权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Small heat shock proteins in surgically-induced myocardial stunning

手术引起的心肌顿抑中的小热休克蛋白

基本信息

批准号：
8282860
负责人：
Richard T Clements
金额：
$ 24.9万
依托单位：
RHODE ISLAND HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8282860
关键词：
Acidosis Binding Binding Proteins Biological Preservation Blood Cardiac Cardiac Myocytes Cardiac Surgery procedures Cardiopulmonary Bypass Catheters Coronary Artery Bypass Crystallins Data Disease Drug Delivery Systems Gene Delivery Genetic Heart Heart Arrest Heat Shock Protein 27 Heat shock proteins Hour Hypoxia Impairment Induced Heart Arrest Injury Intervention Ischemia Literature Location Low Cardiac Output Syndrome Mediating Metabolic Muscle Cells Myocardial Myocardial Stunning Myocardium Operative Surgical Procedures Oxidants Patients Pattern Phosphorylation Phosphorylation Inhibition Phosphotransferases Play Prophylactic treatment Proteins Rattus Research Design Risk Role Signal Transduction Solutions Staining method Stains Testing Therapeutic Intervention Time Tissues Treatment Protocols base design gene therapy heart cell improved mortality mutant natural hypothermia overexpression repaired response treatment strategy

项目摘要

The majority of coronary artery bypass grafting (CABG) and valve repair surgeries use cardioplegia and cardiopulmonary bypass (CP/CPB) to respectively arrest the heart and systemically circulate oxygenated blood. Hypothermic cardioplegia solutions provide myocardial protection during prolonged surgicallyinduced global ischemia that would otherwise prove lethal. However, cardioplegic arrest of the heart during surgery results in reversible ischemic injury that manifests in impaired contractility of viable myocardium and reductions in cardiac function (a.k.a myocardial stunning). In the majority of patients, this temporary impairment resolves quickly, however ~ 10 % can develop an associated cardiac low output syndrome lasting hours to days that greatly enhances the risk of mortality. Following CP/CPB, HSP27 and cryAB are phosphorylated on multiple residues. Current data in the literature suggests that the presence of nonphosphorylated sHSP is beneficial for post ischemic contractile function, and that ischemic insults (including CP/CPB) that induce phosphorylation of HSP27 and cryAB, and subsequent depletion of the nonphosphorylated sHSP pool, may play a role in myocardial contractile deficits or stunning. These studies are designed around the central hypothesis that preservation of non-phosphorylated HSP27 and cryAB levels will reduce or block CP-induced deficits in myocardial contractility. These studies will be performed in Aim I - Determine the upstream signaling mechanism of CP/CPB-induced HSP27 and cryAB phosphorylation. Aim II - Determine if overexpression of phospho-mutant sHSP's will reduce cardioplegia-induced contractile deficits in isolated myocytes. Aim III - Determine specific cardiac contractile signaling mechanisms associated with ischemia-induced alterations in sHSP proteins. Experimental interventions (pharmacological and genetic approaches) will be performed using isolated rat cardiomyocytes and Langendorff perfused hearts. If these Aims are successful, these studies will enhance our understanding of CP-induced contractile deficits, and suggest treatment strategies that could greatly improve current myocardial protection and reduce complications associated with cardiac surgery

大多数冠状动脉旁路移植术（CABG）和瓣膜修复手术采用心脏截流术