Pathomorphological manifestations of ischemic involvement of the small intestine in acute occlusion of the mesenteric artery

Relevance. Lethality rates (63-95%) among patients with acute intestinal ischemia remain consistently high during the last decades. Despite the high urgency of the problem and numerous works devoted to visualization, early laboratory and instrumental diagnostics of ischemic bowel disease, clinical results have not changed significantly during the last 15-20 years. Pathogenetic mechanisms of various variants of ischemic intestinal lesion and their pathomorphological manifestations should become the basis for the development of surgical tactics and require specification. The aim is to study pathomorphological manifestations and to clarify on their basis the pathogenetic mechanisms of ischemic involvement of the small intestine in acute occlusion of the mesenteric artery in the experiment. Materials and methods. An experimental study was performed on 10 laboratory animals - male rats of the Wistar line. Modeling acute mesenteric ischemia was carried out via dressing of the jejunal artery. The ischemic intestine was collected for a stepwise histological study, the morphometry of the layers of the intestinal wall and the prevalence of necrosis. Results. At the time of the appearance of macroscopic signs of lack of vitality in the central sector of the ischemic intestine, the wall thickness was 47.6% less than normal and in the adjacent peripheral sectors by 40.6%. Thinning of the intestinal wall was due to alteration of the mucosa with a decrease in its share in the total wall thickness from 86 to 82% (p = 0.021) in all sectors. The share of area occupied by necrosis in groups "B" and "C" was not statistically significant (p = 0.872) and amounted to 17.1 [7.3; 64.9]%. The state of the intramural vessels of the intestinal wall had significantly changed in comparison with the intact intestine. Signs of hypoperfusion in the form of sludge in the microvessels of the mucous membrane and the submucosa had been revealed. Conclusions. Pathomorphological manifestations of ischemic bowel disease in acute occlusive mesenteric ischemia resulted in a decrease in the total thickness of the wall and a change in the ratio of serous-muscular and mucosal-submucosal layers due to a decrease in the proportion of the latter. The severity of necrosis in the central and peripheral parts of the ischemic intestine did not differ.

Leukocyte adherence to venular endothelium during ischemia-reperfusion

Xanthine oxidase-derived oxidants and leukocytes have been implicated in the microvascular injury associated with reperfusion of ischemic intestine. The objective of this study was to determine whether xanthine oxidase-derived oxidants play a role in the leukocyte-microvascular interactions initiated by ischemia-reperfusion. Adherence and extravasation of leukocytes were monitored in cat mesenteric venules subjected to 1 h of ischemia (blood flow reduced to 20% of control) and reperfusion. Leukocyte rolling velocity, vessel diameter, and red cell velocity were also measured in control (untreated) animals and in animals pretreated with either allopurinol or superoxide dismutase. The responses of venular blood flow, wall shear rate, and leukocyte rolling velocity to ischemia and reperfusion did not differ between the three experimental groups. In control animals, 1 h of ischemia was associated with significant adherence and extravasation of leukocytes with reperfusion greatly enhancing these responses. Allopurinol treatment did not alter the responses to ischemia per se, yet it largely prevented the further increment in adherence and extravasation associated with reperfusion. Superoxide dismutase treatment attenuated the leukocyte responses elicited by both ischemia and reperfusion. Our observations that both allopurinol and superoxide dismutase attenuate reperfusion-induced leukocyte adherence and extravasation are consistent with the hypothesis that xanthine oxidase-derived oxidants initiate the leukocyte infiltration induced by reperfusion of ischemic intestine.

Conversion of xanthine dehydrogenase to oxidase in ischemic rat intestine: a reevaluation

Oxygen radicals derived from xanthine oxidase (XO) are important mediators of the cellular injury associated with reperfusion of ischemic intestine, stomach, liver, kidney, and pancreas. XO exists in nonischemic tissue predominantly as xanthine dehydrogenase (XDH) and converts to oxygen radical-producing XO with ischemia. Grinding intestine under liquid nitrogen and placing the powder in phosphate buffer (pH 7.0) containing thiol reductants and protease inhibitors adequately preserved total XDH + XO activity and the percentage in the oxidase form (%XO) for 24 h. Total activity in nonischemic intestine ranged from 374 nmol.min-1.g-1 in duodenum to 138 nmol.min-1.g-1 in ileum, while XO activity was approximately 19% of total activity throughout the entire small intestine. The rate of XDH conversion to XO during normothermic ischemia varied only slightly throughout the intestine, increasing 13% per hour to 34, 46, and 61% XO after 1, 2, and 3 h of ischemia, respectively. Our results contrast with previous reports where XDH conversion to XO occurred within 60 s ischemia but are consistent with physiological and morphological evidence of ischemic injury and provide further support for involvement of XO in intestinal injury associated with ischemia.