ETHANOL AND CARDIOPROTECTION FROM ISCHEMIA--NMR STUDIES

最近的研究表明，适度的乙醇消费会导致 心脏保护的慢性状态，导致心脏保护减少 缺血/再灌注损伤。这种保护的机制主要是 未知，但可能与缺血预适应诱导的结果重叠。这个 了解乙醇诱导细胞的稳定状态的机制 心脏保护对于最终的 在临床领域实施这种保护。最终效应器 任一种缺血预适应诱导心肌保护的机制 或者，人们对乙醇的消费知之甚少。中提供的数据很少。 乙醇保护的心脏，它解决了与 缺血性损伤，以及它们可能如何改变。豚鼠将被给予10只 6周，并与年龄匹配的人进行比较 控制。心脏将被隔离，朗多夫将被灌流；功能将被 用左心室气囊测量。我的具体目标是调查 正常饮酒过程中的阳离子和能量效应 随后的心肌缺血/再灌流，以评估 这种效应参与了脑缺血后的伴随改善 在乙醇保护的心脏中起作用。细胞内钠、pH与高能 在灌流的豚鼠中，将评估磷酸盐在缺血/再灌注期间的作用 用交错的~(23)Na和~(31)P核磁共振波谱研究猪心。~(19)F核磁共振 光谱和原子吸收技术将被用来测量变化 细胞内游离钙和组织钙分别为。乳酸脱氢酶 将测量释放量。这些实验将检验这样一个假设，即 在常规治疗中观察到功能改善(和减少细胞死亡) 适量饮酒与一种改变的 缺血和/或再灌流时的能量耗竭和阳离子超负荷 此外，该项目还将调查依赖于ATP的K (KATP)通道在乙醇诱导的心肌保护中的作用。这个KATP频道是 正常情况下只在缺血条件下激活，已被证明发挥了 缺血预适应在心脏保护中的临床作用。它是 在乙醇诱导的预适应中的作用尚不清楚。具体目标2是测试 假设KATP通道激活是改善心力衰竭所必需的 乙醇保护心肌的缺血后功能 脑缺血时阳离子和能量状态的相关变化 和/或再灌流。这将通过管理特定的 KATP通道抑制剂，5-羟基癸酸。

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.