Lung injury after hepatoenteric ischemia-reperfusion: Role of xanthine oxidase

Vance G. Nielsen, Sidhartha Tan, Abraham Weinbroum, Andrew T. Mccammon, Paul N. Samuelson, Simon Gelman, Dale A. Parks

Research output: Contribution to journalArticle

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Abstract

Oxidant stress plays a major role in the pathophysiologic processes associated with ischemia-reperfusion injury. Xanthine oxidase (XO) is often implicated as a significant source of oxidants and increases in the circulation after hepatoenteric ischemia-reperfusion. We hypothesized that pulmonary injury is associated with hepatic ischemia-reperfusion resulting from descending thoracic aorta occlusion-reperfusion (AoOR). We also proposed that this remote pulmonary injury is attenuated through inactivation of circulating and tissue XO by tungstate, implicating an XO-dependent mechanism. Aortic occlusion was established in rabbits (standard or tungstate diet) for 40 min by 2 h reperfusion. Sham operated rabbits (standard or tungstate diet) served as controls. Hepatic reperfusion injury, as manifested by release of the hepatocellular enzyme alanine aminotransferase (ALT), was markedly increased after AoOR. Suprarenal-intrahepatic occlusion failed to increase ALT release. Tungstate pretreatment significantly (p < 0.05) reduced XO activity and ameliorated liver and intestinal injury (p < 0.05). Lung injury, manifested by increased bronchoalveolar lavage (BAL) protein concentration, BAL lactate dehydrogenase (LDH) activity and increased lung edema was significantly associated with liver injury (p < 0.05) and circulating XO activity (p < 0.001). XO inactivation significantly decreased BAL protein concentration, BAL LDH activity, and lung edema (p < 0.05). We conclude that remote pulmonary injury is significantly influenced by the extent of liver injury and circulating XO activity.

Original languageEnglish (US)
Pages (from-to)1364-1369
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Volume154
Issue number5
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

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ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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