Comparative effects of mu and kappa opiate agonists on the cecocolic motility in the pony.

The electrical and mechanical activity of the large intestine and its response to administration of opiate mu and kappa agonists were assessed from electrodes and inductograph coils chronically implanted on the cecocolic segment in six ponies given a diet of hay and concentrates. Before the drugs were given, migrating complexes propagating from the cecum into the colon occurred at the rate of 1.5 to 16/hour. During this propulsive activity, the cecocolic sphincter opened and closed allowing the outflow of cecal contents and preventing the backflow of colic contents. Each pony was used as its own control and was given fentanyl (0.01 and 0.05 mg/kg of body weight, IV) and U50488H (0.1 and 0.5 mg/kg, IV) at weekly intervals. The mu agonist fentanyl elicited a marked phase of inhibition of the propulsive activity and a closure of the cecocolic sphincter that lasted one to two hours depending on the dose. The kappa agonist U50488H induced an inhibition of the short spiking activity, i.e. of the resting muscle tone. It did not disturb the occurrence of migrating complexes nor that of the openings of the cecocolic sphincter. These kappa compounds may be drugs of choice to alleviate visceral pain in colic stases without inducing delay of transit unlike mu compounds.

Duodenal pH dips as an index of transpyloric flow in conscious dogs.

BACKGROUND: To determine if duodenal pH fluctuations might be used as a valuable index of the occurrence of gastric chyme ejection, the transpyloric flow and pH in the duodenal bulb were monitored simultaneously in six dogs. METHODS: Transpyloric flow, monitored by a chronically implanted electromagnetic flowmeter, was represented by individual pulses of flow. Relations between the volume of these flow pulses and changes in duodenal pH were assessed both postprandially and during the increased gastric outflow that followed gastric loading of buffered saline solutions at pH 2 and 4. RESULTS: During fasting and gastric loading with buffered saline at pH 2, no consistent relationship between flow pulses and duodenal pH fluctuations was evident. After instillation of buffer solution at pH 4 and postprandially, the magnitude of duodenal pH fluctuations became proportional to the stroke volume of the flow pulses. The removal of bile from the proximal duodenum decreased the relationship. CONCLUSIONS: It is concluded that duodenal pH measured at 2 cm from the pylorus might be used postprandially as an index of the transpyloric flow rate of chyme.

Central and peripheral motor effects of galanin on the duodenojejunum and colon in fed rats.

The effects of intraperitoneal, intrathecal and intracerebroventricular injections of the peptide galanin (GAL) on duodenojejunal and colonic motility were studied in conscious fed rats. At 0.3-3.0 nmol/rat, intraperitoneal GAL restored the 'fasted pattern' of duodenojejunal activity, i.e. the migrating myo-electric complex (MMC) was restored for a short period of time, and the MMC frequency was not significantly different from that observed before feeding. In addition, the activity of the proximal but not of the distal colon was significantly increased by GAL administration. The intracerebroventricular administration of GAL (0.03-0.3 nmol/rat) induced an MMC fasted pattern on the duodenojejunum after a latency period of about 1 h. In these experiments proximal colonic motor activity was significantly increased for 120-180 min. GAL given intrathecally (0.03-0.3 nmol/rat) induced a long-lasting fasted pattern of the intestinal activity within 10-20 min which was not dose dependent in duration, while the motility index of the proximal colon was significantly increased. Pretreatment with naloxone prevented the specific effects of GAL, given intracerebroventricularly or intrathecally, on the duodenojejunum and colon and the colonic response, but not the restoration of the MMC pattern on the duodenojejunum, induced by GAL given intraperitoneally. Ketoprofen pretreatment was completely ineffective. These observations indicate a plurality of sites of action of GAL on digestive tract motility including local duodenal receptors and suggest the importance of a spinal component in the control of motility by GAL when given intrathecally. Moreover the present results indicate the involvement of opioid receptors in the fasted pattern induced by GAL given intracerebroventricularly or intrathecally and in the colonic effects regardless of the route of administration.

Alterations of intestinal microflora by antibiotics. Effects on fecal excretion, transit time, and colonic motility in rats.

