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Real Time Analysis of Metabolic Profile in Ex Vivo Mouse Intestinal Crypt Organoid Cultures
Published on: November 3, 2014
Transit time heterogeneity in canine small intestine: significance for oxygen transport
H V Connolly1, L A Maginniss, P T Schumacker
1Department of Pediatrics, The University of Chicago, Illinois 60637, USA.
Abstract:
We previously found that local O2 extraction efficacy in isolated pump-perfused intestine was enhanced when systemic reflex vasoconstriction was stimulated by hypovolemia (Samsel, R.W., and P.T. Schumacker. 1994. J. Appl. Physiol. 77: 2291-2298). The microvascular mechanism underlying this beneficial effect could involve a redistribution of flow between mucosa and serosa, or an adjustment in the heterogeneity of perfusion within those regions. We measured regional blood flows and distributions of flow and capillary erythrocyte transit times in two segments of small intestine in anesthetized dogs (n = 10). Each vascularly isolated segment of intestine was pump-perfused under high flow (O2 supply-independent VO2) and low flow (O2 supply-dependent) conditions. During the first gut segment, the animal was kept normovolemic using i.v. fluids to minimize reflex vasoconstriction. During the second, the animal was hemorrhaged to augment vasoconstriction (n = 7), or kept normovolemic to control for the effects of time (n = 3). Blood flow distributions were measured using 15 microm radiolabeled microspheres. Tissue blood volume was measured using 99mTc-labeled red blood cells. Capillary volume was determined as the product of tissue blood volume and the histologically derived fraction of vascular volume in the capillaries. Transit times were calculated as the ratio of capillary volume to flow. Each gut segment was fixed and sectioned into 350 approximately 100 mg tissue pieces for analysis. Data revealed significant spatial heterogeneity of blood flow and capillary transit times in both mucosa and muscularis, with relative dispersions (SD/Mean) ranging from 23 to 97%. Hypovolemia caused an increase in flow heterogeneity in muscularis at both high and low flow states, and in mucosa under high flow conditions. However, hypovolemia also elicited changes in capillary volume, such that transit time heterogeneity remained unchanged. Augmentation of vasoconstrictor tone caused a redistribution of flow toward mucosa (P < 0.003) under high and low flow conditions. This redistribution correlated with the improvements in O2 extraction ratio (P = 0.022). Thus, the improvement in gut O2 extraction efficacy seen with increased vasoconstriction may be explained mostly by an intramural redistribution of flow between mucosa and muscularis. Capillary transit time heterogeneity remained unchanged, suggesting that this variable is tightly regulated.
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