COCAINE-INDUCED VENTRICULAR FIBRILLATION

可卡因的日益普及和广泛使用已经达到 流行病的比例。 可卡因滥用增加的同时， 与可卡因有关的急诊室就诊次数的增加， 住院和死亡。 事实上，越来越多的证据表明， 可卡因可以引起致命的心血管事件，包括中风， 心肌梗死和恶性心律失常， 心室颤动（VF）。 尽管越来越多的人 致命的心脏事件，相对而言，对机制知之甚少 诱发这些心血管事件，特别是VF。 公 证实可卡因可以增强肾上腺素能刺激的效果 这又已知会降低心脏电稳定性。 的 增强的肾上腺素能活性导致VF的机制不是 知道的 肾上腺素能受体的最终激活必须引起各种 心脏组织的细胞反应。 这些变化在 心肌细胞可能对VF的发展有重要作用。 它 因此，拟议的一系列实验的目的是： 研究可卡因对心脏电稳定性的影响; B） 确定可卡因引起的肾上腺素能活动增加的作用 c）确定可卡因的细胞内介质在VF中的作用， 在VF中发挥作用;以及d）研究可卡因与 特别强调肾上腺素能活性的增强导致 细胞质钙的积累，从而增加易感性 到VF，将进行测试。 长期使用可卡因和急性使用可卡因 还将研究停药对VF敏感性的影响。 的 运动，急性缺血和可卡因的组合已经被证明， 可靠地诱发VF，并将作为可卡因诱发VF模型。 药理学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 已确定可卡因诱导VF的机制， 可以设计治疗性干预措施来减少这些 不合时宜的死亡

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.