The Research Of The Cardioprotective Effect Of The Combination Of Isoflurane And Captopril Preconditioning Against Myocardial Ischemia And Reperfusion Injury In Rabbit

Objective:To investigate the cardioprotective effect of the combina-tion of isoflurane and captopril preconditioning on myocardial ischemia reperfusion injury in rabbit.Methods:All healthy New Zealand white rabbits were randomly assigned to six groups (n=8 each):(1) Sham-operated group(group S), rabbits were opened chest without ligating the left anterior descending coronary artery (LAD); (2) Ischemia/reperfusion group (group I/R) group; (3) Ischemic preconditioning group (group IPC),5min ischemia-5min reperfusion for three cycles before the long time ischemia; (4) Isoflurane group (groupⅠ), rabbits were pretreated with 30min end-tidal 1.1% isoflurane and 15min of washout; (5) Captopril group(group C), rabbits were feeded captopril tablets (25 mg·kg-1) before 24h; (6) Combination of isoflurane and captopril preconditioning group(group I+C), rabbits were feeded captopril tablets (25mg·kg-1) before 24h and pretreated with 30min end-tidal 1.1% isoflurane and 15min of washout after 24h. After preconditioning, all rabitts were treated 30min of ischemia and 2h of reperfusion except for group S. Hemodynamic parameters and incidence rate of arrhythmia were recorded at before ischemia (To),30min after ischemia (T1),30min after reperfusion(T2),60min after reperfusion(T3) and 120min after reperfusion(T4). Blood samples were taken from arterial line for determination of plasma CK, CK-MB, LDH and cTnI levels. At the end of the reperfusion, the plasma concentration of MDA and activity of SOD were examined and myocardial structure was observed under light and electron microscope.Results:Heart Rate(HR) of group I+C was significantly higher than other groups and Mean Arterial Pressure (MAP) was lower (P<0.05 or P＜0.01). And incidence rate of arrhythmia was lower in group I+C (P＜0.05). The CK, CKMB, LDH and cTnI levels of group IPC and group I+C were significantly lower than that of groupⅠ, group C and group I/R (P＜0.05), but were higher than group S (P＜0.05). The injury of group I/R was worse than the others from the changes of the cellular structure under light and electron microscope. Group IPC and group I+C had lower concentration of MDA and also had higher activity of SOD than other groups except for group S.Conclusions:The combination of isoflurane and captopril pre-conditioning induces cardioprotection against ischemia reperfusion injury in rabbits. The cardioprotection was better than that of solitary preconditioning and similar with that of group IPC.Objective:To investigate the effect of the combination of isoflurane and captopril preconditioning on myocardial infarct size(IS) and apoptosis during ischemia-reperfusion in rabbit.Methods:All healthy New Zealand white rabbits were randomly assigned to six groups(n=8 each):(1) Sham-operated group(group S), rabbits were opened chest without ligating the left anterior descending coronary artery; (2) Ischemia/reperfusion group(group I/R); (3) Ischemic preconditioning group(group IPC),5min ischemia-5min reperfusion for three cycles before the long time ischemia; (4) Isoflurane group (groupⅠ), rabbits were pretreated with 30min end-tidal 1.1% isoflurane and 15min of washout; (5) Captopril group(group C), rabbits were feeded captopril tablets (25mg·kg-1) before 24h; (6) Combination of isoflurane and captopril preconditioning group(group I+C), rabbits were feeded captopril tablets (25mg·kg-1) before 24h and pretreated with 30min end-tidal 1.1% isoflurane and 15min of washout after 24h. After preconditioning, all rabitts were treated 30min of ischemia and 2h of reperfusion except for group S. At the end of the reperfusion, infarct size(IS) and area at risk(AAR) were accessde by Evans Blue and TTC staining. Apotosis index were detected by flow cytometry.Results:Myocardial infarct size of group IPC, groupⅠ, group C and group I+C (33.6±3.8%,39.8±5.7%,39.6±3.4%,33.9±5.9%) were less than that of group I/R (60.7±6.0, P<0.01). Myocardial infarct size of group IPC and group I+C were less than that of groupⅠand group C (P<0.05), but distinction between group IPC and group I+C was not significantly (P>0.05). Apoptotic index of group S was the lowest in eath group (P＜0.01). Apoptotic index of group I/R was less than that of group IPC, group I, group C and group I+C(P<0.01). Apoptotic index of group I+C was less than that of groupⅠand group C, but not different with that of group IPC (P＜0.05).Conclusions:The combination of isoflurane and captopril preconditioning can reduce myocardial infarct size and the incidence rate of apoptotic during ischemia reperfusion in rabbits. The effect was better than that of solitary preconditioning and similar with that of group IPC. The combination of isoflurane and captopril preconditioning produced a synergistic protective effect of anti-apoptosis.Objective:To investigate the effect of the combination of isoflurane and captopril preconditioning on apoptosis-related gene and apoptosis pathway during myocardial ischemia and reperfusion in rabbit.Methods:All healthy New Zealand white rabbits were randomly assigned to six groups (n=8 each):(1) Sham-operated group(group S), rabbits were opened chest without ligating the left anterior descending coronary artery; (2) Ischemia/reperfusion group(group I/R); (3) Ischemic preconditioning group (group IPC),5min ischemia-5min reperfusion for three cycles before the long time ischemia; (4) Isoflurane group (groupⅠ), rabbits were pretreated with 30min end-tidal 1.1% isoflurane and 15min of washout; (5) Captopril group (group C), rabbits were feeded captopril tablets (25 mg·kg-1) before 24h; (6) Combination of isoflurane and captopril preconditioning group (group I+C), rabbits were feeded captopril tablets (25 mg·kg-1) before 24h and pretreated with 30min end-tidal 1.1% isoflurane and 15min of washout after 24h. After preconditioning, all rabitts were treated 30min of ischemia and 2h of reperfusion except for group S. At the end of the reperfusion, the heart was harvested and the activity of apoptosis-related gene (Bcl-2 and Bax) and apoptosis pathway proteins (caspase-3, caspase-8 and caspase-9) were determined by Western Blot analysis, apotosis index was detected by flow cytometry.Results:Bcl-2/Bax ratio of group I+C and group IPC was higher than that of groupⅠand group C (P<0.01). But Bcl-2/Bax ratio of group I+C was the same high as that of group IPC. The activity of caspase-3, caspase-8 and caspase-9 of every preconditioning group were lower than that of group I/R. The activity of caspase-8 of group I+C was lower than that of other preconditioning group. The activity of caspase-9 of group IPC was lower than that of drug preconditioning group. Apotosis index of every preconditioning group was lower that of group I/R(P<0.01). Apotosis index of group I+C was lower that that of group I and group C, but ot different with that of group IPC (P>0.05).Conclusions:The combination of isoflurane and captopril preconditioning can promote the activity of Bcl-2, inhibit the activity of Bax and increase Bcl-2/Bax ratio in myocardium during ischemia reperfusion, which maybe one of molecular mechanisms of the combina-tion of isoflurane and captopril preconditioning on cardioprotection. The combination of isoflurane and captopril preconditioning can inhibit the activity of caspase-3, caspase-8 and caspase-9 and signal transduction of apoptosis pathway, which indicate that the combination of isoflurane and captopril preconditioning can inhibit mitochondrion pathway and death receptor pathway, but mainly the latter.