Contractile Force in Human Heart Failure

人类心力衰竭的收缩力

• 批准号: 6538023
• 负责人: EIAS JWEIED
• 金额: $ 5.01万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6538023
• 关键词: calcium channel; cardiac myocytes; heart contraction; heart failure; human tissue; laboratory rat; microfilaments; muscle tension; phosphorylation; postdoctoral investigator; receptor sensitivity

DESCRIPTION (the applicant?s description verbatim): The decline in pump function characteristic of human heart failure has at its basis a depression of myocyte function. The underlying cellular mechanisms are unknown. A problem with trying to demonstrate decreased myofilament Ca2+ sensitivity and tension development in human heart failure is that human donor heart tissue, which is used as the control in skinned cardiocyte measurements of contractile force, has usually undergone tremendous adrenergic stimulation prior to organ harvest. This may explain why in previous studies on human tissue it has been the CHF cardiocytes that has had greater calcium sensitivity and tension development than donor cardiocytes. We hypothesize that donor human myocardium is extensively phosphorylated at the time of organ harvest. We also hypothesize that in end-stage human heart failure, there is a decrease in calcium sensitivity and tension development. We hypothesize distinctions may also exist in the degree of this dysfunction when comparing idiopathic dilated cardiomyopathy vs. ischemic cardiomyopathy. We have two specific aims: Aim 1) Assess myofilament calcium sensitivity of human donor cardiocytes before and after dephosphorylation. Aim 2) Assess myofilament calcium sensitivity of human cardiocytes of ischemic and idiopathic heart failure tissue and compare results between these groups. First, we propose to apply a technique of dephosphorylating human donor cardiocytes. Trials will first be conducted in rat myocardium, which is more abundant, to duplicate the success already achieved in other laboratories and to standardize results in our own laboratory. Second, we will conduct similar experiments in human CHF cardiocytes. Significance: Detailed knowledge regarding the molecular mechanisms of human heart failure will promote the development of novel treatment strategies aimed to combat this lethal disease.

描述（申请人？）如：(1)泵的下降