ANESTHETIC INDUCED CARDIAC DEPRESSION

麻醉引起的心脏抑制

• 批准号: 3277185
• 负责人: BEN F RUSY
• 金额: $ 9.7万
• 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 1991-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3277185
• 关键词: anesthetics; calcium transporting ATPase; drug adverse effect; general anesthesia; guinea pigs; heart contraction; heart pharmacology; laboratory rabbit; laboratory rat; sarcoplasmic reticulum

Large numbers of patients with advanced heart disease undergo anesthesia and surgery each year. Methods of safely anesthetizing these patients are available, but they are frequently associated with delayed emergence and a prolonged period of respiratory depression requiring mechanically assisted ventilation, often in an intensive care setting. The use of the potent inhalation agents in these patients would be ideal from the standpoint of affording a more rapid recovery. However, cardiac contractile depression with these anesthetics can be appreciable and can result in dangerous depression of circulatory function. Antagonism of the depression of cardiac function caused by the potent agents is not readily accomplished with the presently available cardiotonic drugs because of side effects, such as dysrhythmias, associated with their use. It is proposed that a better understanding of the mechanisms which underlie anesthetic-induced negative inotropy will facilitate the development of rational methods for its reversal. The general scientific goals of the presently proposed research are to perform, in isolated, intact, cardiac contractile tissue, a systematic investigation of the effects of general anesthetics on the steps in electromechanical coupling which result in contraction, and to investigate methods for reversing such depression. Specific aims are to study the effects of anesthetics on the sources of calcium which activate contraction, i.e. on the calcium which is derived via transsarcolemmal influx and via intracellular release from the sarcoplasmic reticulum. Determination of the effect of an anesthetic on a particular source of activator calcium will be accomplished by measuring the anesthetic's effect on contractile performance under conditions which inhibit, or enhance the influence of the particular source of calcium on the activation of contraction. Calcium selective microelectrodes will be used to evaluate the effect of anesthetics on calcium movement (calcium influx) during contraction under these conditions. It is expected that knowledge concerning the differential effects of anesthetics on the calcium will suggest which of the several newly developed positive inotropic agents will be effective in reversing their specific negative inotrophic effects. Studies employing these agents will be performed.

大量晚期心脏病患者接受 每年进行麻醉和手术。 安全麻醉的方法 这些患者是可用的，但他们经常与 出现延迟且呼吸时间延长 需要机械辅助通气的抑郁症，通常发生在 重症监护室。 使用强效吸入剂 从负担得起的角度来看，对这些患者来说是理想的 更快的恢复。 然而，心脏收缩抑制 使用这些麻醉剂的效果可能会很明显，并可能导致 危险的循环功能抑制。 的对抗 强效药物引起的心功能抑制不是 使用目前可用的强心药物很容易实现 因为副作用，例如心律失常， 他们的用途。 建议更好地理解 麻醉引起的负性肌力的机制 促进开发合理的方法来逆转它。 目前提出的研究的总体科学目标是 在孤立的、完整的心脏收缩组织中执行 全身麻醉对患者影响的系统研究 机电耦合的步骤导致 收缩，并研究逆转这种收缩的方法 沮丧。 具体目标是研究麻醉剂的效果 关于激活收缩的钙的来源，即 钙是通过肌膜流入和通过 肌浆网的细胞内释放。 确定麻醉剂对特定来源的影响 活化剂钙的测定将通过测量 麻醉剂在一定条件下对收缩性能的影响 抑制或增强特定来源的影响 钙对收缩的激活作用。 钙选择性 微电极将用于评估麻醉剂的效果 在这些条件下收缩期间的钙运动（钙流入） 状况。 预计有关的知识 麻醉剂对钙的不同影响将表明 几种新开发的正性肌力药物中哪一种将 有效逆转其特定的负性肌营养不良 影响。 将进行使用这些药物的研究。