Olprinone Attenuates the Development of Ischemia/reperfusion Injury of the Gut

Overview

Journal Intensive Care Med

Specialty Critical Care

Date 2010 Mar 30

PMID 20349038

Citations 7

Authors

Concetta Crisafulli

Emanuela Mazzon

Maria Galuppo

Irene Paterniti

Rocco Caminiti

Salvatore Cuzzocrea

Affiliations

Soon will be listed here.

Abstract

Purpose: Splanchnic artery occlusion (SAO) shock is a severe form of circulatory shock produced by ischemia and reperfusion of the splanchnic organs. The occlusion and reperfusion of the splanchnic arteries causes activation and adhesion of polymorphonuclear neutrophils (PMNs), release of proinflammatory substances and the formation of both species of oxygen and nitrogen derivatives free radicals. Olprinone is a specific phosphodiesterase-III inhibitor that has many properties; one of which is anti-inflammatory actions at therapeutic concentrations clinically used for heart failure. In this study, we wanted to evaluate the pharmacological action of olprinone (a PDEIII inhibitor) on SAO shock in mice.

Methods: SAO shock was induced by clamping both the superior mesenteric artery and the celiac trunk, resulting in a total occlusion of these arteries for 30 min. After this period of occlusion, the clamps were removed. Olprinone was given at a dose of 0.2 mg/kg i.p. 15 min before reperfusion.

Results: Our results indicated that olprinone up-regulated cAMP in injured ileum tissue, and decreased the ileum tissue damage after 1 h of reperfusion in SAO shock mice. Moreover, olprinone decreased NF-kappaB expression; the nitration of tyrosine residues; the phosphorylation of p38 MAPK and JNK; cytokine production (TNF-alpha and IL-1beta); ICAM-1 and P-selectin expression and apoptosis in the injured ileum.

Conclusions: These results could imply a future use of olprinone in the therapy of ischemia and reperfusion shock.

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