COCAINE-INDUCED VENTRICULAR FIBRILLATION

可卡因引起的心室颤动

• 批准号: 3212503
• 负责人: GEORGE Edward BILLMAN
• 金额: $ 13.25万
• 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/3212503
• 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.

可卡因的日益普及和广泛使用已达到 流行比例。 随着可卡因滥用的增加 与可卡因相关的急诊室就诊次数增加， 住院人数和死亡人数。 事实上，越来越多的证据表明 可卡因可引发致命的心血管事件，包括中风、 心肌梗塞和恶性心律失常，例如 心室颤动（VF）。 尽管之间的联系日益密切 致命的心脏事件，对其机制知之甚少 诱发这些心血管事件，特别是心室颤动。 很好 确定可卡因可以增强肾上腺素刺激的效果 反过来，已知这会降低心脏电稳定性。 这 肾上腺素能活性增强导致心室颤动的机制尚不明确 已知。 最终肾上腺素能受体的激活必须引起多种 心脏组织中的细胞反应。 这些改动在 心肌细胞对心室颤动的发生有显着贡献。 它 因此，拟议的一系列实验的目的是：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 在 VF 中播放； c) 确定可卡因细胞内介质的作用 在 VF 中播放； d) 研究可卡因对血液动力学的影响 特别强调肾上腺素能活性的增强导致 细胞质钙的积累，从而增加敏感性 到 VF，将进行测试。 长期使用可卡因和急性使用可卡因的影响 戒断对 VF 敏感性的影响也将被研究。 这 运动、急性缺血和可卡因的结合已被证明 可靠地诱发心室颤动，并将作为可卡因诱发心室颤动的模型。 药物干预将用于研究肾上腺素能和 细胞内对 VF 的贡献。 预计一旦 可卡因诱发室颤的机制已确定，新颖 可以设计治疗干预措施来减少这些疾病的数量 过早死亡。