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

Br J Pharmacol. 1999 Nov;128(5):945-52. doi: 10.1038/sj.bjp.0702889.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Cardiovascular Agents / pharmacology*
  • Glycosylation
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Hemodynamics / drug effects
  • Male
  • Monocytes / physiology
  • Myocardial Infarction / pathology*
  • Myocardial Ischemia / pathology
  • Myocardium / cytology
  • Myocardium / metabolism
  • Oligosaccharides / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Complement / chemistry*
  • Recombinant Proteins / pharmacology
  • Sialyl Lewis X Antigen
  • Troponin T / blood

Substances

  • Cardiovascular Agents
  • Oligosaccharides
  • Receptors, Complement
  • Recombinant Proteins
  • Sialyl Lewis X Antigen
  • Troponin T
  • soluble complement inhibitor 1