Effect of superoxide dismutase on infarct size and postischemic recovery of myocardial contractility and metabolism in dogs.
The effects of superoxide dismutase treatment on infarct size, postischemic recovery of contractile function and tissue content of high energy phosphates were examined in a canine model of myocardial ischemia and reperfusion. Ischemia was induced by thrombotic occlusion of a coronary artery and reperfusion was achieved by intravenous thrombolysis. Average duration of ischemia was 90 min. Fifty closed chest anesthetized dogs were randomized to receive either superoxide dismutase (34,000 IU/min intravenously) or placebo, starting approximately 30 min before and continuing for 30 min into the reperfusion phase. Left ventricular ejection fraction and regional segmental shortening of the postischemic area were calculated from contrast angiograms after 4 h, 48 h and 1 week of reperfusion. Tissue content of high energy phosphates was determined from transmural biopsy after 4 h and 1 week. Infarct size was measured by planimetry of dye-stained heart slices. In the superoxide dismutase and placebo-treated groups, respectively, the mortality rate was 25% and 16%, collateral flow 20 +/- 10 and 23 +/- 18 ml/min per 100 g, area at risk 25 +/- 6% and 26 +/- 7% of the left ventricle and infarct size 28 +/- 19% and 36 +/- 27% of the area at risk. Multiple regression analysis failed to show any beneficial effect of superoxide dismutase treatment on infarct size. Left ventricular ejection fraction, regional segmental shortening of the postischemic area and tissue content of high energy phosphates recovered to a similar extent and at a similar rate in both treated and placebo groups up to 1 week after reperfusion. Thus, in this model of coronary occlusion and reperfusion superoxide dismutase treatment is of no benefit.
Vanhaecke
J
J
Laboratory of Experimental Cardiology, University of Leuven, Belgium.
Van de Werf
F
F
Ronaszeki
A
A
Flameng
W
W
Lesaffre
E
E
De Geest
H
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004285:Dogs; D004792:Enzyme Precursors / Q000627:therapeutic use; D005260:Female; D016166:Free Radical Scavengers; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010960:Plasminogen Activators / Q000627:therapeutic use; D011994:Recombinant Proteins; D012044:Regression Analysis; D013482:Superoxide Dismutase / Q000627:therapeutic use*; D015912:Thrombolytic Therapy; D014568:Urokinase-Type Plasminogen Activator / Q000627:therapeutic use
D004792:Enzyme Precursors; D016166:Free Radical Scavengers; D011994:Recombinant Proteins; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; C067551:saruplase