Verne E. Cowles

Differential Sensitivities of Morphine and Motilin to Initiate Migrating Motor Complex in Isolated Intestinal Segments Regeneration of Intrinsic Nerves

The effect of morphine and motilin on surgically isolated segments of small intestine was studied in 8 dogs. In 4 dogs, the small intestine was divided into four segments by simple transection and reanastomosis (group 1); in 4 others, a 2-4-cm colonic segment was interposed at each of the transection sites (group 2). The migrating motor complex initially cycled independently in each segment in group 1 dogs; after that the migration of the migrating motor complex across transection and reanastomosis began to recover and the recovery was complete 100 days after surgery. In contrast, in group 2 dogs the migration of the migrating motor complex from one segment to the next did not recover even 180 days after surgery. Morphine bolus or infusion initiated premature phase III activity in all segments but the sensitivity to morphine decreased distally. Motilin bolus or infusion initiated premature phase III activity only in the first three segments. The sensitivity to motilin also decreased distally. We concluded that (a) the interposition of a foreign segment severely impedes or prevents the regeneration of enteric nerves; (b) the sensitivity of morphine and motilin in initiating premature phase III activity decreases distally in small intestine; and (c) motilin does not initiate premature phase III activity in the ileum, but morphine may initiate premature phase III activity at all sites in the small intestine.

Opioid and nonopioid analgesic drug effects on colon contractions in monkeys

Opioid drugs administered postoperatively for pain relief cause increased frequency of nonpropulsive phasic contractions but decreased to absent propulsive migrating contractions in the colon, thus importantly influencing the duration of postoperative ileus. Ketorolac is thought to permit earlier return of bowel function postoperatively compared to morphine. Four monkeys had sets of three strain gauge force transducers implanted on the right and left colon at laparotomy. After recovery, animals were fasted overnight and had colon contractions recorded. After a 1-hr baseline period, 200 μg/kg morphine sulfate or 1 mg/kg ketorolac tromethamine was injected intramuscularly and recording continued. Each animal received four injections of each drug. Records were analyzed visually for frequency of phasic and migrating contractions. There was no difference in the frequency of phasic or migrating contractions after injection of ketorolac. Morphine, as expected, increased the frequency of phasic and decreased the frequency of migrating contractions in the colon. Ketorolac does not affect the frequency of colon contractions.

Motor activity and transit in the autonomically denervated jejunum

The role of extrinsic (autonomic) innervation in postprandial contractile activity of the small intestine is unknown. Using a canine model, we investigated the effects of complete extrinsic denervation on the parameters of fasting and postprandial jejunal contractions and their relationship to intestinal transit. Individual contractions were recorded using strain gauge transducers. Spatial and temporal parameters of contractions were analyzed by computer methods. Bolus injection of 14C-polyethylene glycol was used to calculate intestinal transit rates. Statistical comparisons of control and denervated animals were made by nonparametric tests. Extrinsic denervation did not abolish fasting or fed motor activity, but the following effects were observed: (1) the frequency of migrating motor complexes (MMCs) increased; (2) the onset of fed motor activity was delayed, and the duration of fed activity was shortened; (3) frequency, mean amplitude, and mean area of postprandial contractions were decreased; (4) fewer contractions propagated distally, and mean propagation distance was shortened; and (5) intestinal transit was slower for solids, but not for liquids. In the small intestine, extrinsic nerves modulate motor activity, which is under primary control of the intrinsic (enteric) nervous system.

Effects of transection and reanastomosis on postprandial jejunal transit and contractile activity

BACKGROUND The purpose of this study was to determine how transection and reanastomosis of the intestinal wall influences postprandial motor activity and transit in the small intestine. METHODS Six dogs were each instrumented with 12 strain gauge transducers, two collection cannulas, and an infusion catheter defining a 100 cm study segment in the midjejunum. The animals underwent baseline measurements of postprandial motor activity and transit rate after 650 kcal solid and liquid meals. Postprandial motor activity was analyzed by computer methods that identify frequency, duration, amplitude, and propagation behavior of smooth muscle contractions. After the baseline measurements were performed, each animal underwent transection and reanastomosis of the intestinal wall at sites marked during the initial laparotomy. Measurements of postprandial motor activity and transit were repeated and compared with control values. RESULTS Transection decreased frequency, amplitude, and percent propagation for postprandial contractions. Total propagating area per minute significantly decreased from 382 +/- 20 gram-seconds/minute to 190 +/- 66 gram-seconds/minute after transection (p < 0.05). Intestinal transit decreased from 13.5 +/- 1.5 cm/min to 8.5 +/- 2.4 cm/min (p < 0.05). The change in transit was related primarily to a change in frequency of propagating contractions (r = 0.767; p = 0.004). CONCLUSIONS Transection and reanastomosis of the intestinal wall changes the temporal and spatial organization of contractions distal to the transection site. The net result is fewer distally propagating contractions and slower intestinal transit.

