纤维钙反应性是由横桥动力学变化或相邻强横桥增强细肌丝激活所致。在最大钙激活时，匹莫苯丹可能还会增加强横桥的数量。
