Gastric intramucosal pH and multiple organ injury: impact of ischemia-reperfusion and xanthine oxidase.

OBJECTIVES: To determine if gastric intramucosal pH is affected by hepatoneteric ischemia-reperfusion. We additionally proposed to determine if changes in gastric mucosal hydrogen ion concentration are associated with liver and lung injury following hepatoenteric ischemia-reperfusion. Finally, we hypothesized that gastric intramucosal pH is influenced by xanthine oxidase, an oxidant-generating enzyme released after hepatoenteric ischemia-reperfusion.
DESIGN: Randomized, controlled, animal study.
SETTING: University-based animal research facility.
SUBJECTS: Thirty-six New Zealand white male rabbits (2 to 3 kg).
INTERVENTIONS: Anesthetized rabbits were randomly assigned to one of four groups (n = 9 per group): a) sham-operated group; b) sham-operated group pretreated with sodium tungstate (xanthine oxidase inactivator); c) aorta occlusion group; and d) aorta occlusion group pretreated with sodium tungstate. Descending thoracic aorta occlusion was maintained for 40 mins with a 4-Fr Fogarty embolectomy catheter, followed by 2 hrs of reperfusion.
MEASUREMENTS AND MAIN RESULTS: Gastric tonometry was performed after completion of the surgical preparation (30-min equilibration) and at 30, 60, 90, and 120 mins of reperfusion. Plasma alanine aminotransferase activity was determined at 120 mins of reperfusion to assess hepatic injury. Bronchoalveolar lavage of the right lung was performed after 120 mins of reperfusion, and the protein content was determined as a measure of pulmonary alveolar-capillary membrane compromise. Descending thoracic aorta occlusion resulted in a significant decrease in gastric intramucosal pH as compared with sham-operated rabbits (p < .001). The change in gastric mucosal hydrogen ion concentration was significantly associated with plasma alanine aminotransferase activity (r2 = .48, p < .01) and bronchoalveolar protein content (r2 = .51, p < .01). Xanthine oxidase inactivation significantly improved gastric intramucosal pH after aortic occlusion and reperfusion (p < .001), with a concomitant attenuation of the release of plasma alanine aminotransferase (p < .05) and accumulation of bronchoalveolar protein (p < .05) during reperfusion.
CONCLUSIONS: Gastric intramucosal pH was significantly decreased after hepatoenteric ischemia-reperfusion. Furthermore, an increase in gastric intramucosal hydrogen ion concentration was associated with a concomitant increase in tissue injury, a presumed harbinger of multiple organ failure. Gastric intramucosal pH values improved during reperfusion after xanthine oxidase inactivation, concomitant with attenuation of hepatic and pulmonary injury. Gastric tonometry is an important clinical tool that can provide critical insight into the pathogenesis of multiple organ injury after hepatoenteric ischemia-reperfusion. Gastric tonometry may aid in the rapid assessment of pharmacologic interventions designed to attenuate multiple organ injury in similar clinical settings (e.g., trauma, shock, major vascular surgery).