Effects of Nonischemic Hypoxia on Jejunal Mucosal Structure and Function: Study of an Experimental Model in Dogs

ABSTRACT: A model of nonischemic hypoxia of the jejunum was designed in dogs, by shunting of blood from the inferior vena cava directly into the regional mesenteric arterial supply, thereby lowering the PaO₂ of the blood that reached the jejunal wall from 98.6 ± 3 to 62 ± 5 mm Hg. Absorption rates of sodium, glucose, fructose, glycine, and the dibasic aminoacid lysine were studied by in situ luminal perfusion of a 30-cm proximal jejunal segment with a bicarbonate buffer solution containing phenol red as a nonabsorbable marker for determination of water fluxes. During periods of control, hypoxia, and after discontinuation of the venoarterial admixture (recovery), effluent perfusate was collected and mucosal biopsies were obtained for assay of lactase, maltase and sucrase activity, mucosal ATPase activity and ATP content, and for light- and electron microscopic examination. Mesenteric supply with hypoxic blood was associated with a significant inhibition of Na⁺,K⁺-ATPase activity (p<0.001) and a rise in mucosal ATP content (p<0.05). There was a significant reduction in the absorption rates of sodium (p<0.001), glucose, and glycine (p<0.01), but no change in the transport of fructose and of lysine. Brush border enzymes were unaltered. The histological appearance of the mucosa remained normal throughout the experiment, but on electron microscopy a distinct swelling of the enterocyte mitochondria was noted during the hypoxia period. Discontinuation of the venoarterial shunt and return to well-oxygenated mesenteric blood supply to the small gut was associated with a recuperation of Na⁺, K⁺-ATPase activity, decrease of mucosal ATP content, improvement of mucosal absorption capacity, and disappearance of the mitochondrial swelling. It is concluded that nonischemic hypoxia of the jejunum can impair Na⁺, -K⁺-ATPase-related jejunal absorption functions in the absence of apparent structural damage.