Disordered colonic motility may play an important role in the pathophysiology of many disease states.
The aims of the proposed study are to elucidate the physiology and regulation of colonic transit in an animal model, the cat, and to compare colonic transit in the cat to man. Transit of normal fecal material through different regions of the cat colon will be quantitated using colonic scintigraphy. After implantation of a cecostomy tube, an aliquot of In-111-DTPA will be instilled in order to label the endogenous ileal effluent. Sequential scintigrams will be obtained and the activity in each region quantitated. Colonic transit may be described in various ways: emptying time of a region, regional fecal retention, progression of the geometric mean and time distribution analysis. Electromyographic (EMG) recordings from serosal electrodes will be acquired simultaneously. EMG data will be converted to digital form and analyzed using the Fast Fourier Transform and spike activity analysis. The electrophysiological events will be correlated with the motor activity on a region by region basis. The effects of dietary fiber and meal composition will be studied. Neural influences will be evaluated by administering cholinergic, adrenergic and enkephalinergic agonists and antagonists. Prokinetic agents and gastrointestinal polypeptides such as secretin, gastrin, glucagon, cholecystokinin and somatostatin, which have been demonstrated to influence motility, will be tested. Electrical stimulation will be applied to the serosal electrodes in an attempt to either increase or inhibit slow wave activity. The effects of electrical stimulation on colonic transit will be tested using scintigraphy. Upon completion of the cat studies, preliminary investigations will be performed in man to characterize human colonic physiology. Using an orally introduced catheter, advanced to the cedum, an 8 ml solution of In-111-DTPA will be instilled. Sequential colonic scintigrams will be obtained for 48 hours, and the images will be divided into regions of interest for analysis. This technique is analagous to that employed in cats. Therefore, correlates to the more detailed animal studies may be made. Anticipated areas of study include the effects of meal composition, gastrointestinal polypeptides and prokinetic agents on colonic motility. Neural stimulatory and inhibitory influences will be investigated with particular attention to the cholinergic, adrenergic and enkephalinergic systems.
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