Olprinone, a PDE3 inhibitor, modulates the inflammation associated with myocardial ischemia-reperfusion injury in rats

Rosanna Di Paola, Emanuela Mazzon, Irene Paterniti, Daniela Impellizzeri, Placido Bramanti, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

Abstract

Coronary ischemia and subsequent reperfusion result in deleterious effects, one of the principal ones being vascular and myocardial inflammation. Olprinone hydrochloride, a specific phosphodiesterase III inhibitor, has anti-inflammatory effects in addition to its inotropic and vasodilator effects. The purpose of this study was to examine the beneficial effects of olprinone on myocardial ischemia-reperfusion injury. Myocardial ischemia-reperfusion injury was caused by clamping the LAD (left anterior descending) coronary artery for 25 min followed by a release of the clamp allowing reperfusion for 1 h. Olprinone i.p. (0.2 mg/kg, i.p.) was administrated 15 min after ischemia. The olprinone administration significantly reduced the: (1) histological evidence of myocardial injury, (2) pro-inflammatory cytokines: tumor necrosis factor-α (TNF-α) and Interleukin-1β (IL-1β), (3) adhesion molecules: Inter-Cellular Adhesion Molecule 1 (ICAM-1) and P-Selectin, (4) nitrotyrosine formation, (5) nuclear factor kappa-B (NF-κB) expression, (6) Poly (ADP-ribose) (PAR) formation, and (7) apoptosis (Bax, Bcl-2, Fas-L and terminal deoxynucleotidyl transferase-mediated UTP end labeling (TUNEL). Based on these findings this study provides the evidence that treatment with olprinone ameliorated the inflammatory process associated with myocardial ischemia-reperfusion in rats and suggests that this drug may have potential in the treatment of various ischemia and reperfusion diseases.

Original languageEnglish
Pages (from-to)612-620
Number of pages9
JournalEuropean Journal of Pharmacology
Volume650
Issue number2-3
DOIs
Publication statusPublished - Jan 15 2011

Keywords

  • Apoptosis
  • Inflammation
  • Myocardial ischemia-reperfusion
  • Olprinone
  • Phosphodiesterase III inhibitor
  • Pro-inflammatory cytokine

ASJC Scopus subject areas

  • Pharmacology

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