© 1992 by European Society of Cardiology
Copyright © 1992, European Society of Cardiology
Effects of reperfusion and superoxide dismutase on myocardial infarct size in a closed chest pig model
Department of Internal Medicine, University Hospital, S-901 85 Umeå, Sweden: U Näslund;
Department of Anaesthesiology, University Hospital, S-901 85 Umeå, Sweden: S Häggmark, G Johansson, S Reiz
Department of Clinical Chemistry, University Hospital, S-901 85 Umeå, Sweden: S Marklund
Clinical Research Unit, ICI-Pharma AB, Gothenburg, Sweden: Sweden: K Pennert
Corresponce to Dr Näslund.
Objective: The aim was to study the effects on myocardial infarct size of reperfusion alone or of CuZn superoxide dismutase (SOD) as an adjunct to reperfusion. Methods: Occlusion was induced in closed chest, pentobarbitone anaesthetised, mechanically ventilated pigs by injection of a 2 mm ball into a preselected coronary artery. Reperfusion was achieved by retraction of the ball via an attached filament. Twenty nine placebo treated and 25 SOD treated animals were subjected to 30 (n=21), 60 (n=21), and 90 (n=12) min of coronary occlusion followed by reperfusion to 24 h; a control group of 24 pigs was subjected to a sustained occlusion for 24 h. Infarct size was assessed by tetrazolium staining and plasma creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LD). In the CuZn SOD group, 200 mg bovine CuZn SOD was given as a bolus intravenously immediately before reperfusion followed by a continuous infusion (100 mg) for 60 min. The size of the ischaemic myocardium at risk was measured from post mortem autoradiograms. Results: Infarct size as percent of myocardium at risk was 46.0(SD 15.5)%, 80.1(9.9)%, and 88.9(5.0)% respectively in placebo animals with 30, 60, and 90 min occlusion, and 94.2(5.1)% in pigs with 24 h sustained occlusion. Compared to 24 h sustained occlusion, limitation of infarct size by reperfusion was only demonstrated in the 30 (p<0.001) and 60 min groups (p<0.001). Plasma values of CK, ASAT, and LD at 90 min post-reperfusion correlated closely with infarct size as assessed by tetrazolium staining and were related to occlusion duration. No myocardial salvage, as assessed by plasma ASAT, CK, or LD, was shown in the SOD treated groups. Conclusions: Early reperfusion resulted in myocardial salvage as assessed by tetrazolium staining and peak ASAT, CK, and LD at 90 min after the reperfusion. No limitation of infarct size by SOD could be demonstrated from analyses of plasma CK, ASAT, or LD.
KEYWORDS myocardial infarction; reperfusion; superoxide dismutase; aspartate aminotransferase; creatine kinase; lactate dehydrogenase; pig
The skilful technical assistance of Ms Agneta Oberg and Ms Ulla Jonsson is greatly appreciated. This study was supported by grants from the Swedish Medical Research Council (grant No B87-14x-07914-02B), the Swedish Natural Science Research Council (grant No 9204). the Foundation for Medical Research at the University of Umei, the Swedish Association for Heart and Lung Patients, and the Swedish Heart and Lung Foundation. Funds for animal purchase and enzymes were kindly supplied by Pharmacia AB, Uppsala, Sweden.
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