ANESTHETIC DEPRESSION OF THE MYOCARDIUM

心肌麻醉抑制

基本信息

批准号：
3278681
负责人：
THOMAS Joseph John BLANCK
金额：
$ 9.58万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1981
资助国家：
美国
起止时间：
1981-11-01 至 1989-03-31
项目状态：
已结题

项目摘要

Hypotension and cardiac arrest have been observed in patients anesthetized with the anesthetics halothane, enflurane, and isoflurane. These volatile anesthetics (VA's) are in wide clinical use today. Preliminary evidence suggests that the VA's might decrease the available of Ca2+ required for cardiac contraction. This project is designed to study the effect of the above mentioned anesthetics on structures in the myocardial cell that regulate Ca2+ flux and control the intensity of contraction. The elements that will be studied are: the sarolemma (SL), the outer membrane of the muscle cell; the sarcoplasmic reticulum (SR), a membranous network that controls the amount of myoplasmic Ca2+; the mitochondrion, the energy generating organelle which also serves to control tonic Ca2+ availability, and troponin (Tn), a protein that responds to Ca2+ binding by changing its shape and initiating the contractile process. Experiments will also be performed on isolated papillary muscles and myocytes to integrate the results found with the isolated subcellular structures with systems of more physiological complexity. Present evidence suggests that the SR and SL are affected by anesthetics and may be the major sites of alteration of contractility. The studies outlined will examine the interaction of halothane, enflurane, and isoflurane with the subcellular structures to observe alterations in Ca2+ response. The results will quantify the relative effect of each anesthetic on each structure and a possible mechanism of action will be postulated. The data obtained will help in formulating pharmacologic interventions to prevent anesthetic-induced cardiac depression in the operating room.

在麻醉患者中观察到低血压和心脏骤停与麻醉剂氟烷、安氟烷和异氟烷一起使用。这些挥发性麻醉剂（VA）如今在临床上广泛使用。初步证据表明 VA 可能会减少所需的 Ca2+ 的可用量心脏收缩。该项目旨在研究上述对心肌细胞结构的麻醉剂调节 Ca2+ 通量并控制收缩强度。元素将要研究的是：肌膜（SL），即细胞的外膜。肌细胞；肌浆网（SR），一个膜网络，控制肌质 Ca2+ 的量；线粒体，能量生成细胞器，也可以控制补品 Ca2+ 的可用性，肌钙蛋白 (Tn) 是一种通过改变其结构来响应 Ca2+ 结合的蛋白质形状并启动收缩过程。实验也将对分离的乳头肌和肌细胞进行整合结果发现，分离的亚细胞结构具有更多的系统生理复杂性。目前的证据表明 SR 和 SL 受麻醉剂的影响，可能是改变的主要部位收缩性。概述的研究将考察以下相互作用：氟烷、安氟烷和异氟烷的亚细胞结构观察 Ca2+ 反应的变化。结果将量化每种麻醉剂对每种结构的相对影响以及可能的影响将假设作用机制。获得的数据将有助于制定药物干预措施以预防麻醉引起的手术室里的心脏压抑。