The investigators propose to study the effects of endothelial cell injury on gut hemodynamics in the pathogenesis of necrotizing enterocolitis (NEC). They propose that clinically relevant gut ischemia develops within localized areas of the gut and occurs secondary to antecedent damage to the vascular endothelium which lines the intestinal circulation. Specifically, they submit that endothelial cell damage is an essential part of the early pathogenesis of NEC; this injury attenuates production of endothelium-derived relaxing factor (EDRF), impairs regional perfusion and eventually compromises parenchymal viability. To test this hypothesis, the proposed experiments are designed: (1) to determine if endothelial cell injury attenuates EDRF production by postnatal mesenteric arteries in an age- dependent fashion; (2) to examine if endothelial cell injury alters the pressure-flow relationship within postnatal mesenteric arteries in an age- dependent fashion; (3) to determine if structural injury to endothelial cells occurs in an age-dependent fashion; and (4) to examine if endothelial cell injury alters the response of the intestinal circulation to exogenous constrictor and dilator stimuli in an age- dependent fashion. Endothelial cell injury will be induced by application of ischemia/reperfusion, insofar as this method is reproducible, inexpensive and clinically relevant. Studies will be conducted in 1-, 3- and 35-day old swine, a species which has proven to be an excellent model for the study of developmental physiology. Assessment of the effects of endothelial cell injury on EDRF production will include in vitro techniques, wherein relaxation of precontracted artery rings and production of cGMP are used as markers of EDRF production. Other studies will explore the effects of endothelial cell injury on gut hemodynamics in vivo. The investigators expect that results of this work may implicate endothelial damage in causing significant, age-dependent effects on gut vascular function. If so, they propose that such injury may be common to a number of different """"""""trigger events"""""""" leading to NEC.
| Nowicki, P T (1998) Effects of sustained flow reduction on postnatal intestinal circulation. Am J Physiol 275:G758-68 |
| Nowicki, P T (1998) Postnatal changes in gut hemodynamics: a possible role for substance P. Am J Physiol 274:G1142-50 |
| Nowicki, P T (1996) The effects of ischemia-reperfusion on endothelial cell function in postnatal intestine. Pediatr Res 39:267-74 |
