Reviparin-sodium prevents complement-mediated myocardial injury in the isolated rabbit heart

J Cardiovasc Pharmacol. 1997 Nov;30(5):658-66. doi: 10.1097/00005344-199711000-00017.

Abstract

The cytoprotective action of reviparin-sodium (LU-47311: Clivarin), a low-molecular-weight heparin, was examined in an ex vivo model of complement-mediated myocardial injury. The effective concentration of reviparin was determined by using an in vitro rabbit erythrocyte-lysis assay using 4% normal human plasma. Reviparin (0.01-2.73 mg/ml) reduced erythrocyte lysis in a concentration-dependent manner. Subsequently, 0.91 mg/ml of reviparin was evaluated in an ex vivo rabbit isolated-heart model of human complement-mediated injury. Hearts perfused in the presence of 0.91 mg/ml of reviparin (n = 10) demonstrated significant preservation of ventricular function compared with vehicle-treated hearts (n = 10), as evidenced by coronary artery perfusion pressure, left ventricular developed pressure, and left ventricular end-diastolic pressure. A reduction in myocyte creatine kinase release was observed in reviparin-treated hearts compared with controls. Myocardial injury in vehicle-treated hearts was associated with an increased assembly of the membrane-attack complex, as determined by immunohistochemical localization of C5b-9 neoantigen. Reviparin decreased fluid-phase Bb formation detected in the lymphatic drainage of plasma-perfused hearts. The results of this study demonstrate that reviparin inhibits complement-mediated myocardial injury as assessed in an ex vivo experimental model of complement activation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anticoagulants / pharmacology*
  • Cardiomyopathies / drug therapy
  • Complement Activation / drug effects*
  • Complement C3 Convertase, Alternative Pathway
  • Complement C3b / metabolism
  • Complement Membrane Attack Complex / analysis*
  • Complement Membrane Attack Complex / antagonists & inhibitors
  • Creatine Kinase / metabolism
  • Fibrinolytic Agents / pharmacology*
  • Heart / drug effects*
  • Heparin, Low-Molecular-Weight / pharmacology*
  • Humans
  • Immunoenzyme Techniques
  • Immunohistochemistry
  • In Vitro Techniques
  • Myocardium / enzymology
  • Myocardium / immunology
  • Myocardium / pathology*
  • Peptide Fragments / metabolism
  • Rabbits

Substances

  • Anticoagulants
  • Complement Membrane Attack Complex
  • Fibrinolytic Agents
  • Heparin, Low-Molecular-Weight
  • Peptide Fragments
  • reviparin
  • Complement C3b
  • Creatine Kinase
  • Complement C3 Convertase, Alternative Pathway