Phillips, Sidney F.

Scintigraphic techniques can measure sequentially gastric emptying, small bowel transit, and colonic transit in humans, and comparable methods for experimental studies in animals would be useful. We developed such a method in dogs and examined the effects of prokinetic drugs on regional transit. Two isotopes were given to fasting dogs. Polystyrene pellets labeled with99mTc were mixed in a can of dog food and111In- labeled pellets were given in a gelatin capsule coated with a pH-sensitive polymer, designed to dissolve in the distal bowel. Gamma camera images were obtained for up to 24 h. Prokinetic drugs were given by intravenous injection. Duplicate baseline studies showed good agreement in seven dogs. In a second group ( n = 4), intra- and interanimal variabilities were established. Two novel prokinetic drugs (AU-116 and AU-130) accelerated small bowel and colonic transit. A simple noninvasive method for measuring whole gut transit in dogs was developed and validated. Two new prokinetics accelerated small bowel and colonic transit.

The human colon can dilate, often to life-threatening proportions. Our aim was to explore nitrergic mechanisms underlying colonic dilation in conscious dogs with enterically isolated ileocolonic loops either extrinsically innervated ( n = 4) or extrinsically denervated ( n= 4). We recorded phasic pressures in ileum and ileocolonic sphincter (ICS), colonic tone, compliance, and relaxation during ileal distension. By NADPH-diaphorase histochemistry, we assessed effects of extrinsic denervation and enteric isolation on nitrergic fibers. Extrinsic denervation increased phasic pressures in ileum, ICS, and colon and abolished ICS and colonic relaxation in response to ileal distension. The nitric oxide synthase (NOS) inhibitor N ω-nitro-l-arginine (l-NNA) increased phasic pressures at all sites and ICS tone but did not abolish colonic relaxation during ileal distension in innervated loops. l-NNA reduced compliance and induced colonic high-amplitude propagated contractions in denervated loops. The NOS substrate donor l-arginine reversed effects ofl-NNA. The number of NADPH-diaphorase fibers increased in both enterically isolated preparations. Nonnitrergic extrinsic nerve pathways mediate reflex colonic relaxation during ileal distension. Enteric isolation augments the number of NOS fibers, an effect not modified by extrinsic denervation.

Summary In 4 dogs a 75-cm segment of jejunum was isolated from the intestinal stream. Stimulating electrodes were implanted at each end of the segment and recording electrodes at intervals between. The two ends of the segment were fashioned as stomas on the anterior abdominal wall. After recovery, the electrical activity of the segment was continuously recorded, whilst a solution of 100 mmol/l glucose and 90 mmol/l NaCl was infused into the proximal stoma at 2.9 ml/min. Effluent from the distal stoma was collected in 5-min aliquots for three consecutive 30-min periods. In the second period electrical stimuli were given via either the proximal or the distal bipolar electrodes to entrain pacesetter potentials. Both forward and backward electrical pacing decreased the output of water, glucose and sodium from the jejunal segment, but the decrease was significantly greater with backward pacing. We conclude that pacing a segment of jejunum backwards with electrical stimuli produces a greater increase in absorption from the segment than pacing it forwards, a finding which has therapeutic implications in patients with the short bowel syndrome.

AbstractSubstitution of the anorectum by a reservoir fashioned from the distal ileum can achieve the highly desirable goal of enteric continence after proctocolectomy and, not surprisingly, appears to enhance significantly the patient's quality of life. The potential price to be paid for this advance relates largely to uncertainties concerning the absence of the usual barriers to coloileal reflux and the presence of a stagnant, fecal pouch at the end of the small intestine. Moreover, positive experiences with conventional incontinent ileostomies over many years dictate that the Brooke ileostomy still remains the standard against which all other procedures must be judged. In the majority of patients, the presence of an ileal reservoir does not appear to have major adverse consequences; fecal volumes, fat excretion, overall gut function, and general health appear to be well maintained for the 10–15 years that patients with continent ileostomies have been followed. The follow‐up for ileo‐anal anastomoses is somewhat shorter. The pouches develop a fecal flora and mucosal histology is altered but, in most, no adverse sequelae have been noted. Nonspecific inflammation (“pouchitis”) occurs and is sometimes of major clinical significance, especially when also associated with systemic symptoms. The etiology of these conditions is unknown but bacterial overgrowth is suspected since antimicrobial therapy is often curative.