Sustained Coronary Stenosis and Hibernating Myocardium

描述(改编自申请人的摘要)：应聘者 提案，库德杰博士已经完成了小动物外科住院医师和博士学位 生物医学工程计划，并在 哈佛医学院心血管生理学。他的目标是进一步 确立自己作为心血管研究人员的地位并获得更多 基础科学研究工具，允许他开发独立的R01 建议并建立一个成功和有益的心血管职业生涯 研究。 目前的提案首先是为了审查负责的机制 用于维持两种模型的心肌血流量 冬眠心肌：一种慢性冠状动脉狭窄的猪模型 展示了人类冬眠心肌的许多特征，以及 在土拨鼠(M.monax)真正冬眠期间。第二，机制 控制这两种模型局部心肌功能的变化 将会被检查。具体地说，该提案的两个假设是：a) 在冬眠的心肌中维持冠脉血流，可能是由于 上调NO；以及B)收缩和舒张期的适应性改变 左心功能存在于非晶状体冠脉缩窄远端 在猪和冬眠的土拨鼠中，心脏与协调的 钙处理机制的改进。要获取的信息 这项建议将直接适用于患有冠状动脉的人类 疾病和慢性冠状动脉狭窄。此外，了解基本的 心肌组织功能增强的机制 冬眠的哺乳动物可能会提供对人类病理的洞察。1999年7月， PSUCM将设立综合分子医学系和 遗传学，由斯蒂芬·瓦特纳医学博士负责，他是一位著名的研究人员， 是从哈佛大学招聘的。瓦特纳博士的调查小组已经 迅速成长，加入系的教职员工将扮演一个 在培训库德杰博士方面发挥了重要作用。该部门得到了很好的支持 从外部来说。NIH为研究所教职员工提供的资金包括一个项目项目 奖，一个功勋奖，几个R01，R29和国家研究服务 奖项。

DESCRIPTION (Adapted from the applicant's abstract): The candidate for this proposal, Dr. Kudej, has completed a small animal surgery residency and PhD program in biomedical engineering and received his postdoctoral training in cardiovascular physiology at Harvard Medical School. His goal is to further establish himself as a cardiovascular researcher and to acquire additional basic science research tools to allow him to develop an independent R01 proposal and build a successful and rewarding career in cardiovascular research. The current proposal is designed first to examine the mechanisms responsible for the maintenance of myocardial blood flow present in two models of hibernating myocardium: a swine model of chronic coronary constriction, which demonstrates many characteristics of hibernating myocardium in humans, and during true hibernation in the woodchuck (M. monax). Second, the mechanisms governing the alterations in regional myocardial function in these two models will be examined. Specifically, the two hypotheses of this proposal are: A) Coronary blood flow is maintained in hibernating myocardium, potentially due to up-regulation of NO; and B) Adaptive alterations in systolic and diastolic left ventricular function present distal to the ameroid coronary constrictor in swine and in hibernating woodchuck hearts are associated with a coordinated modification of calcium handling mechanisms. The information to be acquired from this proposal will be directly applicable to humans with coronary artery disease and chronic coronary stenosis. Additionally, understanding the basic mechanisms underlying the enhanced performance of myocardial tissue from hibernating mammals may provide insights into human pathology. In July 1999, the PSUCM will established a Department of Integrative Molecular Medicine and Genetics, to be overseen by Stephen Vatner, MD, a well-known researcher who was recruited from Harvard University. Dr. Vatner's investigative team has grown rapidly and faculty who have joined the department will play an important role in training Dr. Kudej. The department is well supported externally. NIH funding for institute faculty includes one program project award, one merit award, and several R01s, R29s, and National Research Service Awards.