The Delayed Myocardiol Protection Induced By ACEI And Its Interaction With ATP Sensitive Potassium Channel

Coronary artery disease and its sequelae-ischemia, myocardial infarction, and heart failure-are leading causes of morbidity and mortality in man. Considerable effort has been devoted toward improving functional recovery and reducing the extent of infarction after ischemic episodes. Murry et al. who showed that four 5-minute cycles of circumflex artery occlusion and reperfusion reduced infarct size produced by a long ischemia (40 minutes) in 1986. IPC (ischemia precondition) in the heart refers to the finding that brief periods of ischemia confer protection against infarction produced by a subsequent long ischemia. Experimental studies have demonstrated that the mechanism of ischemic preconditioning involves many endogenous myocardial protective substances, IPC as a therapy ischemic cardiomyopathy strategy is a hot field in recent years in medicine. The cardioprotect of IPC have two phase: classical preconditioning and delayed preconditioning. The acute protection (classical precondition) is preserved for 2 to 3 hours after the preconditioning period. The delayed preconditioning (second window of protection), occurring 20 to 24 hours after the preconditioning ischemia, and last to 72 hours. The cardioprotect of IPC include: improved myocytes cell survival decreased myocardial infraction size and against stunning improvement of functional recovery and antiarrhythmic Preservation of myocardial energy. Experimental studies have demonstrated that both classical precondition and delayed preconditioning involves many endogenous myocardial protective substances and a variety of intracellular signaling pathways. now the study on this mechanism focuse on "Trigger-media- effector". Trigger substance is the endogenous substance that released in episodes of sublethal ischemia. Adenosine bradykinin calcitonin-gene-related peptide (CGRP) adrenalin and so on is trigger substance which have effect through receptors. Experimental studies have demonstrated that receptors antagonist can abolish IPC's cardioprotect effect. Media is kinase. Endogenous myocardial protective substances agonists of G protein-coupled receptors lead to the activation of phospholipase C and the generation of phosphatidyl inositol bisphosphate (PIP2), and diacylglycerol (DAG). Diacylglycerol (DAG) can activation of phospholipase C. phospholipase C activates and translocate is key in IPC. PKC tagonist can mimic IPC's cardioprotect effect while PKC antagonist can abolish Tyrosine kinase-dependent signaling pathways is another signaling pathways. Effector" include: ion channeland cell protect protein ATP-sensitive-potassium-channel is widely prospected as common end-effector for signal transduction pathways. The advancement of precondition is from IPC to pharmacology precondition. IPC experiences the developing process of "ischemia precondition" to" the mechanism of ischemia precondition" to "pharmacology precondition." Angiotensin-converting-enzyme-inhibitior (ACEI) have a wider use in cardiovascular disease. recent study have demonstrated that which can antiarrhythmic decrease myocardial infraction size and against stunning effects. many researchers have been investigating into the protective effect and its mechanism of ACEI precondition because of its widely prospect of clinical useless. ACEI inhibits not only the production of angiotesionII, but also the degradation of the bradyknin. The bradyknin can increase the synthesize of NO and PGI2. Fosinopril is an ester pro-drug of the active Daicel fosinoprilat and is the first member of a new class of angiotension-converting enzyme inhibitors, the phosphoric acids. Fosinopril has a dual route of eliminating that is balanced between the liver and the kidneys. ATP-sensitive K+ (KATP) channels were found by Noma in 1983 in guinea pig -isolated ventricular myocytes by patch clamp. KATP channels is thought to produce vasorelaxation and myocardial protection against ischemia. Recent molecular biology and electrophysiological studies have provided useful information toward...