PHYSIOLOGY OF HYPERPOLARIZED CARDIOPLEGIC ARREST

超极化心脏停搏的生理学

• 批准号: 2214343
• 负责人: A MARK JAYAWANT
• 金额: $ 2.86万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-10 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2214343
• 关键词: PHYSIOLOGY; HYPERPOLARIZED; CARDIOPLEGIC; ARREST

Modern techniques of myocardial preservation during cardiac surgery involve the use of hyperkalemic cardioplegia which induces depolarized arrest. Morbidity and mortality following cardiac operations has decreased significantly with the advent of these solutions. Although effective, there remain inherent drawbacks associated with potassium cardioplegia which result in a significant incidence of postoperative cardiac arrhythmias and conduction abnormalities. The goal of this research project is to study an alternative, more physiologic form of cardioplegia based on the mechanism of hyperpolarized arrest. It is our hypothesis that hyperpolarizing the myocyte to achieve arrest at an electrochemical potential that resembles the myocyte at rest will eliminate the compensatory metabolic processes and abnormal transmembrane ionic gradients observed at depolarized membrane potentials. Hyperpolarized arrest will be studied in the isolated heart model and in the intact porcine model, using functional, electrophysiologic, and histologic criteria. Hyperpolarized arrest will be induced by potassium channel openers (PCOs). PCOs are a class of compounds which open ATP- sensitive potassium channels in the heart. These channels have been shown to have a natural cardioprotective effect by opening to hyperpolarize the membrane and shorten the action potential in times of ATP depletion. The use of PCOs, therefore, may avoid significant reperfusion injury and replace potassium cardioplegia in the induction of elective cardiac arrest.

心脏手术期间心肌保存的现代技术 涉及诱导去极化的高钾血症患者的使用 逮捕。 心脏操作后的发病率和死亡率具有 随着这些解决方案的出现，大大减少了。 虽然 有效，仍然存在与钾有关的固有缺点 术后大量发病率很大 心律不齐和传导异常。 目标的目标 研究项目是研究一种替代性，更生理的形式 心脏病基于超极化停滞的机制。 这是我们的 假设超极化心肌以在 类似于静止的心肌的电化学潜力将 消除代偿代谢过程和异常跨膜 在去极化膜电位上观察到的离子梯度。 超极化逮捕将在孤立的心脏模型和 完整的猪模型，使用功能，电生理学和 组织学标准。 钾将诱导超极化逮捕 频道开启器（PCOS）。 PCOS是一类打开ATP-的化合物 心脏中敏感的钾通道。 这些渠道已经 通过开放，证明具有自然的心脏保护作用 超极化膜并缩短动作电位 ATP耗竭。 因此，PCOS的使用可能会避免明显 再灌注损伤并替换诱导中的钾心杂志 心脏骤停。