| Objective:To investigate the protection of ramipril, BQ-123 and their combination against myocardial ischemia/reperfusion (I/R) injury in vivo in anesthetized rats, and explore the role of myocardial oxidation-antioxidation system.Methods:Seventy-two healthy male Wistar rats were divided into 5 groups randomly:sham operated (sham) group, I/R group, ramipril (RAM) group, BQ-123 (BQ) group and ramipril and BQ-123 (R&B) group. All groups but not sham were subjected to 30 min ischemia/120 min reperfusion through ligation of the left anterior descending (LAD) coronary artery. Ramipril (1 mg/kg) was given orally to rats in RAM and R&B groups twenty four hours before I/R. The same volume of normal saline was given to rats in other groups. BQ-123 (10μg/kg/min) was infused intravenously from 10 min before ligation to the end of 30 min ischemia to rats in BQ and R&B groups during I/R procedue. The same volume of normal saline was given to other groups. Rats in sham group were not subjects to I/R procedure. Heart rate (HR), blood pressure and lead II electrocardiogram were monitored throughout the experiment and ventricular arrhythmia (VA) was recorded during ischemia. Myocardial infarct size was measured by TTC staining. Changes of myocardial morphology were observed after HE staining. Activity of plasma creatine kinase (CK) and lactate dehydrogenase (LDH), myocardial total superoxide dismutase (T-SOD), manganese superoxide dismutase (Mn-SOD) and catalase (CAT) and content of myocardial malondialdehyde (MDA) were detected by spectrophotometer.Results:1. Effects of ramipril and BQ-123 on myocardial I/R injury in ratsIn I/R group, the elevation of ST-segment was dramatically increased (P<0.001); onset of ventricular premature contraction (VPC) and ventricular tachycardia (VT) were 5.11±0.78 and 6.05±1.65 min, durations of them were 20.60±3.08 and 14.19±5.37 min; incidences of VPC, VT and ventricular fibrillation (VF) were 100% respectively; activity of plasma CK and LDH was significantly enhanced; infarct size/area at risk (IS/AAR) and IS were 38.76±4.63% and 82.51±8.66 mg; the activity of T-SOD, Mn-SOD and CAT was 150.84±13.89,52.68±8.82 and 2.48±0.70 U/mgprot respectively. MDA content was 2.77±0.18 nmol/mgprot.Compared with I/R group, the parameters in RAM and BQ groups were changed dramatically. The elevation of ST-segment was decreased (P<0.01), onset of VPC (9.88±1.98; 7.77±0.87) and VT (10.60±1.41; 8.60±0.57 min) were delayed, durations of VPC (9.10±1.61; 6.97±1.95 min) and VT (5.08±1.49; 4.90±1.36 min) were shortened, incidences of VPC, VT and VF were decreased. Activity of plasma CK and LDH was decreased. IS (46.99±9.94; 40.79±8.01 mg), IS/AAR (22.68±3.24; 19.85±3.68%), activity of T-SOD (168.55±11.93; 170.90±12.85 U/mgprot), Mn-SOD (78.11±8.78; 80.02±9.72 U/mgprot) and CAT (3.80±0.66; 3.83±0.39 U/mgprot) were increased respectively. MDA content (1.77±0.06; 1.68±0.09 nmol/mgprot) was decreased. The morphology of myocardium was improved.2. Effects of ramipril in combination with BQ-123 on myocardial I/R injuryCompared with I/R group, the R&B group was changed dramatically. The elevation of ST-segment was decreased (P<0.001); onset of VPC (9.53±1.89 min) and VT (8.80±1.39 min) were delayed, durations of VPC (7.15±1.85 min) and VT (4.84±1.34 min) were shortened; incidences of VT (44%) and VF (13%) were decreased; activity of plasma CK and LDH was significantly degraded; IS (30.64±6.43 mg) and IS/AAR (15.62±5.00%) were decreased; activity of T-SOD (192.12±10.70 U/mgprot), Mn-SOD (102.85±11.73 U/mgprot) and CAT (4.36±0.60 U/mgprot) was increased; MDA content (1.51±0.08 nmol/mgprot) was decreased. The morphology of myocardium was improved.Compared with RAM and BQ groups, the parameters of R&B group were changed dramatically. Mean arterial blood pressure (MAP) was increased in reperfusion 30 and 120min (P<0.001); activity of plasma CK in ischemia 30 min and LDH in reperfusion 120 min were both decreased (P<0.001); IS, IS/AAR and MDA content were decreased respectively. Activity of T-SOD and Mn-SOD was increased. The morphology of myocardial was improved. And compared with BQ group, onset of VPC was delayed (P<0.01); compared with RAM group, duration of VPC was shorten (P<0.05), onset of VT was earlier (P<0.05).Conclusions:1. The results documented that ramipril, BQ-123 and ramipril in combination with BQ-123 protected myocardium from I/R injury by decreasing the elevation of ischemia-induced VA and ST-segment, decreasing the release of CK and LDH and MDA content, increasing the activity of SOD and CAT.2. The protective effects on decreasing the release of CK and LDH, reducing necrosis of cardiomyocytes and increasing the activity of SOD and decreasing MDA content were better than using ramipril and BQ-123 alone.3. It was the first time to investigate the protective effects of ramipril in combination with BQ-123 on myocardial I/R oxidative injury in vivo. The results demonstrated that combined using these two agents may protect myocardium from I/R oxidative injury. The mechanism of protective effects was associated with the increase in antioxidative ability of myocardium. |
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