ETHANOL AND CARDIOPROTECTION FROM ISCHEMIA--NMR STUDIES

乙醇和对缺血的心脏保护作用——核磁共振研究

• 批准号: 6088379
• 负责人: MARTIN M PIKE
• 金额: $ 7.18万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6088379
• 关键词: alcoholic beverage consumption; atomic absorption spectrometry; calcium flux; chemoprevention; ethanol; guinea pigs; myocardial ischemia /hypoxia; nuclear magnetic resonance spectroscopy; potassium channel; reperfusion

Recent studies have indicated that moderate ethanol consumption induces a chronic state of cardio-protection which results in reduced ischemia/reperfusion injury. The mechanisms for this protection are largely unknown but may overlap with those induced by ischemic preconditioning. The understanding of the mechanisms by which ethanol induces a stable state of cardioprotection are of great interest in regards to the eventual implementation of such protection in the clinical arena. The final effector mechanisms for the cardioprotection induced by either ischemic preconditioning or ethanol consumption are poorly understood. Little data is available in the ethanol protected heart, which address metabolic variables involved with ischemic injury, and how they may be altered. Guinea pigs will be given 10 percent ethanol for a period of 6 weeks, and compared to age matched controls. Hearts will be isolated and Langendorff perfused; function will be measured by left ventricular balloon. Specific Aim I is to investigate the cationic and energetic effects of regular ethanol consumption during subsequent myocardial ischemia/reperfusion, in order to evaluate the involvement of such effects in the concomitant improvement of postischemic function in the ethanol protected heart. Intracellular Na+, pH and high energy phosphates will be assessed during ischemia/reperfusion in the perfused guinea pig heart using interleaved 23Na+ and 31P NMR spectroscopy. 19F NMR spectroscopy and atomic absorption techniques will be used to measure changes in cytosolic free Ca2+ and tissue Ca2+, respectively. Lactate dehydrogenase release will be measured. These experiments will test the hypothesis that the functional improvement (and decreased cell death) observed with regular moderate alcohol consumption is associated with an altered pattern of energetic depletion and cation overload during ischemia and/or reperfusion In addition, the project will investigate the role of the ATP dependent K+ (KATP) channel in ethanol-induced cardioprotection. This KATP channel which is normally only activated under ischemic conditions, has been shown to play a clinical role in cardioprotection arising from ischemic preconditioning. It's role in ethanol induced preconditioning is unknown. Specific Aim 2 is to test the hypothesis that KATP channel activation is required for the improvement of postischemic function in ethanol protected myocardium, as well as the associated alterations in the cationic and energetic state during ischemia and/or reperfusion. This will be accomplished by administration of a specific KATP channel inhibitor, 5-hydroxydecanoate.

最近的研究表明，适度的乙醇消费会导致 慢性心脏保护状态，导致降低 缺血/再灌注损伤 这种保护机制主要是 未知，但可能与缺血预处理诱导的那些重叠。的 了解乙醇诱导稳定状态的机制， 心脏保护对于最终的 在临床竞技场实施这种保护。 最终的效应 缺血预处理诱导的心肌保护机制 或乙醇的消耗量知之甚少。数据很少， 乙醇保护心脏，这解决了代谢变量， 缺血性损伤，以及它们如何被改变。豚鼠将被给予10 %乙醇持续6周，并与年龄匹配的 对照心脏将被隔离，Langendorff灌注;功能将被检查。 通过左心室球囊测量。具体目标I是调查 定期饮用乙醇的阳离子和能量效应 随后的心肌缺血/再灌注，以评估 这些作用参与缺血后的伴随改善， 在乙醇保护的心脏中发挥作用。细胞内Na+、pH和高能 将在灌注的豚鼠的缺血/再灌注期间评估磷酸盐 猪心脏使用交错的23 Na+和31 P NMR光谱。19F NMR 光谱和原子吸收技术将被用来测量变化 胞浆游离Ca ~（2+）和组织Ca ~（2+）。乳酸脱氢酶 释放将被衡量。这些实验将检验这一假设， 常规治疗观察到的功能改善（和细胞死亡减少） 适度饮酒与改变的 缺血和/或再灌注期间的能量消耗和阳离子超负荷 此外，该项目还将研究ATP依赖性K+的作用， （KATP）通道在乙醇诱导的心脏保护中的作用。这个KATP通道 通常只在缺血条件下激活，已被证明发挥作用， 在缺血预处理引起的心脏保护中的临床作用。这是 在乙醇诱导的预处理中的作用尚不清楚。具体目标2是测试 假设KATP通道激活是改善 乙醇保护心肌的缺血后功能，以及 缺血期间阳离子和能量状态的相关改变 和/或再灌注。这将通过管理一个特定的 KATP通道抑制剂，5-羟基癸酸。