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 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 microgram/ml 1 min prior to coronary artery occlusion, and concentrations of 86 +/- 2 and 58 +/- 3 micrograms/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 suggest a beneficial effect of sCR1 in myocardial ischemia/reperfusion injury by reducing the infiltration of neutrophils and attenuating the extent of myocardial injury.
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA.
E F
EF
Smith
D E
DE
Griswold
J W
JW
Egan
L M
LM
Hillegass
R A
RA
Smith
M J
MJ
Hibbs
R C
RC
Gagnon
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011951:Receptors, Complement / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use
D011951:Receptors, Complement; D011994:Recombinant Proteins; C082885:soluble complement inhibitor 1; D009195:Peroxidase