ANESTHETIC-INDUCED CARDIAC PRECONDITIONING

麻醉诱导的心脏预处理

• 批准号: 6746026
• 负责人: Zeljko J. Bosnjak
• 金额: $ 121.14万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-05 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6746026
• 关键词: anesthetics; cytoprotection; heart electrical activity; heart pharmacology; myocardial ischemia /hypoxia

Research proposals developed in this Program Prqject will characterize the mechanisms responsible for the cardioprotective effects of volatile anesthetics against ischemia and reperfusion iniury in vivo, and will directly elucidate mechanisms regarding the specific signal transduction pathways modulated in vitro. It is our belief that the most effective approach to the complex and clinically relevant issue of myocardial ischemia and its response to anesthetics is to integrate our studies at multiple levels. We propose a Program Project consisting of three interrelated research projects supported by a Core facility focused on fundamental mechanisms responsible for the cardioprotective effects of volatile anesthetic-induced preconditioning (APC). This integrative approach will not only bring together a multi-talented group of investigators including cardiac electrophysiologists and molecular biologists, but also will capitalize on the unique advantage of interactions amongst the Cardiovascular Research Center, Biophysics Research Institute and the Departments of Pharmacology, Physiology, Biochemistry and Anesthesiology at the Medical College of Wisconsin. Project I. ANESTHETIC-INDUCED PRECONDITIONING IN VIVO. This project will delineate mechanisms responsible for the novel cardioprotective effects of volatile anesthetics against ischemia and reperfusion injury in vivo and will provide initial evidence for the involvement of specific signal transduction pathways modulating APC. Project Director: David C. Warltier, M.D., Ph.D. Project II. CARDIAC K,T, CHANNELS IN ANESTHETIC-INDUCED PRECONDITIONING. This prqject will investigate the effects of APC on the response of native sarcolemmal and mitochondfial KATp channels in cardiac ventricular myocytes, expressed recombinant KATp channels and channels in a lipid bilayer to nucleotides and potassium channel openers and blockers. Project Director: Zeljko J. Bosnjak, Ph.D. Project III. CARDIAC ELECTROPHYSIOLOGY IN ANESTHETIC-INDUCED PRECONDITIONING. This project will characterize arrhythmias and the ionic mechanisms underlying volatile anesthetic action on cardiac electrophysiology including major voltage-gated ion channel types (fast Na channel, L-type Ca channel, and transient outward K channel) that may ultimately be directly or indirectly involved in APC. Project Director: Wai-Meng Kwok, Ph.D. BIOCHEMICAL AND MOLECULAR BIOLOGY CORE. The Biochemical and Molecular Biology Core of this Program Prqiect will provide a highly specialized team of professional staff, capable of organizing a variety of assays in a well equipped facility to support investigation of hypotheses developed in Projects I, II and III. Core Directors: Meetha Medhora. Ph.D. and David Harder. Ph.D.

该计划中提出的研究建议将表征负责挥发性麻醉药对缺血和再灌注Iniury In Vivo的心脏保护作用的机制，并将直接阐明有关特定信号传递途径的机制。我们认为，对于心肌缺血的复杂和临床相关问题的最有效方法及其对麻醉剂的反应是将我们的研究在多个层面中整合。我们提出了一个计划项目，该项目由三个相互关联的研究项目组成，该项目由核心设施支持基本机制 负责挥发性麻醉诱导的预处理（APC）的心脏保护作用。这种综合方法不仅将汇集一组多才多艺的研究者，包括心脏电生理学家和分子生物学家，而且还将利用心血管研究中心之间的相互作用的独特优势。 项目I.麻醉诱导的体内预处理。该项目将描述负责挥发性麻醉药对缺血和体内再灌注损伤的新型心脏保护作用的机制，并将为调节APC的特定信号转导途径的参与提供初步证据。项目主任：M.D.，博士学位David C. Warltier 项目II。心脏K，T，通道麻醉引起的预处理。这 PRQject将研究APC对心室心肌细胞中天然肌膜和线粒体KATP通道的响应，在脂质双层中表达的重组KATP通道和通道对核苷酸和核苷酸和钾通道的响应。项目总监：Zeljko J. Bosnjak博士 项目三。麻醉诱导的预处理中的心脏电生理学。 该项目将表征心律不齐和挥发性的离子机制 对心脏电生理学的麻醉作用，包括主要电压门控通道类型（快速Na通道，L型CA通道和瞬态向外K通道），最终可能直接或间接参与APC。项目总监：Wai-Meng Kwok博士 生化和分子生物学核心。生化和分子生物学核心 在该计划中，PRQIECT将提供一支高度专业的专业员工团队，能够在设备齐全的设施中组织各种测定法，以支持对I，II和III项目中开发的假设的调查。核心主管：Meetha Medhora。博士大卫更努力。博士