METABOLIC REGULATION OF MYOCARDIAL CONTRACTILITY

这个项目的总体目标是确定调节 冠脉流量减少时的心肌收缩能力。这个目标 将通过测试下面的两部分假设来实现 离体兔心脏灌流： .冠脉流量轻度至中度减少。以冠脉流量计 在氧气利用率对ATP合成没有速率限制的情况下，变化 心肌中钙瞬变主要调节心肌细胞 伸缩性。 冠脉流量严重减少。在冠脉流速下，氧气 ATP合成的可用性是速度限制，无机的增加 磷酸盐(PI)和/或H+主要通过 降低肌丝钙敏感性。 为了验证这一假设，同时测量钙离子 瞬时、磷酸盐(ATP、磷酸肌酸、PI)、细胞内pH和 在稳态降低心肌收缩能力的过程中 冠脉血流和急性无血流状态。钙瞬变将是 使用Indo-1，一种荧光钙指示剂进行测量。磷酸盐和 细胞内的pH值将使用31P核磁共振波谱进行测量。建议数 实验将提供新的和重要的信息 冠脉流量减少时调节收缩能力的机制。

The overall goal of this project is to determine the factors that regulate myocardial contractility during reductions of coronary flow. This goal will be accomplished by testing the following two-part hypothesis in isolated perfused rabbit hearts: .mild to moderate reductions of coronary flow. At coronary flow rates where oxygen availability is not rate-limiting for ATP synthesis, changes in the myocardial calcium transient primarily regulate myocardial contractility. .severe reductions of coronary flow. At coronary flow rates where oxygen availability is rate limiting for ATP synthesis, increases of inorganic phosphate (Pi) and/or H+ primarily regulate myocardial contractility by decreasing myofilament calcium sensitivity. To test this hypothesis, simultaneous measurements of the calcium transient, phosphates (ATP, phosphocreatine, Pi), intracellular pH, and myocardial contractility will be made during steady-state reductions of coronary flow and acute no-flow conditions. The calcium transient will be measured using indo-1, a fluorescent calcium indicator. Phosphates and intracellular pH will be measured using 31P NMR spectroscopy. The proposed experiments will provide new and important information regarding the mechanisms that regulate contractility during reductions of coronary flow.