Reduction of myocardial infarct size with sCR1sLe x , an alternatively glycosylated form of human soluble complement receptor type 1 (sCR1), possessing sialyl Lewis x

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. 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 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. 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. 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.British Journal of Pharmacology (1999) 128 , 945–952; doi: 10.1038/sj.bjp.0702889