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 sCR1sLe(x), 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.