Prevention of cardiac cell injury during acute myocardial infarction: possible role for complement inhibition

Am J Cardiovasc Drugs. 2003;3(4):245-51. doi: 10.2165/00129784-200303040-00003.

Abstract

The purpose of this article is to describe mechanisms of cell death in patients with acute myocardial infarction, particularly the activation of the complement system. Various pro-inflammatory cytokines, released by the inflamed tissue, play a role in the activation of the complement system. Several complement inhibitors have been developed to reduce tissue damage following ischemia. According to animal studies the deleterious effects of activators of the complement system can be diminished by complement inhibition. Several clinical studies have been conducted for the potential treatment of cell injury during acute myocardial infarction. C1 inhibitor dose-dependently inhibited complement activation and appeared to reduce myocardial injury after reperfusion therapy in patients with acute myocardial infarction. C1 inhibitor dose-dependently reduced plasma levels of C4 activation fragments. In addition, cardiac enzymes (troponin T and creatine kinase-MB) returned to baseline levels more rapidly among patients treated with C1 inhibitor, compared with controls. Furthermore, preliminary results from a placebo-controlled trial indicate that treatment with intravenous pexelizumab (anti-C5 antibody) was well tolerated in a large number of patients undergoing coronary artery bypass graft surgery. Further, more randomized trials are necessary to clarify the clinical significance of this new and innovative treatment with complement inhibition.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Cell Death
  • Clinical Trials as Topic
  • Complement Activation / drug effects
  • Complement C1 Inactivator Proteins
  • Complement C1 Inhibitor Protein
  • Complement C5 / antagonists & inhibitors
  • Complement C5 / immunology
  • Fibrinolytic Agents / therapeutic use
  • Humans
  • Myocardial Infarction / complications
  • Myocardial Infarction / pathology*
  • Myocardial Infarction / therapy
  • Myocardial Reperfusion Injury / etiology
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Serpins / therapeutic use
  • Single-Chain Antibodies

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Complement C1 Inactivator Proteins
  • Complement C1 Inhibitor Protein
  • Complement C5
  • Fibrinolytic Agents
  • SERPING1 protein, human
  • Serpins
  • Single-Chain Antibodies
  • pexelizumab