PHASE RESETTING OF CIRCUS MOVEMENT REENTRY

马戏团运动再入阶段的重置

• 批准号: 3358039
• 负责人: Robert F Gilmour
• 金额: $ 12.24万
• 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/3358039
• 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.

回旋运动折返通常被认为是一种机制， 室性心律失常，然而， 重返大气层仍然是一个相当大的争论和猜测的主题。 的 这些研究的目的是确定再入大气层的决定因素， 浦肯野-肌肉连接（PMJ），并建立机制， 阈下电刺激、离子通道阻滞剂和自主神经刺激 神经递质调节浦肯野肌折返。 这些研究将 利用分支浦肯野-肌肉准备安装在一个分区， 浴 一个PMJ将用标准Tyrode溶液灌注，另一个PMJ将用标准Tyrode溶液灌注。 PMJ将灌注高钾、缺氧和酸中毒的台罗德 溶液 将获得多个微电极记录 两个PMJ同时 重返大气层的预计部分 回路是：过早或过熟的起始刺激;单向的 经改良台氏液灌注的PMJ处的顺行传导阻滞 解决方案;脉冲在功能障碍物周围的循环 由于浦肯野细胞和肌肉细胞之间缺乏电耦合， PMJ和;显著的逆行激活延迟和折返， 此前，PMJ。 这些事件的拟议机制是， 穿过PMJ的反射产生过早的刺激， 启动折返，其中作为动作电位的时间依赖性降低 由早期外向电流的恢复介导的振幅引起PMJ 传导阻滞和随后的折返发展， 过熟刺激 尝试时PMJ传导阻滞 顺行传导是由大的电负荷引起的，或汇至 肌肉产生的大量能量源。 药物和神经递质 改变源和汇之间的关系可以促进或抑制 相应的回归。 进一步的实验将检验这一假设， 持续的浦肯野肌折返代表了一种生物振荡器， 一个时期可以提前，延迟，夹带或消灭， 传递到PMJ的阈下刺激。 相平面轨迹 将分析再入电路，以获得有关非线性的见解 再入行为。 这些研究承诺通过以下方式来定义机制： 这种再入是启动和维持的，并提出了新的方法， 可以修改再入。