| Objective: Myocardial ischemia preconditioning (IPC) is a powerful endogenouscardioprotective mechanism against ischemia/reperfusion (I/R) injury, but whetherIPC have cardioprotections in diabetes mellitus is disputed at present. Ramiprilprotects myocardium from I/R injury in normal rats, and it's also can decrease theincidence of cardiovascular disease of diabetes mellitus patients. This study wasdesigned to evaluate whether IPC and ramipril can protect myocardium ofexperimental diabetic rats from I/R injury.Methods: Seventy-five healthy mate Wistar rats were divided randomly into sixgroups and subjected to difference treatments.Ramipril(1mg/kg/day) was given to ratsin RAM+DM+I/R group and RAM+DM+IP group for 4 weeks. The same volume ofnormal saline was given to rats in I/R group, IP group, DM+I/R group and DM+IPgroup.After four weeks of intragastric administration, all rats were subjected toopen-chest surgery. A ligature was passed below the left anterior descending coronaryartery (LAD) to form a snare. The LAD of rats in I/R, DM+I/R and RAM+DM+I/Rgroups were induced by ligation for 30 minutes followed by reperfusion for 2 hours.While in IP, DM+IP and RAM+DM+IP groups, the LAD of rats were occluded threetimes each for 5 minutes, followed by reperfusion for 5 minutes (IPC) before ligationfor 30 minutes. Arrhythmia corresponding to ischemic injury, heart rate, bloodpressure and ST-segment in ECG were recorded continuously throughout the wholetest. TTC staining was performed to determine myocardial necrosis at the end ofreperfusion. Cardiomyocyte apoptosis was assessed by terminal deoxyribonucleotidyltransferase-mediated dUTP nick-end labeling assay. The expression of antiapoptoticgene (Bcl-2) and proapoptotic gene (Bax) was determined by immunohistochemistry.Result:1. Cardioprotections of IPC in non-DM rats In I/R group, the myocardial injury was severe: the ST-segment corresponding toischemic injury was elevated significantly(0.527±0.107mV). The onsets ofventricular premature contraction(VPC) were early(1.96±1.75min), the durations ofVPC were long(20.67±7.42min). The incidence of ventricular tachycardia(VT) andventricular fibrillation(VF) was high(60％, 60％), The myocardial infarct size wasextensive (32.98±10.99％). TUNEL assay demonstrated that cardiomyocyte apoptosisindex(AI)was high, and the ratio of Bcl-2/Bax was low.Compared with I/R group, the elevation of ST-segment was decreased (0.285±0.042 vs 0.527±0.107mV, P＜0.001), the onset of VPC was delayed (14.29±4.81 vs1.96±1.75min, P＜0.001), the duration of VPC was shortened (8.11±3.52 vs20.67±7.42min, P＜0.001) and the incidence of VT and VF was decreased (10％vs60％, P＜0.05; 0 vs 60％, P＜0.01, respectively) remarkably in IP group. Themyocardial infarct size was reduced significantly (15.86±3.02％vs 32.98±10.99％,P＜0.01) as well. Cardiomyocyte AI was attenuated in IP group (8.09±2.38％vs16.68±3.35％, P＜0.001), correlating with increased the ratio of Bcl-2/Bax(0.951±0.060 vs 0.421±0.105, P＜0.001).2. Comparison of I/R in non-DM and experimental DM ratsCompared with I/R group, the onset and duration of VPC(6.32±4.44 vs1.96±1.75min, P＞0.05; 16.35±5.63 vs 20.67±7.42min, P＞0.05, respectively), and theincidence of VT and VF (60％vs 60％, P＞0.05; 50％vs 60％, P＞0.05, respectively)were not different in DM+I/R group. The myocardial infarct size was not exaggeratedsignificantly (34.41±12.60％vs 32.98±10.99％, P＞0.05) as well.But the elevation ofST-segment was increased (0.675±0.154 vs 0.527±0.107mV, P＜0.01). CardiomyocyteAI was potentized in DM+I/R group (25.56±3.06％vs 16.68±3.35％, P＜0.001),correlating with decreased the ratio of Bcl-2/Bax (0.105±0.065 vs 0.421±0.105,P＜0.001). 