The effects of intragastric antibiotics in rats were examined on fecal microflora and excretion and through transit time and cecocolonic myoelectric activity. A solution of nonabsorbable antibiotics infused into the stomach for 20 days had a dramatic effect on the quantity, composition, and bacterial content of rat feces. Both the dry weight and the water content of feces were increased. The amount of short-chain fatty acids in the feces was dramatically lowered. However, neither total nor cecocolonic transit time of solids was affected. The cyclic organization of cecocolonic myoelectric activity was altered by antibiotic treatment, and the motility index, ie, the quantity of myoelectric activity recorded on the colon, progressively increased. An infusion of short-chain fatty acids modified this motor pattern but did not restore activity to a level comparable to that of control animals. In conclusion, intragastric antibiotics dramatically reduced intestinal microflora and increased fecal excretion of dry matter and water but did not affect the transit time of solid gut contents, although they did influence cecocolonic motility.

Relationships between pressure and flow across the gastroduodenal junction in dogs.

Antroduodenal pressure events were measured simultaneously with transpyloric flow, in conscious dogs, to evaluate the role of mechanical factors modulating this flow. The relationships between pressure and flow across the gastroduodenal junction were never linear. During the interdigestive state, terminal antral contraction occurred 0.9 +/- 0.29 s after the onset of the gush of gastric contents. Hence, the highest flow rate occurred during the period of lowest resistance. After a meal, terminal antral contraction began 3.3 +/- 0.87 s before the flow of chyme, and resistance rose simultaneously with flow rate. The antroduodenal resistance was 10 times higher than during the interdigestive state (8.33 +/- 1.56 vs. 0.73 +/- 0.34 mmHg.ml-1.s). The pyloroduodenal resistance was always lower than the antropyloric one. It is concluded that, because of the temporal relationship between motor events and flow, pure resistive behavior of the junction occurred only after a meal.

[Emptying of the abomasum in adult ruminants]. / Evacuation de la caillette chez les ruminants adultes.

In the adult ruminant, abomasal emptying is a permanent phenomenon depending upon meal volume. Intradian rhythm involving the motor pattern of the duodenum and circadian rhythm of unknown origin modulate the transpyloric flow rate. The fundic tone, antro-duodenal coordination and pyloric resistance regulate gastric outflow. The break-like function of the pyloric resistance involves chyme viscosity. Transpyloric flow rate is controlled by a hierarchy of extrinsic and intrinsic mechanisms triggered at the duodenal level. The vagus permanently inhibits the motility of the abomasum. A similar relationship is observed between the pyloric sphincter and duodenal motility. Removal of the pyloric ring leads to an increased food intake.

On the relevance of non-steroidal anti-inflammatory drugs in the prevention of paralytic ileus in rodents.

In the mouse, the gastrointestinal transit of a charcoal marker, halved following the intraperitoneal administration of acetic acid, was no longer inhibited after pretreatment with the non-steroidal anti-inflammatory drugs (NSAIDs), indomethacin, ketoprofen, piroxicam or ximoprofen (0.25-2.5 mg kg-1 orally). In the fasted rat, the migrating myoelectric complex pattern of the small intestine which was disrupted for about one hour by acetic acid was unaltered by pretreatment with indomethacin or ximoprofen (0.5 mg kg-1 i.p.). In the anaesthetized rat, the inhibition by about 50% of the gastrointestinal transit due to laparotomy, did not occur following treatment with NSAIDs. It is concluded that NSAIDs prevent the occurrence of chemically-induced and postoperative ileus in rodents, an effect probably related to the analgesic properties of NSAIDs.

Hyperphagia induced by pylorectomy in sheep.

In the hay-fed sheep, gastric (abomasal) contents are delivered continuously into the duodenal bulb at a mean flow rate of 210 ml per hour. The pylorus could behave as the site of origin of a feedback satiety signal by acting as a distal stomach sphincter limiting the abomasal emptying rate. This ability of the pyloric sphincter was confirmed by enhancement of abomasal outflow following either pylorectomy or pyloroplasty. In both cases, the subsequent reduction of the mean residence time of digesta in the abomasum was accompanied by an increase in the voluntary intake. The increase by 48% of food intake persisted several weeks after pylorectomy and was not only compensatory for the lower intake during recovery from surgery. Such an hyperphagia, obtained by removal of the ruminant herbivore pylorus, suggests the suppression at the antroduodenal junction level of a regulating factor affecting voluntary food intake by modulating the mean residence time of digesta in the abomasum.

Duodenal bulb control of the flow rate of digesta in the fasted and fed dog.

