de Tombe P P, Burkhoff D, Hunter W C
Department of Biomedical Engineering, Johns Hopkins University, School of Medicine, Baltimore, Md. 21205.
Circulation. 1992 Dec;86(6):1945-54. doi: 10.1161/01.cir.86.6.1945.
Most positive inotropic agents increase cardiac contractility by increasing the amount of Ca2+ cycled with each beat. The additional amount of oxygen that is consumed by the heart to cycle this additional Ca2+ is believed to reduce myocardial efficiency. On the other hand, it has been suggested that the agent EMD-53998 increases the Ca2+ sensitivity of the contractile proteins without affecting the intracellular Ca2+ transient in cardiac muscle. Therefore, application of this agent may increase cardiac contractility without decreasing myocardial efficiency. The purpose of the present study was to test this hypothesis.
We measured myocardial oxygen consumption (MVO2) in six isolated, isovolumically beating blood-perfused canine hearts. The hearts were paced at 120 beats per minute. Contractility was varied in each heart by infusion of either CaCl2 or EMD-53998. With infusion of either agent, MVO2 was a linearly proportional function of contractility. No significant difference between CaCl2 and EMD-53998 could be detected in the interrelation between contractility and MVO2.
We conclude that the "calcium-sensitizing agent" EMD-53998 is a potent positive inotropic agent in the isolated, blood-perfused canine heart. However, EMD-53998 does not provide an energetic advantage over currently used positive inotropic agents.
大多数正性肌力药物通过增加每次心跳循环的Ca2+量来增强心肌收缩力。心脏为循环这些额外的Ca2+而消耗的额外氧量被认为会降低心肌效率。另一方面，有人提出EMD - 53998药物可增加收缩蛋白对Ca2+的敏感性，而不影响心肌细胞内Ca2+瞬变。因此，应用该药物可能增加心肌收缩力而不降低心肌效率。本研究的目的是验证这一假设。
我们在6个离体、等容搏动、血液灌注的犬心脏中测量了心肌耗氧量（MVO2）。心脏以每分钟120次心跳起搏。通过输注氯化钙或EMD - 53998改变每个心脏的收缩力。输注任何一种药物时，MVO2都是收缩力的线性比例函数。在收缩力与MVO2的相互关系中，未检测到氯化钙和EMD - 53998之间有显著差异。
我们得出结论，“钙敏化剂”EMD - 53998在离体、血液灌注的犬心脏中是一种有效的正性肌力药物。然而，与目前使用的正性肌力药物相比，EMD - 53998在能量利用方面并无优势。
