LUNG INJURY AFTER HEPATOENTERIC ISCHEMIA-REPERFUSION - ROLE OF XANTHINE-OXIDASE

Oxidant stress plays a major role in the pathophysiologic processes as sociated with ischemia-reperfusion injury. Xanthine oxidase (XO) is of ten implicated as a significant source of oxidants and increases in th e circulation after hepatoenteric ischemia-reperfusion. We hypothesize d that pulmonary injury is associated with hepatic ischemia-reperfusio n resulting from descending thoracic aorta occlusion-reperfusion (AoOR ). We also proposed that this remote pulmonary injury is attenuated th rough inactivation of circulating and tissue XO by tungstate, implicat ing an XO-dependent mechanism. Aortic occlusion was established in rab bits (standard or tungstate diet) for 40 min by 2 h reperfusion. Sham operated rabbits (standard or tungstate diet) served as controls. Hepa tic reperfusion injury, as manifested by release of the hepatocellular enzyme alanine aminotransferase (ALT), was markedly increased after A oOR. Suprarenal-infrahepatic occlusion failed to increase ALT release. Tungstate pretreatment significantly (p < 0.05) reduced XO activity a nd ameliorated liver and intestinal injury (p < 0.05). Lung injury, ma nifested by increased bronchoalveolar lavage (BAL) protein concentrati on, BAL lactate dehydrogenase (LDH) activity and increased lung edema was significantly associated with liver injury (p < 0.05) and circulat ing XO activity (p < 0.001). XO inactivation significantly decreased B AL 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.