title: Reduction of myocardial infarct size with sCR1sLe(x), an alternatively glycosylated form of human soluble complement receptor type 1 (sCR1), possessing sialyl Lewis x.
abstract: 1 This study investigated the effects of soluble complement receptor type 1 (sCR1) or sCR1sLex, agents which function as a complement inhibitor or as a combined complement inhibitor and selectin adhesion molecule antagonist, respectively, on the infarct size and cardiac troponin T (cTnT) release caused by regional myocardial ischaemia and reperfusion in the rat. 2 Eighty-two, male Wistar rats were subjected to 30 min occlusion of the left anterior descending coronary artery (LAD) followed by 2 h of reperfusion. Haemodynamic parameters were continuously recorded and at the end of the experiments infarct size (with p-nitro-blue tetrazolium) and cTnT release were determined. 3 Infusion of sCR1 (1, 5 or 15 mg kg-1, each n=7) or sCR1sLe(x) (1, 5 or 15 mg kg-1, n=7, 13 or 13, respectively) 5 min prior to LAD-reperfusion caused a reduction in infarct size from 59+/-2% (PBS - control, n=12) to 46+/-6%, 25+/-9% and 37+/-6% or 42+/-6%, 35+/-6% and 35+/-4%, respectively. 4 Infusion of sCR1 (15 mg kg-1, n=5) or sCR1sLe(x) (15 mg kg-1, n=5) also reduces the myocardial TnT release from 80+/-20 ng ml-1 (control) to 13+/-7 or 4+/-1 ng ml-1, respectively. 5 Thus, sCR1 or sCRsLe(x) significantly reduce infarct size and cardiac TnT release caused by 30 min of regional myocardial ischaemia and 2 h of reperfusion in the rat. The mechanisms of the cardioprotective effects of sCR1 or sCR1sLe(x) are not entirely clear, but may be due complement inhibition and/or prevention of the adhesion and activation of neutrophils.
authors.affiliation: The William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Charterhouse Square, London EC1M 6BQ, U.K.
authors.forename: K
authors.initials: K
authors.lastname: Zacharowski
authors.forename: M
authors.initials: M
authors.lastname: Otto
authors.forename: G
authors.initials: G
authors.lastname: Hafner
authors.forename: H C
authors.initials: HC
authors.lastname: Marsh
authors.forename: C
authors.initials: C
authors.lastname: Thiemermann
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D006031:Glycosylation; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009000:Monocytes / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology*; D017202:Myocardial Ischemia / Q000473:pathology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009844:Oligosaccharides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011951:Receptors, Complement / Q000737:chemistry*; D011994:Recombinant Proteins / Q000494:pharmacology; D000080506:Sialyl Lewis X Antigen; D020107:Troponin T / Q000097:blood
chemical_list: D002317:Cardiovascular Agents; D009844:Oligosaccharides; D011951:Receptors, Complement; D011994:Recombinant Proteins; D000080506:Sialyl Lewis X Antigen; D020107:Troponin T; C082885:soluble complement inhibitor 1