Sustained Coronary Stenosis and Hibernating Myocardium

持续冠状动脉狭窄和冬眠心肌

• 批准号: 6723772
• 负责人: RAYMOND K KUDEJ
• 金额: $ 12.41万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6723772
• 关键词: artery stenosis; blood flow measurement; calcium flux; heart circulation; hibernation; marmots; myocardium; nitric oxide; swine

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.

描述（改编自申请人摘要）：该候选人 Kudej博士已经完成了小动物外科住院医师和博士学位 在生物医学工程计划，并接受了博士后培训， 哈佛医学院的心血管生理学。 他的目标是进一步 确立了自己作为心血管研究人员的地位，并获得了额外的 基本的科学研究工具，使他能够开发一个独立的R 01 建议并建立一个成功和有益的心血管事业 research. 目前的建议首先旨在审查负责的机制 用于维持存在于两种模型中的心肌血流， 冬眠心肌：慢性冠状动脉狭窄猪模型， 显示了人类冬眠心肌的许多特征， 在土拨鼠真正的冬眠期间（M。monax）。 第二，机制 控制这两种模型中局部心肌功能的改变 将被审查。 具体而言，该提案的两个假设是：A） 冠状动脉血流在冬眠心肌中得以维持，这可能是由于 NO的上调;和B）收缩和舒张的适应性改变 左心室功能存在于冠状动脉缩窄部远端 在猪和冬眠的土拨鼠中， 钙处理机制的改变。 需要获取的信息 将直接应用于患有冠状动脉的人 慢性冠状动脉狭窄。 此外，了解基本的 增强心肌组织性能的潜在机制， 冬眠的哺乳动物可以提供对人类病理学的见解。 1999年7月， PSUCM将建立一个整合分子医学系， 遗传学，将由斯蒂芬瓦特纳，医学博士，一个著名的研究人员， 是从哈佛大学招募来的 瓦特纳博士的调查小组 迅速发展，加入该部门的教师将发挥作用， 在培训Kudej博士方面发挥了重要作用。 该部门得到了很好的支持 外部的 NIH对研究所教师的资助包括一个项目 奖，一个优秀奖，和几个R 01，R29和国家研究服务 奖