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Mechanoenergetics in mechanically unloaded myocardial slices

机械卸载心肌切片中的机械能学

基本信息

批准号：
09670053
负责人：
TAKAKI Miyako
金额：
$ 1.86万
依托单位：
Nara Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

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.

老年人口增加，急性和慢性心血管疾病增加。因此，衰竭心脏的生理和病理生理方面是优先领域科学研究的重要问题。然而，人们对正常和衰竭心脏在逐搏基础上Ca^2+处理的能量效率知之甚少。整个心脏的机械能学研究表明，在衰竭心脏的发展过程中，存在O_2消耗效应或Ca^<2+>无效循环。为此，我们最近建立了一个新的测量系统的心肌O_2消耗量（V0_2）每分钟的机械卸载大鼠左心室（LV）切片。利用这个系统，我们揭示了电刺激引起的V0_2的增量（Δ V0_2）代表了在激子-收缩（E-C）耦合中处理0_2+的能量消耗。从显示2，3-丁二酮单肟（BDM）对Δ V0_2没有影响的结果，我们认为Δ V0_2不包含用于残余交叉桥循环的V0_2。我们还建立了一个测量系统片机械卸载收缩。这种收缩由运动指数表示。BDM大大降低了这一运动指数。该结果也支持Δ V0_2中不包括残余横桥循环的V0_2。我们还发现，V0_2无刺激代表的基础代谢，这是远远高于其他哺乳动物的心脏，并对应于在KCl-逮捕大鼠全心脏收缩。我们最终得到的结果显示，肌浆网（SR）Ga^<2+>泵阻断剂毒胡萝卜素和环匹阿尼酸并不降低基础代谢VO_2，但它们都使Δ VO_2降低了33%和68%，并使运动指数降低了63%和81%。我们认为，无负荷心肌V0_2由用于E-C偶联的V0_2和基础代谢的V0_2组成，而不包含用于残余横桥循环的V0_2。