1. Continuous measurement of the flow of digesta near the pylorus, and 5 cm aborally, was assessed in the conscious dog using a chronically implanted flowmeter. The patterns of flow were related to motor activity of the gastroduodenal junction. 2. Electromagnetic measurement of the flow was calibrated in vitro by means of a pulsatile pump. Validation was obtained in vivo by direct evaluation of the amount of chyme collected from an open duodenal cannula and indirectly by a dye-dilution technique. 3. After a 12 h fast, only small amounts of gastric contents were delivered into the duodenum. This transfer occurred during periods of irregular motor activity recorded along the gastroduodenal junction, which occupied less than 25% of the recording time. The patterns of flow near the pylorus and beyond the duodenal bulb were correlated to antral and duodenal contractions respectively. 4. After a meal, gastric emptying occurred intermittently and was related to enhanced antral motor activity beyond the duodenal bulb; digesta flowed in clusters of gushes which were related to the duodenal contractions. 5. It is concluded that the mechanical role of the duodenal bulb is to change the intermittent juxtapyloric flow of digesta into a uniform flow at the duodenal level.

Involvement of serotonergic mechanisms in the disruption of ovine duodenal migrating myoelectric complex cycles by duodenal acidification.

Infusions of 1 and 4 mmol of HCl (pH 2.0) into the duodenal bulb of conscious sheep, within 30% of the period of the migrating myoelectric complex (MMC) cycle, induced aborally propagated premature phases of regular spiking activity (RSA) on the proximal duodenum. A transient inhibition of reticular contractions and a shortening of the period of subsequent duodenal MMC cycles were obtained with infusions of 4 mmol of HCl but not with infusions of 1 mmol. When the animals were pretreated with the 5-hydrotryptamine (5-HT) antagonists, ritanserin (0.2 mg/kg) and metergoline (0.5 mg/kg), 15 min before duodenal infusions of 4 mmol of HCl, premature RSAs and inhibition of reticular contractions were still elicited, but shortening of the subsequent duodenal MMC cycles did not occur. It is concluded that the shortening of duodenal MMC cycles induced by duodenal infusions of 4 mmol of HCl involved a serotonergic mechanism incorporating 5-HT2 receptors. The premature duodenal RSA and inhibition of reticular motility also elicited by these infusions appeared to be independent of this serotonergic system.

[Measurement of changes in parietal tonus of the abomasum in sheep]. / Mesure des variations du tonus pariétal de l'abomasum chez le mouton.

An inflatable bag of 250 ml at the pressure of 2 mm Hg inside the abomasal lumen was used to identify the abomasal smooth muscle tone. Reduced tone of the ovine abomasum was assessed, like for the fundic part of the canine stomach, in relation with the cyclic motor activity of the proximal duodenum. Opposite effects were obtained following parasympathomimetic drug injection versus peptides of the gastrin group, suggesting a high responsiveness of the abomasal smooth muscle tone to both neural and hormonal influences.

Flow and passage rate studies at the ileal level in the rabbit.

Six female rabbits fitted with a simple glass cannula in terminal ileum and a further 6 non-cannulated rabbits were used to perform digesta flow and transit measurements. The animals received ad libitum a diet based mainly on lucerne meal. Flow and transit measurements were carried out using two particulate markers: ytterbium (Yb) fixed on lucerne meal cell-walls by soaking, and chromium (Cr) fixed by mordancing. Both markers were incorporated in the same diet before pelleting. The digestibility coefficient or total mean retention time (MRTt) in the whole tract was not affected by cannulation. MRT values between cecum and rectum could be obtained in cannulated rabbits: 9.6 h. The MRTt values estimated with Yb were higher than those obtained with Cr because the size of particles labelled with Cr was probably greater and thus the particles were excreted more rapidly in hard feces. Flow measurements were not affected by the choice of marker, confirming indirectly the validity of ileal digesta samples. These first ileal flow measures obtained on cannulated rabbits indicate that about half (49%) of the digestible organic matter and two-thirds of the digestible crude protein apparently disappeared before the cecum. Cell-walls (CW), determined as NDF fraction, were totally recovered at the terminal ileum, although hemicellulose (NDF-ADF) digestion could occur in both the small intestine and the cecocolic parts. These results are discussed in relation to the specificity of the Van Soest method for digesta cell-wall analysis.

Prokinetic effects of cisapride, naloxone and parasympathetic stimulation at the equine ileo-caeco-colonic junction.

