MITOCHONDRIAL DNA DELETIONS IN CARDIAC SURGERY

描述：(改编自调查人员摘要)现在是一部作品 表明线粒体DNA缺陷可能是通过 遗传或后天途径与心血管疾病相关 异常现象。此前，研究人员已经证明线粒体 钙([Ca]mt)积累和线粒体基因表达 在外科手术诱导的全脑缺血和再灌流过程中发生改变 这些改变与缺血后功能下降有关 老有所养，心不成熟。他们还表明， 老年心脏内[Ca~(2+)]-MT积聚增加与 线粒体基因表达和酶活性降低。这些 研究表明，这些现象与保存率下降和 大鼠脑缺血再灌流过程中高能磷酸盐的再合成 陈旧性心肌。在使用一部小说进行初步调查时 聚合酶链式反应方法学，PI显示在兔 心脏mtDNA7,436缺失的患病率在 全脑缺血和再灌流，这些改变与 老年POT缺血区功能恢复下降，但不是 成熟的心。在一项平行的研究中，使用了来自 接受心脏手术的人类患者也得到了类似的结果 结果表明，缺血-再灌注增加了高血压的发病率。 线粒体DNA，436缺失。导致这些变化的病理生理学 线粒体DNA及其与心肌功能障碍的关系仍有待进一步研究 然而，初步调查表明，AT-RICH 兔和人心脏mtDNA7,436缺失侧翼序列 可能是有意义的。调查人员计划调查 线粒体DNA缺失在临床相关动物模型中的相关性 心脏手术患者的人心房组织样本测定 导致线粒体DNA缺失患病率增加的机制 并确定缺血和/或再灌注的身份和亲缘关系 线粒体DNA缺失在脑缺血后功能恢复中的作用 心脏手术病人。这些研究将提供关于以下方面的见解： 线粒体DNA缺失在心脏病患者中的发生率； 心肌老化；以及线粒体DNA缺失对手术结果的影响。 此外，这些调查将提供信息，以便 用于开发替代的心肌保护外科手术程序 优化心脏手术患者的潜在结局。

DESCRIPTION: (Adapted from investigator's abstract) A body of work now exists to suggest that mitochondrial DNA defects occurring either through inherited or acquired pathways are associated with cardiovascular abnormalities. Previously, the investigator have shown that mitochondrial calcium ([Ca2+]mt) accumulation and mitochondrial gene expression are altered during surgically induced global ischemia and reperfusion and that these alterations are associated with decreased post-ischemic functional recovery in the aged but not the mature heart. They have also shown that increased [Ca2+]mt accumulation in the aged heart was associated with decreased mitochondrial gene expression and enzyme activity. These phenomena were shown to be related to decreased preservation and resynthesis of high energy phosphates during ischemia and reperfusion in the aged myocardium. In preliminary investigations using a novel polymerase chain reaction methodology, the PI showed that in the rabbit heart the prevalence of the mtDNA7, 436 deletion is increased during global ischemia and reperfusion and that these alterations are associated with decreased pot ischemic functional recovery in the aged but not the mature heart. In a parallel study using atrial appendage tissues from human patients undergoing cardiac surgery, similar results have been obtained indicated that ischemia-reperfusion increases the prevalence of the mtDNA, 436 deletion. The pathophysiology leading to these alterations in mtDNA and their relationship to myocardial dysfunction remain to be elucidated, however, preliminary investigation would suggest that AT-rich sequences flanking the mtDNA7,436 deletions in the rabbit and human heart may be of significance. The investigators plan to investigate the relevance of mtDNA deletions in a clinically relevant animal model and in human atrial tissue samples from cardiac surgery patients to determine the mechanisms leading to increased prevalence of mtDNA deletions during ischemia and/or reperfusion and to determine the identity and relative contribution of mtDNA deletions to post-ischemia functional recovery in the cardiac surgical patient. These studies will provide insight as to: the prevalence of mtDNA deletions in the cardiac patient; the effect of myocardial aging; and the effect of mtDNA deletions on surgical outcome. In addition, these investigation will provide information which will allow for the development of alternative myoprotective surgical procedures to optimize potential outcome in cardiac surgical patients.