3. Cardioprotections of IPC in experimental DM ratsCompared with DM+I/R group, the elevation of ST-segment was decreased(0.489±0.169 vs 0.675±0.154mV, P＜0.05), the onset of VPC was delayed (17.92±5.49 vs 6.32±4.44min, P＜0.001), the duration of VPC was shortened (6.14±4.78 vs16.35±5.63 min, P＜0.01) and the incidence of VT and VF was decreased (10％vs60％, P＜0.05; 10％vs 50％, P＜0.05, respectively) remarkably in DM+IP group. Themyocardial infarct size was reduced significantly (17.16±10.03％vs 34.41±12.60％,P＜0.01) as well. Cardiomyocyte AI was attenuated in DM+IP group (20.24±4.22％vs 25.56±3.06％, P＜0.001), correlating with increased the ratio of Bcl-2/Bax(0.221±0.101 vs 0.105±0.065, P＜0.05).4. Cardioprotections of Ramipril in experimental DM ratsCompared with DM+I/R group, the elevation of ST-segment was decreased(0.422±0.155 vs 0.675±0.154mV, P＜0.01), the onset of VPC was delayed (12.12±6.33 vs 6.32±4.44min, P＜0.05), the duration of VPC was shortened (10.27±5.24 vs16.35±5.63min, P＜0.05) and the incidence of VT and VF was decreased (30％vs60％, P＜0.05; 0 vs 50％, P＜0.05, respectively) remarkably in RAM+DM+I/R group.The myocardial infarct size was reduced significantly (15.35±7.26％vs 34.41±12.60％, P＜0.01) as well. Cardiomyocyte AI was attenuated in RAM+DM+I/R group(18.19±3.12％vs 25.56±3.06％, P＜0.001), correlating with increased the ratio ofBcl-2/Bax (0.269±0.162 vs 0.105±0.065, P＜0.01).Compared with DM+I/R group, the elevation of ST-segment was notdecreased(0.608±0.224 vs 0.675±0.154mV, P＞0.05), but the onset of VPC wasdelayed (11.10±2.72 vs 6.32±4.44min, P＜0.05), the duration of VPC was shortened(8.77±5.34 vs 16.35±5.63min, P＜0.05) and the incidence of VT and VF wasdecreased (10％vs 60％, P＜0.05; 10％vs 50％, P＜0.05, respectively) remarkably inRAM+DM+IP group. The myocardial infarct size was reduced significantly (16.90± 11.51％vs 34.41±12.60％, P＜0.01) as well. Cardiomyocyte AI was attenuated inRAM+DM+IP group (19.80±4.18％vs 25.56±3.06％, P＜0.001), correlating withincreased the ratio of Bcl-2/Bax (0.216±0.201 vs 0.105±0.065, P＜0.05).In RAM+DM+I/R group, compared with that of DM+IP group, the elevation ofST-segment, the onsets and durations of VPC, the incidence of VT and VF, themyocardial infarct size were no difference in statistics. Cardiomyocyte AI and theratio of Bcl-2/Bax were also no difference in statistics.In RAM+DM+IP group, compared with that of DM+IP group, the elevation ofST-segment, the onsets and durations of VPC, the incidence of VT and VF, themyocardial infarct size were no difference in statistics. Cardiomyocyte AI and theratio of Bcl-2/Bax were also no difference in statistics.Conclusions:1. Compared with the myocardial ischemia/reperfusion injury in non-DM rats,the injury of experimental DM rats was more severe partly.2. IPC can protect myocardium from I/R injury in experimental DM rats,including reduction of the severity of arrhythmias, myocardial infarct sizeand cardiomyocyte apoptosis induced by ischemia.3. Ramipril can protect myocardium from I/R injury in experimental DM rats,including reduction of the severity of arrhythrnias, myocardial infarct sizeand cardiomyocyte apoptosis induced by ischemia, and its intensity issimilar with IPC.4. There is no synergitic effect between Ramipril and IPC. |
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