The electromyogram of the terminal ileum, the caecum and the proximal right ventral colon was recorded in fasted conscious ponies receiving intravenously equiactive doses of pilocarpine (0.05 mg/kg) and carbachol (0.01 mg/kg) as acetylcholine analogues; cisapride (0.1 mg/kg) and metoclopramide (2 mg/kg) facilitating acetylcholine release from myenteric neurones and naloxone (0.05 mg/kg) as an antagonist of the endogenous inhibitory opioid system. Both cisapride and naloxone induced typical migrating spike bursts in the colon associated with contractions of caecal body and caecal base. Both pilocarpine and carbachol stimulated the terminal ileum but had opposite effects on the activity of the caeco-colonic segment which was decreased by pilocarpine and increased by carbachol. High doses of metoclopramide had weak and unspecific stimulatory motor effects. It is concluded that a true prokinetic effect at the equine ileo-caeco-colonic junction requires a motor profile which includes coordination between contractions sequentially involving the body and the base of the caecum and migrating spike bursts on the proximal colon. Such changes in the motor profile were produced by cisapride and naloxone and to a lesser extent by carbachol.

Effects of intraluminal nutrients on intestinal myoelectric activity in rabbits.

In the unanesthetized rabbit, intraluminal infusions of D- and L-methionine, L-tryptophan, D-glucose, D-xylose, and lactulose had a biphasic effect on small intestinal myoelectric activity. A phase of enhanced activity was followed by a phase of inhibition. The excitatory phase was mimicked by saline solutions equiosmolar to the test solutions. The subsequent inhibition was does dependent and significantly (P less than 0.01) longer for the passively absorbed D-methionine than for the L-stereoisomer. The inhibitory action of 10 mM D-glucose, 10 mM L-methionine, and 5 mM L-tryptophan was blocked by propranolol on the jejunum and by phenoxybenzamine on the ileum. We conclude that the initial excitatory phase induced by luminal amino acids and sugars may be dependent on an action on osmoreceptors, whereas the subsequent inhibitory phase may involve the sympathetic noradrenergic system.

Gastroduodenal motor activity associated with gastric emptying rate in sheep.

1. Gastric emptying rate was calculated from dye dilution and was measured as the net flow over periods of 5 days through an electromagnetic probe inserted into a T-cannula, 5 cm beyond the pylorus in conscious hay-fed sheep. The net aboral flow was related to the motor activity of the antrum and duodenal bulb which was recorded via chronically fixed strain-gauge transducers. Nichrome wire electrodes were also implanted in order to quantify the electrical activity of the musculature associated with the abomasal outflow in sheep sustained on a liquid diet infused at fixed rates. 2. The abomasal outflow occurred as gushes of 2.1-9.2 ml associated with antroduodenal contractions during 90-95% of the recording time. In the sheep eating 0.7 kg/day hay, the daily outflow of chyme was 5.1 l which increased to 7.5 l of less viscous chyme when the sheep was fed 1 kg/day lucerne hay. During gastric infusion of 3.9 and 7.9 l of the liquid diet, the outflow was 5.7 and 8.3 l/day respectively of low-viscosity chyme propelled as gushes of 5.9-6.9 ml during 95% of the recording time. 3. Increasing the viscosity of the liquid diet with guar-gum caused a reduction in both antroduodenal motility and flow. Dilution of the liquid diet with saline doubled the flow as a result of an increase in the amplitude of the antral contractions. Circadian variations in outflow were also related to concomitant variations in antral motility. 4. It is concluded that the minute-to-minute flow rate of chyme through the pylorus could be satisfactorily measured at the duodenal bulb level and related to the motor activity of the antrum and duodenum. The rate of abomasal outflow depended primarily upon the strength of antral contractions, while the viscosity of the chyme also appeared capable of exerting a major influence on the outflow rate.

[Masticatory cycles of the rumination type in vagotomized lambs]. / Cycles masticatoires de type mérycique chez la brebis vagotomisée.

Contractions of the fluid-filled RR dependent upon the activity of the myenteric plexus were observed within 2 weeks after vagotomy in sheep maintained on a liquid diet. Spontaneous but not adrenergic evoked rumination was recorded beyond the 5th week after vagotomy. The observation of ruminating-like activity during 120 to 200 min per day in chronically-vagotomized sheep indicates that the onset of rumination does not require a gastric afferent pathway.