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: 3726092
• 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/3726092
• 关键词: arrhythmia; blood glucose; blood lipid; blood pressure; blood toxicology; 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.

长期饮酒已被证明会诱发心肌病 这似乎与持续时间和数量直接相关 所消耗的酒精量。 随着心脏机械的变化 功能和形态，心脏也似乎发生了变化 传导系统。 然而，在心肌发生明显变化之前 收缩、形态或传导已显现、改变 可能已经发生，使心肌更容易受到 第二次压力造成的伤害。 心肌缺血和再灌注 是对心脏的压力，不仅导致许多心脏死亡 因为心脏的机械损伤，也因为心脏 心律失常是缺血性损伤和心律失常的主要后果 再灌注情况。 本试点项目要测试的假设 建议是缺血性损伤和增强诱发的心律失常 通过缺血和再灌注或异丙肾上腺素给药 温和的氧化应激似乎会引发保护性的发展 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，用 缺血/再灌注损伤前 24 小时给予轻度剂量的内毒素 使内毒素的心室功能更好地恢复 治疗组的治疗效果优于对照组。 因此，我们在此建议 确定长期饮酒影响的试点研究（8-10 周），酒精占热量摄入的 36%，对严重程度的影响 由缺血和再灌注或高浓度缺血引起的心律失常 异丙肾上腺素的剂量。 在其他动物群体中的影响 急性饮酒，使血液浓度达到大约 200 mg/dl，用于缺血和再灌注引起的心律失常或 异丙肾上腺素引起的心律失常将被确定。 最后， 可能减弱缺血/再灌注和异丙肾上腺素诱导的作用 将评估内毒素预处理 24 小时的心律失常。 铝 其中一些研究将在麻醉大鼠体内进行 将监测血压、心率和心电图 连续地。 心律失常变化的严重程度将被量化 通过确定心室节律的初始变化，心室 心动过速，最后出现心室颤动。 两次时间都到 节律紊乱的开始和节律紊乱的持续时间 将进行定量以达到报告的心律失常严重程度指数 由其他研究心律失常性的研究人员进行。