The overall objective of this research proposal is to elucidate the myogenic, neural and hormonal control mechanisms for the control of colonic motor function in health and disease. Particular emphasis is laid on the cyclic motor and myoelectrical activities in the colon, the mechanisms of intiation and propagation of these cyclic activities, the effects of control, low fiber and high fiber diets on these activities, the coupling between colonic electrical and contractile activities, and the effects of some selected pharmacologic agents and peptides on colonic electrical and contractile activities. The experiments will be done on conscious and anesthetized dogs using implanted strain gauges and electrodes and on humans using intraluminal recording tubes mounted with suction cup electrodes and strain gauge elements. The role of nerves in the control of colonic motility will be studied by the techniques of nerve section and electrical stimulation of nerves. The coupling between electrical and contractile activities and the effect of pharmacological agents will be studied by close intraarterial perfusions and systemic administrations. The data will be analysed by computer and/or electronic filtering and visually. Our long term goal is to apply the knowledge and understanding obtained from animal experiments to the study of human colonic motor function in health and in various pathological states such as irritable bowel syndrome, idiopathic intestinal pseudoobstruction, and diverticular disease. An insight into the functioning of the myogenic, neural and hormonal control mechanisms in health and in colonic motility disorders will be essential to propose appropriate pharmacological, therapeutical and surgical measures to normalize colonic motor function in disease.
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