Functional Heterogeneity in the Gut: Relevance to Oxygen Transport and the Maintenance of Oxygen Consumption
The oxygen supply to tissue microvascular units normally exceeds oxygen demand. Under these conditions, cell respiration is set by metabolic activity rather than by O2 supply. As tissue oxygen delivery is reduced, increases in tissue oxygen extraction are optimized if blood flow among microvascular units is redistributed in proportion to oxygen demand. This redistribution is crucial for the maintenance of cell respiration in tissues with regional heterogeneity in metabolic activity. Heterogeneous tissues that fail to optimally redistribute blood flow during reductions in oxygen supply are more liable to sustain hypoxic tissue injury, because poorly perfused units with high metabolic demands may become O2 supply-dependent while other units are relatively well perfused. The role of reflex sympathetic vasoconstrictor tone in this redistribution was investigated in vascularly isolated segments of canine small intestine perfused with an occlusive roller pump. Dogs were anesthetized and ventilated with room air. Oxygen delivery to the innervated gut segment was reduced in stages by lowering the speed of the pump. In a normovolemic group, systemic sympathetic tone was minimized during this procedure by intravenous fluid administration. In a hypovolemic group, sympathetic tone was augmented by controlled hemorrhage. The onset of O2 supply-dependent metabolism in the gut was determined in each experiment from analysis of O2 delivery-uptake data. Gut critical oxygen extraction in the normovolemic group (45.6±11.5%) was significantly poorer than for the hypovolemic group (68.4±3.4%). Gut vascular resistance was significantly higher at the critical point in the hypovolemic group. These results suggest that reflex sympathetic vasoconstriction contributes to the increases in gut extraction during progressive ischemia. To clarify the source of this vasoconstrictor tone, a-adrenergic vasoconstriction was inhibited with phenoxybenzamine (3 mg/kg) in another hypovolemic group. Gut critical oxygen extraction after phenoxybenzamine was not less (p=n.s.) than the hypovolemic group. Moreover, phenoxybenzamine did not abolish the progressive increases in gut vascular resistance in response to systemic hypovolemia. These results suggest that non-adrenergic reflex vasoconstriction in the gut mediates the increase in vascular tone, which contributes to the flow redistribution during progressive ischemia. Interestingly, if systemic hemorrhage was initiated in a normovolemic group while the gut was in the middle of the supply-dependent range, progressive increases in gut O2 extraction were observed at constant gut O2 delivery. Collectively, these results may reflect a more efficient partitioning of blood flow between mucosa and muscularis, which are characterized by different intrinsic metabolic activities. However, reflex sympathetic vasoconstriction may also act within each of these regions to reduce functional heterogeneity by limiting perfusion to units with low metabolic needs. Conceivably, sympathetic vasoconstriction may also alter perfused capillary surface area in the gut, where capillary recruitment may be actively regulated via pre-capillary sphincters. In either case, these results demonstrate that efficient microvascular regulation in the gut requires extrinsic neural control which is non-adrenergic. In the absence of such tone, local metabolic vasodilation remains intact, but is inadequate to achieve high critical oxygen extractions.