Slinker B K, Green H W, Wu Y, Kirkpatrick R D, Campbell K B
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman 99164-6520, USA.
Am J Physiol. 1997 Dec;273(6):H2708-20. doi: 10.1152/ajpheart.1997.273.6.H2708.
Because it is not known whether ejection influences the negative effect of the Ca(2+)-sensitizing drugs on ventricular relaxation, we extended our previous analysis of stress-dependent relaxation in isovolumic beats to encompass ejecting beats and evaluated the relationships between both the time of onset of relaxation and the rate of relaxation and wall stress in a broader analysis framework. Furthermore, because the sites of action of the Ca(2+)-sensitizing drugs CGP-48506 and EMD-57033 may be different, and thus CGP-48506 may have fewer adverse effects on resting muscle length or force, we compared these two drugs to test the hypothesis that CGP-48506 would have less effect than EMD-57033 on relaxation in the isolated buffer-perfused rabbit heart. This analysis of stress-dependent relaxation in both ejecting and isovolumic beats readily differentiates between the negative lusitropic effect of 2 x 10(-6) M EMD-57033, the negligible lusitropic effect of 6 x 10(-6) M CGP-48506, and the positive lusitropic effect of 1.25 x 10(-6) M dobutamine. Furthermore, comparison of the effect of the two Ca(2+)-sensitizing drugs in ejecting versus isovolumic contractions shows that CGP-48506 affects relaxation differently in ejecting contractions than it does in isovolumic contractions, whereas EMD-57033 affects relaxation similarly in both ejecting and isovolumic contractions.
由于尚不清楚射血是否会影响钙增敏药物对心室舒张的负面影响，我们扩展了之前对等容搏动中应力依赖性舒张的分析，将射血搏动纳入其中，并在更广泛的分析框架内评估了舒张起始时间、舒张速率与壁应力之间的关系。此外，由于钙增敏药物CGP - 48506和EMD - 57033的作用位点可能不同，因此CGP - 48506对静息肌肉长度或力量的不良影响可能较小，我们比较了这两种药物，以检验CGP - 48506对离体缓冲液灌注兔心脏舒张的影响小于EMD - 57033的假设。对射血搏动和等容搏动中应力依赖性舒张的分析很容易区分2×10⁻⁶ M EMD - 57033的负性变时作用、6×10⁻⁶ M CGP - 48506可忽略不计的变时作用以及1.25×10⁻⁶ M多巴酚丁胺的正性变时作用。此外，比较两种钙增敏药物在射血收缩与等容收缩中的作用表明，CGP - 48506在射血收缩中对舒张的影响与在等容收缩中不同，而EMD - 57033在射血收缩和等容收缩中对舒张的影响相似。
