ANESTHETIC INDUCED CARDIAC DEPRESSION

麻醉引起的心脏抑制

• 批准号: 3277187
• 负责人: BEN F RUSY
• 金额: $ 13万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-05-01 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3277187
• 关键词: anesthesia complication; anesthetics; calcium flux; drug adverse effect; electron probe spectrometry; enflurane; gas chromatography; guinea pigs; halothane; heart cell; heart contraction; heart disorder; heart surgery; inhalation anesthesia; isoflurane; laboratory rabbit; laboratory rat; lyophilization; microelectrodes; myocardium; sarcoplasmic reticulum; single cell analysis; tissue /cell culture

Large numbers of patients with advanced heart disease undergo anesthesia and surgery each year. Although the potent inhalational anesthetics such as halothane, enflurane, and isoflurane afford precise control of anesthetic depth and relatively rapid recovery, their use in these patients may be associated with inordinate depression of cardiac function. The mechanisms by which these potent anesthetics depress myocardial contractility is incompletely understood and antagonism of this depression is not satisfactorily accomplished with the presently available positive inotropic drugs. The scientific goal of the presently proposed research is to obtain an increased understanding of the mechanisms underlying anesthetic-induced depression of myocardial contractility. This is to be accomplished through a systematic study, in isolated intact myocardial tissue, of the effects of anesthetics on the subcellular physiologic processes which promote contraction and relaxation in the heart. A specific aim is to study the effects of anesthetics on the sources of the calcium ions which activate the contractile process. In particular, the way in which anesthetics affect calcium movements as well as the way in which these agents alter the internal cellular storage and release of calcium will be studied. Calcium ion selective microelectrodes will be employed to evaluate the effects of anesthetics on calcium movement into and out of the cell. Potentiated state contractions and rapid cooling contractures will be used to study anesthetic effects on cellular storage and release processes. Electron probe X-ray microanalysis will be used to determine the cellular content and location of calcium and the way in which these are affected by anesthetics. It is proposed that an increased understanding of the mechanisms which underlie anesthetic depression of myocardial contractility will facilitate rational methods for its reversal.

大量晚期心脏病患者接受 每年进行麻醉和手术。 虽然吸入性强 麻醉剂如氟烷、安氟烷和异氟烷 精确控制麻醉深度和相对较快的恢复， 它们在这些患者中的使用可能与过度治疗有关 心脏功能下降。 这些机制通过 强效麻醉药不完全抑制心肌收缩力 对这种抑郁症的理解和对抗并不令人满意 通过目前可用的正性肌力药物来完成。 目前提出的研究的科学目标是获得 加深对潜在机制的了解 麻醉药引起的心肌收缩力抑制。 这 是通过系统的研究、孤立的研究来完成的 完整的心肌组织，麻醉剂对心肌组织的影响 促进收缩和收缩的亚细胞生理过程 心中的放松。 一个具体的目标是研究其影响 麻醉剂对钙离子来源的影响 收缩过程。 特别是，其中的方式 麻醉剂影响钙的移动以及钙移动的方式 这些药物改变了细胞内部的储存和释放 将研究钙。 钙离子选择性微电极 将用于评估麻醉剂对钙的影响 进出细胞的运动。 强化状态收缩 快速冷却挛缩将用于研究麻醉 对细胞储存和释放过程的影响。 电子探针 X 射线微量分析将用于确定细胞含量 钙的位置以及它们受到影响的方式 麻醉剂。 建议加深对 心肌麻醉抑制的机制 收缩性将有助于采取合理的方法来逆转它。