Mechanoenergetics in mechanically unloaded myocardial slices

老年人口增加，急慢性心血管疾病增多。因此，心脏衰竭的生理和病理生理方面是科学研究的重点领域。然而，在正常心脏和衰竭心脏中，Ca^<2+>处理的能量效率在搏动基础上知之甚少。在衰竭心脏发育过程中，全心的力学能学表现为0_2损耗效应或Ca^<2+>无效循环。为此，我们建立了一种新的机械卸载大鼠左心室（LV）切片每分钟心肌耗氧量（V0_2）测量系统。利用该系统，我们揭示了电刺激引起的V0_2的增量（δ V0_2）代表了在激缩（E-C）耦合中处理0a2+的能量消耗。从2,3-丁二酮单肟（BDM）对V0_2无影响的结果来看，我们认为V0_2中不含V0_2。建立了切片机械卸载收缩测量系统。这种收缩用运动指数表示。BDM在很大程度上降低了这种运动指数。这一结果也支持了V0_2中不包含剩余过桥循环的V0_2。我们还发现，无刺激的V0_2表现出比其他哺乳动物心脏高得多的基础代谢，与kci停搏大鼠全心准备相对应。结果表明，肌浆网（SR） Ga^<2+>泵阻滞剂thapsigarin和cyclopiazonic acid虽不能降低基础代谢V0_2，但能使δ V0_2分别降低33%和68%，运动指数分别降低63%和81%。结果表明，心肌无负荷V0_2主要由E-C偶联和基础代谢的V0_2组成，不含剩余过桥循环的V0_2。

Increasing the population of elders, increasing acute and chronic cardiovascular diseases. Thus, physiological and pathophysiological aspects of failing hearts are important issue on Scientific Research on Priority Area. However, it is little known about the energetic efficiency of Ca^<2+> handling in normal and failing hearts on the beat to beat basis. Mechanoenergetics in whole hearts revealed an 0_2 wasting effect or Ca^<2+> futile cycling during the development of failing hearts. To this end, we have recently established a new measurement system of myocardial 0_2 consumption (V0_2) per min of mechanically unloaded rat left ventricular (LV)slices. Using this system, we have revealed that an increment in V0_2(delta V0_2) by electrical stiumulation represents energy expenditure for 0a2+ handling in the excitaiton-contraction (E-C) coupling. We consider that delta V0_2 does not contain V0_2 for residual cross-bridge cycling from the results showing no effect of 2,3-butanedione monoxime (BDM) on delta V0_2. We also established a measurement system slice mechanically unloaded contraction. This contraction is expressed by the motility index. BDM largely decreased this motility index. This result also supported no V0_2 for residual crossbridge cycling was included in delta V0_2. We also revealed that V0_2 without stimulation represents basal metabolism which is much higher than in other mammalian hearts and corresponds to that in the KCI-arrested rat whole heart prepartion. We finally obtained the results showing that sarcoplasmic reticulum (SR) Ga^<2+> pump blockers, thapsigargin and cyclopiazonic acid, did not reduce basal metabolic V0_2 but both of them reduced delta V0_2by 33 and 68% and reduced the motility index by 63 and 81%. We conclude that unloaded myocardial V0_2 is composed of V0_2 for E-C coupling and basal metabolism and does not contain V0_2 for residual crossbridge cycling.