Beneficial effects of nafazatrom on ischemic reperfused myocardium.
The effect of nafazatrom, a new antithrombotic agent, was studied in a canine model of regional myocardial ischemia. Nafazatrom was administered 1 mg/kg intravenously every 6 h for 48 h. After 24 h of drug or placebo administration, animals underwent 90 min of occlusion of the proximal left circumflex coronary artery followed by gradual reperfusion over a period of 30 min. Twenty-four hours later, the animals were sacrificed and infarct size was determined by histochemical staining with triphenyltetrazolium chloride. Nafazatrom-treated animals had a significant reduction in infarct size expressed as a percent of the anatomical area at risk for infarction: 21 +/- 5% in the treated group vs. 41 +/- 5% in the control group (X +/- S.E.M., P less than 0.05). Histological examination confirmed the gross results of postmortem histochemical staining. Salvage of ischemically jeopardized tissue appeared to be unrelated to myocardial oxygen demand as there were no hemodynamic differences between groups. The beneficial effects of nafazatrom are presumably related to a limitation of autolytic processes on the heart during and after ischemia as a result of the drug's ability to inhibit lipoxygenase and to prevent the enzymatic degradation of prostacyclin.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D004562:Electrocardiography; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology; D011720:Pyrazoles / Q000627:therapeutic use*; D047069:Pyrazolones; D013997:Time Factors
D005343:Fibrinolytic Agents; D011720:Pyrazoles; D047069:Pyrazolones; C018845:nafazatrom