Defibrotide, an antithrombotic substance which prevents myocardial contracture in ischemic rabbit heart

Ferruccio Berti, Giuseppe Rossoni, Claudio Omini, Giancarlo Folco, Luisa Daffonchio, Teresa Viganó, Claudio Tondo

Research output: Contribution to journalArticle

Abstract

Defibrotide, a polydeoxyribonucleotide obtained from mammalian lungs, reduced in a dose-dependent fashion the ischemic contracture due to low perfusion (0.2 ml/min) of isovolumic left heart of rabbit and abolished the irregular rhytym of the heart, thereby restoring the cardiomechanical activity upon reperfusion (20 ml/min). Defibrotide stimulated the release of PG-like material from the heart in a dose-dependent manner without modifying the basal contractility. Both PGE2 and PGI2 (10 ng/ml) have an antiischemic activity on this preparation as shown by the partial reduction of the ischemic contracture and by the improvement of heart contractility upon reperfusion. Indomethacin infusion (1 μg/ml) completely removed both the antiischemic activity of Defibrotide (400 μg/ml) and its ability to increase the generation of prostaglandins in the rabbit heart. These results suggest that Defibrotide has a beneficial influence on ischemic rabbit heart through an increase in prostaglandin synthesis. However other mechanisms not necessarily related to prostaglandin generation, such as direct effect on membrane function deactivation and mitochondrial Ca2+ overload, should be considered in explaining the antiischemic activity of Defibrotide in the rabbit heart.

Original languageEnglish
Pages (from-to)375-382
Number of pages8
JournalEuropean Journal of Pharmacology
Volume135
Issue number3
DOIs
Publication statusPublished - Mar 31 1987

Keywords

  • Defibrotide
  • Indomethacin
  • Myocardial ischemia
  • Prostaglandins

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

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