Carbon monoxide inhalation protects rat intestinal grafts from ischemia/reperfusion injury. Academic Article uri icon

Overview

MeSH

  • Administration, Inhalation
  • Animals
  • Antigens, CD31
  • Blood Vessels
  • Carboxyhemoglobin
  • Corrosion Casting
  • Cytokines
  • Enzyme Inhibitors
  • Gases
  • Guanylate Cyclase
  • Inflammation Mediators
  • Male
  • Osmolar Concentration
  • Oxadiazoles
  • Plasminogen Activator Inhibitor 1
  • Quinoxalines
  • RNA, Messenger
  • Rats
  • Rats, Inbred Lew
  • Regional Blood Flow
  • Survival Analysis

MeSH Major

  • Carbon Monoxide
  • Intestine, Small
  • Ischemia
  • Reperfusion Injury

abstract

  • Carbon monoxide (CO), a byproduct of heme catalysis by heme oxygenases, has been shown to exert anti-inflammatory effects. This study examines the cytoprotective efficacy of inhaled CO during intestinal cold ischemia/reperfusion injury associated with small intestinal transplantation. Orthotopic syngenic intestinal transplantation was performed in Lewis rats after 6 hours of cold preservation in University of Wisconsin solution. Three groups were examined: normal untreated controls, control intestinal transplant recipients kept in room air, and recipients exposed to CO (250 ppm) for 1 hour before and 24 hours after surgery. In air grafts, mRNA levels for interleukin-6, cyclooxygenase-2, intracellular adhesion molecule (ICAM-1), and inducible nitric oxide synthase rapidly increased after intestinal transplant. Histopathological analysis revealed severe mucosal erosion, villous congestion, and inflammatory infiltrates. CO effectively blocked an early up-regulation of these mediators, showed less severe histopathological changes, and resulted in significantly improved animal survival of 92% from 58% in air-treated controls. CO also significantly reduced mRNA for proapoptotic Bax, while it up-regulated anti-apoptotic Bcl-2. These changes in CO-treated grafts correlated with well-preserved CD31(+) vascular endothelial cells, less frequent apoptosis/necrosis in intestinal epithelial and capillary endothelial cells, and improved graft tissue blood circulation. Protective effects of CO in this study were mediated via soluble guanylyl cyclase, because 1H-(1,2,4)oxadiazole (4,3-alpha) quinoxaline-1-one (soluble guanylyl cyclase inhibitor) completely reversed the beneficial effect conferred by CO. Perioperative CO inhalation at a low concentration resulted in protection against ischemia/reperfusion injury to intestinal grafts with prolonged cold preservation.

publication date

  • October 2003

has subject area

  • Administration, Inhalation
  • Animals
  • Antigens, CD31
  • Blood Vessels
  • Carbon Monoxide
  • Carboxyhemoglobin
  • Corrosion Casting
  • Cytokines
  • Enzyme Inhibitors
  • Gases
  • Guanylate Cyclase
  • Inflammation Mediators
  • Intestine, Small
  • Ischemia
  • Male
  • Osmolar Concentration
  • Oxadiazoles
  • Plasminogen Activator Inhibitor 1
  • Quinoxalines
  • RNA, Messenger
  • Rats
  • Rats, Inbred Lew
  • Regional Blood Flow
  • Reperfusion Injury
  • Survival Analysis

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1868280

Digital Object Identifier (DOI)

  • 10.1016/S0002-9440(10)63515-8

PubMed ID

  • 14507665

Additional Document Info

start page

  • 1587

end page

  • 1598

volume

  • 163

number

  • 4