The goal of this project is to investigate local vascular control of intestinal oxygenation during postnatal development. Metabolic activity within newborn intestine is increased in comparison to fetal or adult gut, as evidenced by the high rate of intestinal oxygen uptake characteristic of this age. The metabolic theory of local blood flow regulation postulates an intimate link between tissue metabolic rate and the efficacy of local control of oxygen transport; this theory thus predicts that the efficacy of local vascular control should be exceptional in newborn gut. Paradoxically, preliminary studies in this laboratory have suggested that newborn intestine is less capable of local control of oxygen transport than intestine from older animals. Accordingly, the working hypothesis of this grant application is as follows: Local control of intestinal oxygen transport is ineffective during early postnatal life; this regulatory mechanism is not capable of maintaining oxygen transport at a rate consistent with the oxidative needs of the tissue. To test this hypothesis, the specific aims of this proposal are: 1. To determine if lowering base-line oxygen uptake affects the relationship between blood flow and oxygen uptake; 2. To quantify autoregulation of intestinal exchange vessels in 1, 3, 7, 14 and 30 day old swine intestine; 3. To determine if lowering base-line intestinal oxygen delivery affects the efficacy of pressure-flow autoregulation in 3 and 30 day old swine intestine; 4. To quantify autoregulatory escape from norepinephrine, vasopressin and angiotensin in intestine from 3 and 30 day old swine intestine; 5. To determine the effects of cardiogenic shock on intestinal hemodynamics and oxygenation in 3 and 30 day old swine intestine; 6. To quantify postprandial hemodynamic events following spontaneous ingestion of an age-appropriate meal in 3, 7, 14 and 30 day old conscious, free-standing swine; 7. To determine the effect of sustained enteral fasting from birth through postnatal day 3 on the efficacy of pressure-flow autoregulation. These experiments will provide novel data regarding the developmental physiology of intestinal oxygen transport, a process vital to postnatal gut adaptation, and thus to survival of the organism.
| Su, Baogen Y; Reber, Kristina M; Nankervis, Craig A et al. (2003) Development of the myogenic response in postnatal intestine: role of PKC. Am J Physiol Gastrointest Liver Physiol 284:G445-52 |
| Reber, Kristina M; Su, Baogen Y; Clark, K Reed et al. (2002) Developmental expression of eNOS in postnatal swine mesenteric artery. Am J Physiol Gastrointest Liver Physiol 283:G1328-35 |
| Reber, Kristina M; Nankervis, Craig A; Nowicki, Philip T (2002) Newborn intestinal circulation. Physiology and pathophysiology. Clin Perinatol 29:23-39 |
| Nankervis, C A; Dunaway, D J; Nowicki, P T (2001) Determinants of terminal mesenteric artery resistance during the first postnatal month. Am J Physiol Gastrointest Liver Physiol 280:G678-86 |
| Reber, K M; Mager, G M; Miller, C E et al. (2001) Relationship between flow rate and NO production in postnatal mesenteric arteries. Am J Physiol Gastrointest Liver Physiol 280:G43-50 |
| Nankervis, C A; Reber, K M; Nowicki, P T (2001) Age-dependent changes in the postnatal intestinal microcirculation. Microcirculation 8:377-87 |
| Nankervis, C A; Nowicki, P T (2000) Role of endothelin-1 in regulation of the postnatal intestinal circulation. Am J Physiol Gastrointest Liver Physiol 278:G367-75 |
| Nowicki, P T (1999) Effects of sustained low-flow perfusion on the response to vasoconstrictor agents in postnatal intestine. Am J Physiol 276:G1408-16 |
| Nowicki, P T; Minnich, L A (1999) Effects of systemic hypotension on postnatal intestinal circulation: role of angiotensin. Am J Physiol 276:G341-52 |
| Nowicki, P T (1998) Effects of sustained flow reduction on postnatal intestinal circulation. Am J Physiol 275:G758-68 |
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