PILOT--EFFECT OF ALCOHOL AND SEPSIS ON CARDIAC RATE

试点——酒精和脓毒症对心率的影响

• 批准号: 3745404
• 负责人: KATHLEEN H MC DONOUGH
• 金额: --
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3745404
• 关键词: arrhythmia; blood glucose; blood lipid; blood pressure; electrocardiography; endotoxins; ethanol; heart metabolism; heart rate; high performance liquid chromatography; isoproterenol; myocardial ischemia /hypoxia; peroxidation; physiologic stressor; reperfusion

Chronic alcohol consumption has been shown to induce a cardiomyopathy which appears to be directly correlated with the duration and quantity of alcohol that is consumed. Along with changes in cardiac mechanical function and morphology, there also appear to be changes in the cardiac conduction system. However, before overt changes in myocardial contraction, morphology or conduction have been manifested, alterations may have already occurred that make the myocardium more susceptible to injury by a second stress. Ischemia and reperfusion of the myocardium is a stress to the heart that results in many cardiac deaths not only because of mechanical damage to the heart but also because cardiac arrhythmias are a major consequence of both the ischemic insult and the reperfusion condition. The hypotheses to be tested in this pilot proposal are that ischemic insult and the potentiates arrhythmias induced either by ischemia and reperfusion or by isoproterenol administration mild oxidant stress seems to initiate the development of protective mechanisms in the myocardium that may produce better tolerance to a second oxidant stress. For example, pretreatment of an animal with a mild dose of endotoxin 24 hrs prior to an ischemia/reperfusion insult results in better recovery of ventricular function of the endotoxin treated than of the control treated groups. Thus, we propose in this pilot study to determine the effects of chronic alcohol consumption (8-10 weeks), with alcohol as 36% of the caloric intake, on the severity of arrhythmias induced by ischemia by ischemia and reperfusion or by high doses of isoproterenol. In other groups of animals the effects of the acute administration of alcohol, to achieve blood levels of approximately 200 mg/dl, on ischemia and reperfusion induced arrhythmias or isoproterenol induced arrhythmias will be determined. Finally, the possible attenuation of ischemia/reperfusion and isoproterenol induced arrhythmias by 24 hour pretreatment with endotoxin will be assessed. Al of these studies will be performed in vivo, in anesthetized rats in which blood pressure, heart rate and the electrocardiogram will be monitored continuously. The severity of the arrhythmic changes will be quantitated by determining initial changes in ventricular rhythm, ventricular tachycardia and finally ventricular fibrillation. Both time to initiation of rhythm disturbances and duration of rhythm disturbances will be quantitated to achieved an arrhythmia severity index as reported by other investigators studying arrhythmogenicity.

慢性饮酒已被证明会诱导心肌病 似乎与持续时间和数量直接相关 消耗的酒精。 随着心脏机械的变化 功能和形态，心脏似乎也发生了变化 传导系统。 但是，在明显变化心肌之前 收缩，形态或传导已经表现出来，改变 可能已经发生了使心肌更容易受到的 第二个压力受伤。 心肌的缺血和再灌注 是对心脏的压力，导致许多心脏死亡不仅 由于对心脏的机械损害，但也因为心脏 心律不齐是缺血性侮辱和 再灌注条件。 该飞行员要测试的假设 建议是缺血性侮辱和增强心律不齐 通过缺血和再灌注或异丙肾上腺素给药 轻度氧化剂应力似乎启动了保护性的发展 心肌中的机制可能会产生更好的耐受性 第二氧化应激。 例如，对动物的预处理 缺血/再灌注之前，温和剂量的内毒素24小时 导致内毒素的心室功能更好地恢复 比对控制治疗组的治疗。 因此，我们建议 试点研究确定慢性酒精消耗的影响（8-10 几周），酒精是热量摄入量的36％，严重程度 缺血和再灌注引起的缺血诱导的心律失常或高 异丙肾上腺素的剂量。 在其他动物中 急性施用酒精，以达到大约的血液水平 200 mg/dl，缺血和再灌注引起心律不齐或 将确定异丙肾上腺素诱导的心律不齐。 最后， 缺血/再灌注和异丙肾上腺素的可能衰减 将评估心律不齐24小时预处理，并评估内毒素。 al 在这些研究中，将在体内进行麻醉大鼠 血压，心率和心电图将受到监测 连续。 心律失常变化的严重程度将被定量 通过确定心室心律的初始变化，心室 心动过速，最后是心室纤颤。 这两个时间 节奏扰动和节奏障碍的持续时间的启动 如报道 其他研究人员研究心律失常。