The positive inotropic effects of the dihydropyridine calcium activator Bay K 8644 were studied in guinea-pig isolated contracting myocardium and human papillary muscle strips obtained from patients undergoing mitral valve replacement or cardiac transplantation. 2. Bay K 8644 produced a slowly developing, concentration-dependent positive inotropic response in all cardiac tissues studied. In guinea-pig papillary muscle, the increase in force of contraction was half-maximal at 3.9 x 10(-8) mol/l and the maximal inotropic effect was comparable to that obtained with ouabain, dobutamine or calcium. The guinea-pig left atrium (EC50, 2.1 x 10(-7) mol/l) was fivefold less sensitive than the papillary muscle. 3. The maximal inotropic response to dihydroouabain was significantly increased after preincubation with Bay K 8644 (1 x 10(-6) mol/l) in papillary muscles from both guinea-pig and human. In guinea-pig papillary muscles, the maximal inotropic response to dobutamine was not changed by preincubation with Bay K 8644 whereas in human papillary muscle strips, Bay K 8644 increased the inotropic response to dobutamine. 4. Bay K 8644 increased force of contraction (EC50, 4 x 10(-8) mol/l) in human papillary muscle strips from patients undergoing mitral valve replacement. However, the maximal inotropic response to Bay K 8644 was reduced to 32 +/- 4.4% that of calcium (15 mmol/l) measured in the same muscle strips. 5. A further reduction in maximal inotropic response to Bay K 8644 to 13 +/- 1.2% that of calcium (15 mmol/l) with no change in potency was measured in human papillary muscle strips taken from terminally failing hearts of cardiac transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
摘要
在豚鼠离体收缩心肌以及从接受二尖瓣置换术或心脏移植的患者获取的人乳头肌条上，研究了二氢吡啶类钙激活剂Bay K 8644的正性肌力作用。2. Bay K 8644在所有研究的心脏组织中产生了缓慢发展的、浓度依赖性的正性肌力反应。在豚鼠乳头肌中，收缩力增加的半数有效浓度为3.9×10⁻⁸mol/L，最大正性肌力作用与哇巴因、多巴酚丁胺或钙所产生的相当。豚鼠左心房（半数有效浓度为2.1×10⁻⁷mol/L）的敏感性比乳头肌低五倍。3. 在豚鼠和人的乳头肌中，用Bay K 8644（1×10⁻⁶mol/L）预孵育后，对二氢哇巴因的最大正性肌力反应显著增加。在豚鼠乳头肌中，用Bay K 8644预孵育对多巴酚丁胺的最大正性肌力反应无改变，而在人乳头肌条中，Bay K 8644增加了对多巴酚丁胺的正性肌力反应。4. Bay K 8644增加了二尖瓣置换术患者人乳头肌条的收缩力（半数有效浓度为4×10⁻⁸mol/L）。然而，在相同肌条中测得的对Bay K 8644的最大正性肌力反应降至钙（15mmol/L）的32±4.4%。5. 在取自心脏移植受者终末期衰竭心脏的人乳头肌条中，测得对Bay K 8644的最大正性肌力反应进一步降至钙（15mmol/L）的13±1.2%，效价无变化。（摘要截短于250字）