Arginine vasopressin inhibits phasic contractions and stimulates giant contractions in monkey colon

Abdominal cramps and urgent defecation are common side effects of clinical doses of arginine vasopressin, indicating that the drug may have stimulating effects on colonic motor activity. Four strain-gauge transducers were implanted on the colon in six monkeys. A blood flow probe was fixed on the inferior mesenteric artery. After a 1-hour control recording, vasopressin, 0.13, 1.3, or 13.0 ng.kg-1.min-1, was infused intravenously for 90 minutes. The frequency of basal colonic contractions was reduced with increasing doses of vasopressin, but their mean amplitude and duration were not altered. Giant migrating contractions associated with defecation were initiated by the highest dose of vasopressin. Atropine had no effect on these giant migrating contractions but completely inhibited normal phasic contractions. Hexamethonium completely inhibited both giant migrating contractions and phasic contractions. Parasympathetic denervation of the colon did not inhibit giant migrating contractions initiated by vasopressin. Our findings suggest that the physiological concentrations of serum vasopressin present perioperatively may transiently inhibit spontaneous colon contractions but are unlikely to be the major cause of postoperative ileus. The giant migrating contractions initiated by vasopressin may account for the defecation associated with pharmacological doses of vasopressin. The initiation of giant migrating contractions by vasopressin may be mediated through a neural pathway.

Postprandial motor activity and its relationship to transit in the canine ileum

BACKGROUND The purpose of this study was to elucidate the mechanism of reduced intestinal transit rate in the ileum as compared with the jejunum. METHODS Twenty-one dogs were each instrumented with 12 strain gauge transducers, 2 collection cannulas, and an infusion catheter defining a 100 cm study in the midjejunum (n = 11) and midileum (n = 10). Postprandial motor activity and intestinal transit were measured 1 hour after ingestion of a 650 kcal solid meal. Contractile activity was analyzed by means of computer programs that determine frequency, amplitude, and propagation behavior of circular smooth muscle contractions. RESULTS Postprandial ileal contractions occurred with greater frequency (13.7 +/- 2.5 versus 11.5 +/- 0.4; p = 0.04) and displayed a higher incidence of propagation (61% +/- 2% versus 44% +/- 3%; p = 0.0001) than jejunal contractions, but traveled at significantly slower rates (1.0 +/- 0.7 cm/sec vs 3.7 +/- 0.9 cm/sec; p = 0.0001). The net result was significantly slower transit in the ileum compared with the jejunum (4.7 +/- 0.7 cm/min versus 13.1 +/- 1.5 cm/min; p = 0.0006). Within each region, transit correlated with parameters of propagating contractions. Stepwise regression of the combined data revealed that contraction velocity was the most important variable determining intestinal transit rate (r = 0.64; p < 0.001). CONCLUSIONS Contrary to previous thinking, postprandial ileal contractions display a high degree of temporal and spatial organization. Slow ileal transit is mainly due to reduced propagation velocity, which is intrinsic to the circular smooth muscle.

Effects of cholera toxin on small intestinal motor activity in the fasted state

We sought to determine the effect of cholera toxin on small intestinal motor activity in the fasted state and relate it to secretion in conscious dogs. Motor activity was recorded by strain gauge force transducers and secretion was measured by diverting it to the outside through a two‐way cannula. Inoculation of the study segment with cholera toxin resulted in a 10‐fold increase in fluid output by 120 minutes postinjection. At the same time that fluid output increased Significantly changes in fasting motor activity occurred. The cycle length of the migrating motor complex was significantly reduced, the percentage of phase II activity was significantly increased, and migrating clustered contractions were inhibited. Perfusion of the study segment by a nonabsorbable electrolyte solution at a rate similar to the rate of secretion induced by cholera toxin did not change the cycle length of migrating motor complexes, but the percentage of phase II activity was significantly increased as with cholera toxin, and migrating clustered contractions were inhibited. The reduction in the cycle length of migrating motor complexes seems to be a direct effect of cholera toxin on the gut wall while the increase in percentage of phase II activity and inhibition of migrating clustered contractions appear to be indirect effects due to fluid accumulation.