Cardioprotective Effects Of Intracerebroventricular Morphine Preconditioning On Ischemia-reperfusion Injury In Intact Rat Heart

Objective Administration of morphine, opioid receptor(OR) agonist could mimic the cardioprotective effect of ischemic preconditioning (PC) in anesthetized open-chest rats. In this study, we want to investigate the protective effects of central nervous system morphine preconditioning on the myocardial ischemia/reperfusion injury of rat heart in vivo and its possible mechanism.Methods Thirty-six male Sprague-Dawley rats were randomly assigned into three groups after intracerebroventricular catheter placement, which include: control group(CON, n=6); ischemic preconditioning group(IPC, n=6);intravenous morphine preconditioning group(IV,1μg·kg-1,n=6); intracerebroventricular morphine preconditioning group(MPC, n=18). According to the dose of intracerebroventricular morphine, MPC group was further divided into three groups : MPC1,1μg·kg-1;MPC2,0.1μg·kg-1; and MPC3,0. 01μg·kg-1. Rats were either subjected to three cycles of 5 min of ischemia interspersed by 5 min of reperfusion followed by 30 min of reperfusion (ischemic preconditioning) or given intracerebroventricular morphine as three consecutive 5 min drug infusions interspersed by 5 min drug free period, followed by 30 min of normal myocardial perfusion (intracerebroventricular morphine preconditioning). All rats were subjected ischemic reperfusion injury process, which was induced by 30 min of left anterior descending artery occlusion followed by 2 hours of reperfusion. Indicators to be observed are composed of MAP,HR and RPP (MAP×HR); Infarct size, as a percentage of the area at risk, was determined by 2,3,5-triphenyltetrazolium staining, the volume of area at risk(AAR) and infarct size(IS), and the area of myocardial infarction, which is demonstrated by IS/AAR; And also the c-fos expression in the NTS was determined by immunohistochemical method. Meanwhile, the CGRP in the serum was tested by radioimmunity protocol.Results: Compared with control group, the volume of IS and IS/AAR both declined in group(P﹤0.05 and P﹤0.01); c-fos expressed in nucleus tractus solitarius (NTS) were lower than CON and IV group(P﹤0.01); the calcitonin-gene-related peptide (CGRP) in the serum were higher than CON and IV group(P﹤0.01). There is no significant statistical difference in other observed data among all groups.Conclusion: intracerebroventricular morphine preconditioning can mimic cardioprotective effect of IPC against ischemia-reperfusion injury, which may involve c-fos and CGRP.