Olprinone attenuates the development of ischemia/reperfusion injury of the gut

Concetta Crisafulli, Emanuela Mazzon, Maria Galuppo, Irene Paterniti, Rocco Caminiti, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

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-κB expression; the nitration of tyrosine residues; the phosphorylation of p38 MAPK and JNK; cytokine production (TNF-α and IL-1β); 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.

Original languageEnglish
Pages (from-to)1235-1247
Number of pages13
JournalIntensive Care Medicine
Volume36
Issue number7
DOIs
Publication statusPublished - Jul 2010

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Keywords

  • Adhesion molecules
  • Apoptosis
  • CaMP
  • Oxygen-free radicals
  • Splanchnic artery occlusion

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Medicine(all)

Cite this

Crisafulli, C., Mazzon, E., Galuppo, M., Paterniti, I., Caminiti, R., & Cuzzocrea, S. (2010). Olprinone attenuates the development of ischemia/reperfusion injury of the gut. Intensive Care Medicine, 36(7), 1235-1247. https://doi.org/10.1007/s00134-010-1798-4