COCAINE-INDUCED VENTRICULAR FIBRILLATION

可卡因引起的心室颤动

• 批准号: 3212504
• 负责人: GEORGE Edward BILLMAN
• 金额: $ 12.5万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3212504
• 关键词: adrenergic receptor; calcium flux; cocaine; dogs; drug administration rate /duration; drug administration routes; drug adverse effect; drug withdrawal; exercise; heart circulation; heart electrical activity; heart pharmacology; hemodynamics; myocardial ischemia /hypoxia; second messengers; ventricular fibrillation

The increasing popularity and widespread use of cocaine has reached epidemic proportions. Accompanying the increase in cocaine abuse has been an escalation in the number of cocaine related emergency room visits, hospital admissions and deaths. Indeed, there is increasing evidence that cocaine can provoke lethal cardiovascular events including stroke, myocardial infarction, and malignant cardiac rhythm disorders such as ventricular fibrillation (VF). In spite of the growing association between lethal cardiac events, relatively little is known about the mechanisms precipitating these cardiovascular event, particularly VF. It is well established that cocaine can enhance the effects of adrenergic stimuli which are, in turn, known to reduce cardiac electrical stability. The mechanism by which enhanced adrenergic activity contributes to VF is not known. Ultimately activation of adrenergic receptors must evoke a variety of cellular responses in the cardiac tissue. These alterations within the cardiac cells could contribute significantly to the development of VF. It is therefore the purpose of the proposed series of experiments to: a) investigate the effects of cocaine on cardiac electrical stability; b) determine the role that cocaine-induced increases in adrenergic activity play in VF; c) determine the role that intracellular mediators of cocaine play in VF; and d) investigate the hemodynamic effects of cocaine with particular emphasis enhancement of adrenergic activity leads to the accumulation of cytosolic calcium, and thereby increases the susceptibility to VF, will be tested. The effects of chronic cocaine use and acute withdrawal on the sensitivity to VF will also be investigated. The combination of exercise, acute ischemia and cocaine has been shown to induce VF reliably and will serve an a model of cocaine-induced VF. Pharmacologic interventions will be used to investigate adrenergic and intracellular contributions to VF. It is anticipated that once the mechanisms responsible for cocaine-induced VF have been determined, novel therapeutic interventions can be devised to reduce the number of these untimely deaths.

可卡因的普及和广泛使用已达到 流行比例。 伴随可卡因滥用的增加一直是 可卡因相关急诊室就诊的数量升级， 住院和死亡。 确实，有越来越多的证据表明 可卡因会引起致命的心血管事件，包括中风， 心肌梗塞和恶性心律疾病，例如 心室纤颤（VF）。 尽管在不断增长的关联 致命的心脏事件，对机制的了解相对较少 沉淀这些心血管事件，尤其是VF。 很好 确定可卡因可以增强肾上腺素能刺激的作用 反过来，已知可以降低心脏电稳定性。 这 增强肾上腺素活性有助于VF的机制不是 已知。 最终激活肾上腺素受体必须引起各种 心脏组织中的细胞反应。 这些改变 心脏细胞可能对VF的发展产生重大贡献。 它 因此，是提议的一系列实验的目的：a） 研究可卡因对心脏电稳定性的影响； b） 确定可卡因诱导的肾上腺素能活性增加的作用 玩VF； c）确定可卡因细胞内介体的作用 玩VF； d）研究可卡因的血液动力学作用 特别强调肾上腺素活性的增强导致 胞质钙的积累，从而增加易感性 将对VF进行测试。 慢性可卡因使用和急性的影响 还将研究对VF的敏感性的提款。 这 运动，急性缺血和可卡因的结合已显示为 可靠地诱导VF，并将为可卡因诱导的VF提供A模型。 药理干预措施将用于研究肾上腺素能和 对VF的细胞内贡献。 可以预见的是，一旦 已经确定了负责可卡因诱导的VF的机制 可以设计治疗干预措施以减少这些干预措施 不合时宜的死亡。