PHASE RESETTING OF CIRCUS MOVEMENT REENTRY

马戏团运动再入阶段的重置

• 批准号: 3358037
• 负责人: Robert F Gilmour
• 金额: $ 11.62万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3358037
• 关键词: acetylcholine; antiarrhythmic agent; autonomic agents; calcium channel; dogs; electrophysiology; heart Purkinje's fiber; heart pharmacology; isoproterenol; lidocaine; microelectrodes; neurotransmitters; nitrendipine; tetrodotoxin; ventricular fibrillation; verapamil

Circus movement reentry commonly has been invoke as a mechanism for ventricular arrhythmias, yet the modes of initiation and perpetuation of reentry remain the subject of considerable debate and conjecture. The purpose of these studies is to identify the determinants of reentry and Purkinje-muscle junctions (PMJ) and to establish the mechanisms by which subthreshold electrical stimuli,ionic channel blocking agents and autonomic neurotransmitters modulate Purkinje-muscle reentry. These studies will utilize branched Purkinje-muscle preparations mounted in a partitioned bath. One PMJ will be superfused with normal Tyrode solution and the other PMJ will be superfused with a hyperkalemic, hypoxic and acidotic Tyrode solution. Multiple microelectrode recordings will be obtained simultaneously from both PMJs. The projected components of the reentry circuit are: a premature or postmature initiating stimulus; unidirectional anterograde conduction block at the PMJ superfused with altered Tyrode solution; circulation of the impulse around the functional obstacle crated by lack of electrical coupling between Purkinje and muscle cells except at the PMJ and ; marked retrograde activation delay and reentry at the previously blocked PMJ. The proposed mechanisms for these events are that reflection across the PMJ generates a premature stimulus that subsequently initiates reentry, where as time-dependent reduction of action potential amplitude, mediated by recovery of the early outward current, causes PMJ conduction block and the subsequent development of reentry following a postmature stimulus. Conduction block at the PMJ during attempted anterograde conduction is caused by the large electrical load, or sink to the large source generated by muscle. Drugs and neurotransmitters that alter the relationship between source and sink may facilitate or suppress reentry accordingly. Further experiments will test the hypothesis that sustained Purkinje-muscle reentry represents a biological oscillator whose period can be advanced, delayed, entrained or annihilated by properly timed subthreshold stimuli delivered to the PMJ. Phase plane trajectories of the reentry circuit will be analyzed to gain insights concerning the nonlinear behavior of reentry. These studies promise to define the mechanisms by which reentry is initiated and sustained and to suggest new ways whereby reentry can be modified.

马戏运动的再入通常被作为一种机制来调用