Endothelial protection by defibrotide - A new strategy for treatment of myocardial infarction?

K. Schror, G. Ackermann, Th Hohlfeld, P. Lobel, P. Ney, H. Schroder, H. Strobach

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30 Scopus citations

Abstract

Myocardial ischemia is associated with endothelial injury and an apparently insufficient generation of endothelium-derived vasodilating and platelet and white cell inhibitory mediators, such as prostacyclin (PGI2) and EDRF. This paper reviews some recent findings of our laboratory on cardioprotective effects of defibrotide, a PGI2 stimulating agent, in experimental myocardial ischemia and its possible sites of action in several in vitro assay systems. Defibrotide (32 mg/kg x h) reduced the infarct size by 50% in pigs subjected to 1 h of coronary artery ligation followed by 3 h of reperfusion. This was associated with significant inhibition of neutrophil activation during the reperfusion period and a two-to threefold increase in cardiocoronary PGI2 generation. In vitro studies on PAF- and calcium ionophore-stimulated human granulocytes confirmed a dose-dependent (10-1000 μg/ml) antineutrophil effect of defibrotide (inhibition of lysosomal enzyme release) which was independent of the type of stimulus. Defibrotide (0.1 mg/ml) also inhibited superoxide anion generation from PAF stimulated neutrophils in Langendorff-perfused guinea pig hearts and was equipotent to a specific PAF antagonist (BN 52021). Defibrotide (0.1 mg/ml) did not stimulate PGI2 release from cultured porcine aortic endothelial cells but enhanced PGI2 release four-to fivefold above control if endothelial cells were coincubated with platelets. These data demonstrate a considerable cardioprotective potential of defibrotide which appears to involve endothelial protection from granulocyte-derived noxious compounds and a long-lasting stimulation of PGI2 production.

Original languageEnglish (US)
Pages (from-to)35-41
Number of pages7
JournalZeitschrift fur Kardiologie
Volume78
Issue numberSUPPL. 6
StatePublished - Jan 1 1989

Keywords

  • Defibrotide
  • Endothelial cells
  • Myocardial ischemia
  • Neutrophils
  • Platelet
  • Prostacyclin
  • Thromboxane

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    Schror, K., Ackermann, G., Hohlfeld, T., Lobel, P., Ney, P., Schroder, H., & Strobach, H. (1989). Endothelial protection by defibrotide - A new strategy for treatment of myocardial infarction? Zeitschrift fur Kardiologie, 78(SUPPL. 6), 35-41.