REDUCTION OF MYOCARDIAL REPERFUSION INJURY WITH HUMAN SOLUBLE COMPLEMENT RECEPTOR TYPE-1 (BRL-55730)

This study was designed to evaluate the cardioprotective effects of a solubilized human complement receptor, sCR1, in the rat subjected to m yocardial infarction. Following coronary artery occlusion for 0.5 h an d reperfusion for 24 h (MI/R group), myocardial infarct size (determin ed by planimetric analysis) was 18.3 +/- 2.1% of the left ventricle (n = 16), while myeloperoxidase activity (a biochemical marker of neutro phil activation) was increased from 0.94 +/- 0.09 U/g tissue in the sh am occluded + vehicle group to 2.96 +/- 0.17 U/g tissue in the MI/R vehicle treated group (P < 0.01). Injection of sCR1 (5 mg/kg i.v., 5 m in prior to coronary artery occlusion) produced plasma concentrations of 154 +/- 4 mug/ml 1 min prior to coronary artery occlusion, and conc entrations of 86 +/- 2 and 58 +/- 3 mug/ml at 40 min and 125 min after dosing (n = 6). sCR1 reduced myocardial infarct size to 11.3 +/- 2.2% of the left ventricle, and attenuated the increase in myeloperoxidase activity to 2.11 +/- 0.20 U/g tissue (n = 18; P < 0.01, compared to t he MI/R +/- vehicle group). Administration of sCR1 5 min prior to repe rfusion afforded a 25.3% non-significant reduction in myocardial injur y. These results suggest a beneficial effect of sCR1 in myocardial isc hemia/reperfusion injury by reducing the infiltration of neutrophils a nd attenuating the extent of myocardial injury.