Reduction of myocardial infarct size with sCR1sLex, an alternatively glycosylated form of human soluble complement receptor type 1 (sCR1), possessing sialyl Lewis x

摘要

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.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.Infusion of sCR1 (1, 5 or 15 mg kg−1, each n=7) or sCR1sLex (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.Infusion of sCR1 (15 mg kg−1, n=5) or sCR1sLex (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.Thus, sCR1 or sCRsLex 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 sCR1sLex are not entirely clear, but may be due complement inhibition and/or prevention of the adhesion and activation of neutrophils.