Changes in blood flow to the intestine occur in both normal and pathological states (e.g., digestion, exercise, shock, cholera, etc.), and intestinal blood flow has been studied in these states. Yet, the paramount function of the circulation--that of delivering oxygen to the tissue--has not been studied systematically in the intestine. Furthermore, because there is increasing evidence that gut ischemia plays a role in a broad spectrum of diseases, it is imperative that we understand the mechanisms regulating the delivery of oxygen to intestinal tissue. In acute conditions, two means are available for regulating the delivery of oxygen to tissues: (1) changes in blood flow produced by altering vascular resistance, and (2) changes in the diffusion parameters (capillary surface area and diffusion distance) brought about by precapillary sphincter activity. Both vascular resistance and precapillary sphincter activity are under the control of local mechanisms within the intestine itself. In the proposed experiments we will test the metabolic and myogenic theories of autoregulation and study the intestine's ability to regulate its oxygenation. We hope to be able to distinguish capillary surface area changes from permeability changes by using the dual-indicator dilution techniques, to detect the existence of """"""""counter-current"""""""" mechanisms in the intestinal villus by using the new x-ray probe technique, and to determine whether adenosine plays a role as the """"""""metabolic vasodilator."""""""" Finally, because the advance of our knowledge of the physiology and pathophysiology of the intestinal circulation is now impeded by the lack of methods to fractionate the intra-mural distribution of blood flow continuously, we will continue our work on measuring blood flow in the muscularis and in the mucosa of the intestine by using laser Doppler spectroscopy.
