Mechanoenergetics in mechanically unloaded myocardial slices

老年人口增加，急慢性心血管疾病增加。因此，心力衰竭的生理和病理生理学方面是重点领域科学研究的重要课题。然而，对于正常心脏和衰竭心脏在节拍的基础上处理钙离子的能量效率，人们知之甚少。整个心脏的机械能量学表明，在衰竭心脏的发育过程中，存在0_2损耗效应或Ca~(2+)无效循环。为此，我们最近建立了一种新的心肌耗氧量(VO_2)/分钟测量系统。利用这一系统，我们揭示了在激子-收缩(E-C)耦合过程中，电沉积值V0_2(增量V0_2)的增加代表了0a2+处理的能量消耗。从2，3-丁二酮单肟(BDM)对Delta V0_2无影响的结果中，我们认为对于剩余过桥循环而言，Delta V0_2不包含V0_2。我们还建立了切片机械无负荷收缩的测量系统。这种收缩是由运动指数来表示的。BDM显著降低了这一运动指数。这一结果也支持没有V0_2，因为剩余的交叉桥循环包含在增量V0_2中。我们还发现，在没有刺激的情况下，V0_2代表的基础代谢远高于其他哺乳动物心脏，与KCI停搏大鼠全心准备中的V0_2相对应。结果表明，肌浆网泵阻滞剂thapsigargin和clopiazonic不降低基础代谢物V0_2，但两者分别使V0_2降低33%和68%，运动指数降低63%和81%。我们认为，去负荷心肌V0_2由E-C偶联和基础代谢的VO_2组成，不含剩余跨桥循环的VO_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.