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Remote Preconditioning Induced By Skeletal Muscle Ischemia Protects Hearts Against Damage From Ischemia And Reperfusion

Posted on:2005-09-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:R Q XieFull Text:PDF
GTID:1104360125458245Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Myocardial ischemic preconditioning (IPC) is a phenomenon by which a brief episode(s) of myocardial ischemia increases the ability of the heart to a subsequent prolonged period of ischemic injury. This phenomenon and term was first described by Murry et al. Furthermore, remote preconditioning (RP) was described by which a brief episode(s) of renal or mesenteric ischemia can protect against damage during subsequent prolonged coronary occlusion (CAO) and reperfusion. More studies on mechanisms of IPC have been undertaken, but there is little understanding on RP. It is important to enhance the study on mechanism of RP so that the protection to heart induced by RP can be used fully. Recently, phenomenon of RP has been found in rats, dogs, pigs, as well as in human beings. It is possible that there are different mechanisms in different species or in different organs. Although some studies are understaking, little is known about the mechanism of RP on heart by skeletal muscle ischemia. In this study, we tried to explore the influence of RP induced by skeletal muscle ischemia on myocardial infarct size, apoptosis, endothelial dysfunction and changes of matrix metalloproteinases (MMPs) in a pig model of arteria femoralis occluding, and observed protective effects on hearts induced by skeletal muscle ischemia and Puerarin Glucose Injection in patients with CHD during PTCA.1 The roles of BK and opioid receptors in RP induced by skeletal muscle ischemia and their protective effects on infarct size and myocardial ultrastructure in pigsThe purpose of the study is to observe infarct size and myocardial ultrastructure by RP of skeletal muscle and role of BK and opioid receptors. Furthermore, index of ECG and IC-ECG is also studied. In the study, 48 pigs were divided into ten groups. The pigs in CONT group were subjected to 40min of left anterior descending coronary artery (LAD) occlusion followed by 120min reperfusion. The pigs in RP group were achieved by 15min of ischemia of arteria femoralis followed by 10min reperfusion before starting non-preconditioning control protocol. The role of BK and opioid receptors in remote cardiac preconditioning was investigated by using antagonist of the BK B2 receptors [Hoechst 140 (HOE-140)] or antagonist of the opioid receptors (naloxone). Anesthetized pigs were treated with HOE-140 or naloxone before starting the preconditioning protocol or non-preconditioned control protocol. Infarct size relative to ischemic area [radio of necrotic zone to ischemic zone (NZ/IZ)] was determined after 120min of reperfusion following 40min LAD occlusion. The results showed that NZ/IZ was less in the RP group compared with that in CONT group. NZ/IZ in CONT group was not affected by HOE-140 or naloxone. RP significantly protected the heart, which was prevented by HOE-140 or naloxone. After anesthetized pigs were treated with HOE-140 and naloxone simultaneously before starting the preconditioning protocol, the protective effect to the heart induced by RP was almost eliminated. Otherwise, pretreatment with hexamethonium could not abolish the protection induced by RP. Furthermore, BK infused into arteria femoralis continuously for 5min before starting non-preconditioned control protocol made NZ/IZ become less, which was not also abolished by hexamethonium.Results of ultrastructure of myocardium and changes of indexes of ECG and IC-ECG showed similar corresponding patterns.The data showed that RP induced by skeletal muscle could protect heart by reducing the infarct area and protecting ultrastructure, in which BK and opioid receptors might trigger the protective effect. Furthermore, the protective effect might be added up by activating BK B2 receptors and opioid receptors. And the protection could not be abolished by hexamethonium.2 Effect on apoptosis of myocardium by RP induced by skeletal muscle and roles of BK and opioid receptors on it in pigsIschemia and reperfusion (I/R) can not only induce lethal cells injury but also induce apoptosis in myocardium. Although both apoptosis an...
Keywords/Search Tags:RP, skeletal muscle, heart protection, BK, opioid receptors
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