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1. In the present study, we investigated the effect of 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone), a free radical scavenger, on myocardial infarct (MI) size and cardiac function in an in vivo model of MI in rabbits. We further investigated the contribution of hydroxyl radicals, superoxide and nitric oxide (NO) to its effects. 2. Anaesthetized open-chest Japanese white male rabbits were subjected to 30 min coronary occlusion and 48 h reperfusion. The control group ( n = 10) was injected with saline 10 min before reperfusion. The edaravone group ( n = 10) was injected with a bolus of 3 mg/kg edaravone 10 min before reperfusion. The edaravone +  NG-nitro-l-arginine methyl ester (l-NAME) group ( n = 5) was given 10 mg/kg, i.v.,l-NAME 10 min before the administration of 3 mg/kg edaravone. Thel-NAME group ( n = 5) was given 10 mg/kg, i.v.,l-NAME 20 min before reperfusion. Infarct size was measured using the triphenyl tetrazolium chloride method and is expressed as a percentage of area at risk. Cardiac function was assessed by echocardiography 14 days after infarction. 3. In another series of experiments, rabbits were subjected to 30 min coronary occlusion and 30 min reperfusion and myocardial interstitial 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA levels, indicators of hydroxyl radical, were measured using a microdialysis technique. 4. Infarct size in the edaravone group was significantly reduced compared with that in the control group (27.4 ± 6.8 vs 43.4 ± 6.8%, respectively; P < 0.05). The edaravone-induced reduction of infarct size was abolished by pretreatment withl-NAME. Myocardial interstitial levels of 2,3-DHBA and 2,5-DHBA increased 20 and 30 min after ischaemia and peaked at 10 min reperfusion in the control group. Edaravone significantly inhibited the increase in 2,3-DHBA and 2,5-DHBA levels seen during reperfusion. Dihydroethidium staining showing in situ detectoion of superoxide was less intense in ischaemic myocardium in the edaravone-treated group compared with the control group. Edaravone improved cardiac function and left ventricular remodelling 14 days after infarction. 5. In conclusion, edaravone significantly reduces MI size and improves cardiac function and LV remodelling by decreasing hydroxyl radicals and superoxide in the myocardium and increasing the production of NO during reperfusion in rabbits. [ABSTRACT FROM AUTHOR]

Summary 1. Diabetes mellitus is significantly associated with the occurrence of congestive heart failure in end-stage renal disease patients undergoing maintenance haemodialysis. In the present study, we asked whether the left ventricular remodelling against sustained pressure and/or volume overload to the left ventricle may be different between diabetic and non-diabetic haemodialysis patients. 2. Left ventricular parameters, including left ventricular mass index (LVMI), interventricular septal wall thickness (IVST) and relative left ventricular wall thickness (rLVWT), were assessed in 486 patients receiving maintenance haemodialysis (145 diabetic and 341 non-diabetic patients) using transthoracic echocardiography. Plasma concentrations of B-type natriuretic peptide (BNP), measured with an immunoradiometric assay, were used as a humoral parameter indicating left ventricular wall stress. 3. In non-diabetic patients, the plasma BNP concentration correlated with LVMI (r = 0.245; P = 0.0001), IVST (r = 0.250; P = 0.0001) and rLVWT (r = 0.149; P = 0.006). Furthermore, LVMI was correlated with mean blood pressure and pulse pressure and IVST and rLVWT were correlated with pulse pressure. 4. In contrast, none of the measured factors was correlated with LVMI and IVST in diabetic patients. Plasma BNP concentrations were positively correlated with end-systolic and end-diastolic left intraventricular dimensions and were inversely correlated with rLVWT and left ventricular fractional shortening in diabetic patients, but not in non-diabetic patients. 5. In conclusion, a sustained increase in left ventricular wall stress is likely to elicit eccentric left ventricular remodelling in diabetic haemodialysis patients, whereas it causes concentric left ventricular remodelling in non-diabetic haemodialysis patients. This difference in left ventricular remodelling against left ventricular overload may be associated with the high incidence of congestive heart failure in diabetic haemodialysis patients. [ABSTRACT FROM AUTHOR]