The Effects Of Delayed Sevoflurane Postconditioning On Myocardial-reperfusion Injury In Isolated Rat Hearts

Objective:1. To investigate the protective effects of sevoflurane postconditioning and deplayed sevoflurane postconditioning on an isolated rat heart model.2. To investigate the effective time window of protective effect of deplayed sevoflurane postconditioning on an isolated rat heart model.3. Preliminarily explore the protective mechanism of deplayed sevoflurane postconditioning on an isolated rat heart model.Methods:1. Isolated SD rat hearts were balanced for15min and then randomly assigned to the following10groups:(1)Time Control (TC) group;(2) Ischemia/reperfusion (I/R) group;(3) Sevoflurane postconditioning (SpostC) group;(4) Delayed0.5min Sevofluranepostconditioning (S0.5) group;(5:) Delayed1min Sevofluranepostconditioning (SI) group;(6) Delayed3min Sevofluranepostconditioning (S3) group;(7) Delayed5min Sevofluranepostconditioning (S5) group;(8) Delayed10min Sevofluranepostconditioning (S10) group;(9) Delayed20min Sevofluranepostconditioning (S20) group;(10) Delayed30min Sevoflurane postconditioning (S30) group. To campare the differences of hemodynamics, infarct size, cardiac troponin I levels and Akt phosphorylation levels among groups.2. Isolated SD rat hearts were balanced for15min and then randomly assigned to the following7groups:(1)TC group;(2) I/R group;(3) SpostC group;(4) S1group;(5) S10group;(6)S20group;(7)S30group.To campare the differences of infarct size, myocardial apoptosis levels, GSK-3phosphorylation levels and the open of mitochondrial permeability transition pore among groups.Results:1、Hemodynamics:compared with the I/R group, the HR、LVDP、dp/dt and-dp/dt of the first six groups have obvious differences in reperfusion30min、60min、120min (P<0.05), the difference between partly time point of S30group and I/R group was not statistically significant (P>0.05)2、Cardiac troponin I levels:compared with the I/R group,the Cardiac troponin I levels of the first seven groups obviously decrease in reperfusion120min (P<0.05), compared with the Spost group, S20group and S30group, the Cardiac troponin I levels have significantly increased (P<0.05)3、Infarct size:Infarct size of nine groups respectively were44%±5.8%,20%±2.8%,23%±5.7%,22%±4.7%,25%±3.9%,32%±5.8%,30%±5.8%,,34%±4.2%and39%±4.9%.The first seven groups significantly lower than the I/R group(P<0.05),the last group has no significant difference with the I/R group(P>0.05)4、 Akt phosphorylation levels:compared with the I/R group,each group’s Akt phosphorylation expression levels were significantly increased(P<0.05)5、GSK-3phosphorylation levels:The expression levels of the first five groups significantly increased compared with the I/R group(P<0.05).The expression levels of S1group、S10group and S20group have no significant difference with the Spost group(P>0.05).S30group lower than the Spost group(P<0.05)6、NAD+levels of myocardial tissue:A significant increase in the danger zone of left ventricular myocardial tissue levels of NAD+compared with the I/R group,there were significant differences(P<0.05).This parameter of the S10group、S20group、 and S30group was significantly decreased compared with the Spost group.Conclusion1、Sevoflurane postconditioning and deplayed sevoflurane postconditioning in vitro rat cardiac ischemia-reperfusion injury has a protective effect, they can improve hemodynamics after reperfusion of the heart, reduce myocardial cTnl release, decrease infarct size and cardiac myocardial apoptosis. 2、The protective effect of deplayed sevoflurane postconditioning on vitro rat cardiac ischemia-reperfusion injury should have time windows, when the delay time is30min, myocardial protective effect of deplayed sevoflurane postconditioning disappeared.3、The protective effect of deplayed sevoflurane postconditioning on vitro rat cardiac ischemia-reperfusion injury may be associated with Akt and GSK-3β phosphorylation levels and inhibiting mPTP opening on myocardial cells.