Effects Of Cardiac Sensory Nerves On Cardioprotection Of Postconditioning And Related Mechanisms Study

Background:With the popularization and application of the technology of the heartduring cardiopulmonary bypass,coronary artery bypass graft,percutaneous coronaryintervention, myocardial ischemia-reperfusion has become a commonpathophysiological change, meanwhile which become the challenge ofcardiovascular surgery. In2003,with the concept of IpostC Ischemiapostconditioning has been proposing, making the cardioprotection of IpostC and therelated mechanism to be a research hotspot. CGRP calcitonin gene-related peptide and SP substance P are important neuropeptides of the sensory nerve fibers, whichinvolving in the regulation of the life activities. The existing research shows thatCGRP and SP involved in the regulation of the cardiovascular system, little is knownabout the role of them on the the regulatory effects and the mechanism of IpostC. Sowe established the current study to investigate whether the sensory nerve and itsneurotransmitters （CGRP and SP） are involved in the protective effect of IpostCwhich further explore the neurogenic mechanism of IpostC in rats.Object we established the current study to determine:1. whether ischemic-postconditioning applied at the beginning of reperfusion couldup-regulated the expression of CGRP and SP;2. To evaluate whether endogenous CGRP and SP are involved in the cardioprotectionof ischemic-postconditioning, including cardiac hemodynamics, ventriculararrhythmias and myocardial infarct size after reperfusion, which further explore theneurogenic mechanism of the organ injury in rats. Method: Making the model of acute myocardial ischemia-reperfusion andischemia-postconditioning with the healthy male SD rats, the experiment has beendivided into four parts:1. The eluates were processed using ELISA enzyme linked immunosorbent assay for measurement of SP, CGRP concentrations in myocardium and serum at ischemicreperfusion15min and2.5H after IpostC.2. Observed pretreatment with CGRP_8-37（10-6mol L-1,10-7mol L-1）, RP6758010^-510^-6mol·L^-1) or joint application CGRP8-37（10-6mol L-1） and RP67580（10-6mol L-1）, the change of myocardial infarct size of reperfusion after IpostC.3. Observed pretreatment with CGRP_8-37（10-6mol L-1,10-7mol L-1）, RP6758010^-5,10^-6mol·L^-1 or joint application CGRP_8-37（10-6mol L-1） and RP67580（10-6mol L-1）, the change of hemodynamic of reperfusion after IpostC.4. Observed pretreatment with CGRP_8-37（10-6mol L-1,10-7mol L-1）, RP6758010-5è10-6mol·L-1or joint application CGRP_8-37（10-6mol L-1） and RP67580（10-6mol L-1）, the change of ventricular arrhythmia of reperfusion after IpostC.Result:1.The change of concentration of CGRP and SP in myocardium and serum at differenttime of ischemic reperfusion after IpostC:Compared with group IR èthe concentrations of CGRP and SP in myocardiumand serum were significantly up-regulated at ischemic reperfusion15min and2.5Hafter IpostC.2. The effection of CGRP and SP to myocardial infarct size of reperfusion afterIpostC:Compared with group IR èthe myocardial infarct size（IS/AAR%） wassignificantly decreased in group IpostC. Compared with group IpostC, pretreatmentwith the different concentration of CGRP_8-37,RP67580and CGRP_8-37+RP67580can significantly enhance AAR/LV%.3. The effection of CGRP and SP to cardiac hemodynamics of reperfusion afterIpostC:Compared with group IR èIpostC significantly reduce SAP,DAP and PAP,significantly enhanced HR; compared with group IpostC, pretreatment with CGRP_8-37can significantly increased SAP and DAP, prominently reduce HR and PAP;pretreatment with RP67580can significantly increased SAP and DAP, prominentlyreduce HR and PAP; pretreatment with CGRP_8-37+RP67580can significantlyenhanced LVSP and DAP, produced lower HR.4.The effection of CGRP and SP to ventricular arrhythmia of reperfusion after IpostC:Compared with group IR ècardiac ventricular arrhythmia was significantlydecreased in group IpostC., the duration of arrhythmias was late; compared withgroup IpostC, pretreatment with the different concentration of CGRP_8-37,RP67580and CGRP_8-37+RP67580can significantly increase ventricular arrhythmia, theduration of arrhythmias was bring forward.Conclusions: Results from the present study indicate that IpostC could increase theexpress of endogenous CGRP and SP, regulate cardiac functions, arrhythmias andmyocardial infarction after Ischemia-reperfusion, endogenous CGRP and SP might beinvolved in the regulation of the effect through their specific receptor.However, theprecise mechanisms involved remain elusive.