MYOCARDIAL ENERGY METABOLISM-EFFECT OF ETHANOL

该项目的长期目标是建立 乙醇引起的心肌能量改变与 代谢和乙醇相关的心肌退行性变化。 一个 目前的目标是建立大鼠作为动物模型， 酒精引起的心脏病 大鼠将被喂食乙醇饮食， 脂肪和卡路里含量。 这些饮食的功效， 酒精引起的心脏病的发病率将会上升。 标准 病理学包括线粒体和肌浆网变形， 电镜观察肌原纤维变性。 在 除了超微结构研究外，还将对组织进行分析， 腺嘌呤核苷酸、肌酸和磷酸肌酸浓度， 评估其能量状态。 将测定分离的线粒体的 催化氧化磷酸化的能力。 这些最初的测量 将作出，以遵循乙醇相关的进展， 不同膳食条件下心肌能量代谢的变化 养生法 在建立含乙醇的饮食后， 肌原纤维的退行性变化，将进行研究以评估 乙醇进料影响与胃相关的 氧化磷酸化系统。 此前发表的研究表明， 心脏线粒体合成ATP的能力会被 乙醇消费 实验的目的是找出 酒精相关的病变，限制率和/或 ATP合成的程度。 上述研究将把早期变化与 心脏能量代谢和形态学改变， 乙醇消费。 对这些早期变化的仔细描述 与乙醛消耗量的关系应该表明分子转化 最终导致永久性心脏损伤， 长期酗酒者 因此，这些研究对于阐明 酒精性心脏病的发病机制。

The long-range objective of this project will be to establish the relationship between ethanol-elicited alterations in myocardial energy metabolism and ethanol-related degenerative changes in the myocardium. An immediate objective is to establish the rat as an animal model for alcohol-induced cardiac disease. Rats will be fed ethanol diets which vary in their lipid and caloric content. The efficacy of these diets to give rise to alcohol-induced cardiac disease will be established. Criteria for pathology include distortion of mitochondria and sarcoplasmic reticulum, and degeneration of myofibrils as detected by electron microscopy. In addition to the ultrastructure studies, the tissue will be analyzed for adenine nucleotide, creatine, and creatine phosphate concentrations to evaluate its energy state. Isolated mitochondria will be assayed for their ability to catalyze oxidative phosphorylation. These initial measurements will be made in order to follow the progression of ethanol-related alterations in myocardial energy metabolism under different dietary regimens. Upon establishing an ethanol-containing diet that gives rise to degenerative changes in myofibrils, studies will be carried out to assess the degree to which ethanol feeding affects the mitochondrial-associated oxidative phosphorylation system. Previously published studies indicate that the ability of cardiac mitochondria to synthesize ATP is diminished by ethanol consumption. Experiments are designed to pinpoint those ethanol-related lesions in the mitochondrion that limit the rate and/or the extent of ATP synthesis. The above studies will correlate early changes in cardiac energy metabolism and morphological alterations which are related to ethanol consumption. A careful characterization of these early changes related to ethanal consumption should suggest molecular transformations which ultimately lead to the permanent cardiac damage observed in many chronic alcoholics. These studies thus are important in elucidating the pathogenesis of alcohol-induced cardiac disease.