Effect Of Delayed Preconditioning Combined With Early Preconditioning Of Sufentanil On Myocardial Ischemia Reperfusion Injury And Caspase-3in Rats

Objective Through setting up big mouse’s myocardial ischemia reperfusion injury animal’s model, to investigate the effect of early preconditioning and delayed preconditioning of sufentanil on myocardial ischemia reperfusion injury in rats.Methods The rat models of myocardial ischemia reperfusion was established with occlusion of the left anterior descending coronary artery(LAD) for40min and reperfusion for120min.80adult male Wister rats were randomly divided into5groups(16every group):Sham operation group(S group), Ischemia/reperfusion group(I/R group), Sufentanil delayed preconditioning group(SF1group), Sufentanil early preconditioning group(SF2group), Sufentanil delayed preconditioning with early preconditioning group(SF1+SF2group).24hours prior ischemia reperfusion, the animals received1ml of normal saline in S group, I/R group, and SF2group, the animals received Sufentanil5μg/kg with1ml of normal saline in SF1group and SF1+SF2group I.P.24hours later, I/R was induced by clamping the left anterior descending artery for40minutes in I/R and SF groups.15minutes prior I/R, SF2group and SF1+SF2group received Sufentanil5μg/kg with1ml of normal saline I.V., and S group, I/R group, and SF2group received1ml of normal saline I.V. The heart rate(HR), mean arterial pressure(MAP) and the product of HR and MAP (RPP) were continually monitored, and recorded at the base line(To), the end of ischemia(T1) and post reperfusion30min(T2),60min(T3) and120min(T4) respectively; the value of cardiac troponin I(cTnI) was measured at the base line, the end of ischemia and reperfusion. At the end of reperfusion,8rats were selected randomly from each g-roup to measure myocardial infraction size (infraction size, IS) through double-staining with Evan’s blue and TTC. Cardiac specimen was taken from the other eight rats in each g-roup, the pathological changes of myocardium were observed with microscope and transmission electron microscope, the expressions of caspase-3in the myocardium of ischemia area were measured by Immunohistochemistry assay, apoptosis index(AI) of myocardium was detected by TUNELResults1. HR, MAP and RPP:There was no statistically difference in HR, MAP and RPP among all groups at the baseline (P>0.05). Compared with the baseline, HR, MAP and RPP of I/R group and all SF groups obviously decreased during the period of ischemia and reperfusion (P<0.01). During the period of ischemia and reperfusion, compared with S group, HR, MAP and RPP were obviously decreased in I/R group and all SF groups (P<0.01), but no significant difference among different SF groups and I/R group(P>0.05).2. cTnI:There was no statistically difference in the level of cTnI among all groups during the baseline (P＞0.05). At the end of ischemia and reperfusion, compared with the baseline, the level of cTnl I/R group and all SF groups increased remarkably(P<0.01). At the end of ischemia and reperfusion, the level of cTnI of I/R and all SF groups was significantly higher than that of S group(P＜0.01), the level of cTnI of all SF group was significantly lower than that of I/R group(P＜0.01), the level of cTnI of SF1+SF2group was significantly lower than that of SF1and SF2group(P<0.05),but no significant statistically difference between SF1and SF2group (P>0.05).3. myocardial infraction size, the expressions of caspase-3, apoptosis index (AI): Compared with S group, myocardial infraction size, the expressions of caspase-3, apoptosis index in both I/R group and all SF group increased remarkably and significantly(P<0.01). Compared with I/R group, myocardial infraction size reduced remarkably, and the expressions of caspase-3, apoptosis index decreased remarkably in all SF groups(P<0.01).Compared with SF1+SF2group, myocardial infraction size further reduced, the expressions of caspase-3, apoptosis index further decreased in both SF1and SF2group(P<0.01). There was no significant statistically difference between SF1and SF2group (P＞0.05).4. myocardial ultrastructure:Compared with S group, remarkable injury of myocardial ultrastructure was observed in both I/R group and all SF group. Compared with I/R group, the injury of myocardial ultrastructure significantly reduced in all SF groups. Compared with SF1and SF2group, the injury of myocardial ultrastructure further reduced in SF1+SF2group.Conclusions Sufentanil delayed preconditioning with early preconditioning reduced I/R injury, the protective effect was better than either Sufentanil early preconditioning or Sufentanil delayed preconditioning of I/R injury in rat.