There are several pathological states which are treated, in part, by removal or bypass of a large portion of the small intestine. Removal of a portion of the intestine disturbs the normal physiological state in that profuse diarrhea can develop. In most cases, however, the diarrhea is limited since the remaining intestine adapts so that nutritional compensation becomes adequate. The long term objectives of this proposal are to describe the changes that take place in intestinal smooth muscle during the period of adaptation and to determine possible mechanisms responsible for the changes. Three hypotheses are to be tested: 1) intestinal bypass induces changes in the physical and biochemical functions and in the structure of intestinal smooth muscle, 2) the changes in intestinal smooth muscle are in part responsible for the overall adaptation, and 3) these changes in function and structure of the muscle are induced by local factors such as changes in luminal bulk and/or by systemic factors such as gastrointestinal hormones. Small bowel bypass will be performed in rats. Physiological, anatomical, and biochemical parameters of intestinal smooth muscle will be evaluated at various times after operation in both the bypassed and in-continuity segments of bowel. Function in vivo will be assessed by determining intestinal transit times and the patterns of myoelectrical activity. Function in vitro will be assessed by determining the force of isometric contractions of muscle strips taken from the intestine. Anatomical changes will be assessed by determining the areas of the muscle layers and the sizes of individual muscle cells. Biochemically, the muscle will be assessed by determining its contents of total protein, contractile proteins, and collagen. Additionally, mitochondrial activity and the relationship between contractile activity and the phosphorylation of the 20,000 dalton light chains of myosin will be assessed. Mechanisms responsible for any adaptations will be investigated by following selected properties of the intestinal smooth muscle while varying the contents of the intestine, the hormonal and/or neural state of the animals and by comparing changes noted in selected properties after bypass to changes that occur after infection of control aminals with Trichinella spirallis, a parasite which also causes changes in structure and function of intestinal smooth muscle.
