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

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.

• Authors: Rosanna Di Paola, Emanuela Mazzon, Irene Paterniti, Daniela Impellizzeri, Placido Bramanti, Salvatore Cuzzocrea
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 650 Issue 2-3 Pg. 612-20 (Jan 15 2011) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 21035441 (Publication Type: Journal Article)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

• Imidazoles
• Interleukin-1beta
• NF-kappa B
• P-Selectin
• Phosphodiesterase 3 Inhibitors
• Pyridones
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• Poly Adenosine Diphosphate Ribose
• olprinone

Topics

• Animals
• Apoptosis (drug effects)
• Imidazoles (pharmacology, therapeutic use)
• Inflammation (metabolism, prevention & control)
• Intercellular Adhesion Molecule-1 (metabolism)
• Interleukin-1beta (metabolism)
• Male
• Myocardial Reperfusion Injury (drug therapy, metabolism, pathology)
• NF-kappa B (metabolism)
• P-Selectin (metabolism)
• Phosphodiesterase 3 Inhibitors (pharmacology, therapeutic use)
• Poly Adenosine Diphosphate Ribose (metabolism)
• Pyridones (pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Tumor Necrosis Factor-alpha (metabolism)