Reduction of myocardial reperfusion injury with human soluble complement receptor type 1 (BRL 55730)

• Published in: European journal of pharmacology Vol. 236; no. 3; pp. 477 - 481
• Main Authors: Smith, Edward F., Griswold, Donald E., Egan, John W., Hillegass, Leonard M., Smith, Richard A.G., Hibbs, Martin J., Gagnon, Robert C.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 04.06.1993; Elsevier
• Subjects: Animals; Antianginal agents. Coronary vasodilator agents; Biological and medical sciences; Cardiovascular system; Complement receptors; Disease Models, Animal; Humans; Male; Medical sciences; Myeloperoxidase; Myocardial infarction; Myocardial Infarction - drug therapy; Myocardial Reperfusion Injury - drug therapy; Neutrophils; Neutrophils - drug effects; Neutrophils - physiology; Peroxidase - metabolism; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Receptors, Complement - metabolism; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacokinetics; Recombinant Proteins - therapeutic use; Myocardial infarction; Complement receptors; Myeloperoxidase; Neutrophils; Heart; Human; Animal model; Intravenous administration; Infarct; Rat; Rodentia; Coronary artery; Cardiovascular disease; Coronary heart disease; Left ventricle; Complement C1r; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Treatment; Animal; Blood vessel; Myocardium; Circulatory system; Neutrophil; Pharmacokinetics; Biological receptor
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(93)90487-3

This study was designed to evaluate the cardioprotective effects of a solubilized human complement receptor, sCR1, in the rat subjected to myocardial infarction. Following coronary artery occlusion for 0.5 h and reperfusion for 24 h (MI/R group), myocardial infarct size (determined by planimetric analysis) was 18.3±2.1% of the left ventricle (n = 16), while myeloperoxidase activity (a biochemical marker of neutrophil activation) was increased from 0.94±0.09 U/g tissue in the sham 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 min prior to coronary artery occlusion) produced plasma concentrations of 154±4 μg/ml 1 min prior to coronary artery occlusion, and concentrations of 86±2 and 58±3 μg/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 the MI/R + vehicle group). Administration of sCR1 5 min prior to reperfusion afforded a 25.3% non-significant reduction in myocardial injury. These results a beneficial effect of sCR1 in myocardial ischemia/reperfusion injury by reducing the infiltration of neutrophils and attenuating the extent of myocardial injury.