Actions of the novel gastrointestinal pro kinetic agent cisapride on equine bowel motility

The effect of cisapride was evaluated on the normal fasting bowel motility of four ponies with chronically implanted electromechanical transducers. Cisapride was infused over 60-min periods at 0.05 mg/kg (n = 4), 0.1 mg/kg (n = 5) and 0.25 mg/kg (n = 5). It produced marked and prolonged increases in electrical and mechanical activity at all sites examined. In the stomach there was increased total contraction activity with increased contraction amplitude and a slight reduction in rate. In the small intestine there was an increase in irregular (phase II) activity with an increase in number and amplitude of contractions and a decrease in the number of regular (phase III) activity fronts. There was a decrease in the number of phase III fronts that spread distally from the jejunum to the ileum. The phase II activity was coordinated temporally with prolonged activity in the stomach. Cisapride increased electrical and contractile activity in the left dorsal colon with increased contraction amplitude and an increase in electrical activity in the small colon. In the stomach and small intestine cisapride produced dose-dependent increases in activity but in the left dorsal and small colon the intermediate dose (0.1 mg/kg) produced the largest and most consistent responses. Side-effects observed were increased bowel sounds and frequency of defaecation, a slight increase in heart rate and transient signs of discomfort at the highest (0.25 mg/kg) dose rate.     

The action of low dose endotoxin on equine bowel motility

Post operative ileus (POI) is a common and serious complication of colic surgery in the horse. There is a high correlation between the incidence of POI and the presence of ischaemic bowel, suggesting a role for endotoxin. 0.1 micrograms/kg endotoxin was administered intravenously to six ponies with chronically implanted gastrointestinal electromechanical recording devices. It produced profound disruption of normal fasting bowel motility patterns, with an inhibition of gastric contraction amplitude and rate, left dorsal colon contraction product and small colon spike rate. In the small intestine an increase in abnormally arranged regular activity and a decrease in irregular activity was observed. There was no significant prolongation in stomach to anus transit time as assessed by the passage of plastic spheres. The bowel motility patterns induced by endotoxin could be mimicked by the intravenous infusion of PGE2 and less potently by PGI2 (prostacyclin), but not by PGF2 alpha. This study provides evidence that systematic endotoxin present in clinical cases of colic may play a role in the pathogenesis of equine ileus. The acute effects of endotoxin on bowel motility appear to be mediated indirectly by prostaglandins, and the inhibitory effects may be mediated mainly by PGE2.     

Gastrointestinal motility disorders and gastrointestinal prokinetic therapy.

Gastrointestinal motility disorders represent a diagnostic and therapeutic challenge. Disorders of gastrointestinal motility may result in accelerated transit, delayed transit, impaired relaxation, or inappropriate relaxation. The delayed transit disorders are the most important motility disorders of companion animals and may involve the esophagus (hypomotility and megaesophagus), stomach (delayed gastric emptying), small intestine (postoperative ileus and intestinal pseudo-obstruction), or colon (constipation and megacolon).     

Pathophysiology of equine postoperative ileus: effect of adrenergic blockade, parasympathetic stimulation and metoclopramide in an experimental model

An experimental model of postoperative ileus was developed in ponies using trauma to, and exposure of, a length of small intestine which gave rise to a reproducible and reversible set of changes in gut activity. This was assessed by recordings of electrical and mechanical activity and by propulsion of spheres from stomach to anus. Activity was depressed, especially in the stomach and colon, and transit was slowed. All drugs given increased electromechanical activity but propranolol was the least effective and did not alter the delayed transit of spheres. Yohimbine was more effective and the addition of bethanechol produced a little extra propulsive action. Metoclopramide had the best effect, virtually returning transit to normal and was the only drug fully restoring coordination of gastric and small intestinal activity which was disrupted by the ileus procedure. Loss of gastroduodenal coordination is probably the central lesion in equine ileus and may be mediated by dopamine.     

The effect of prostaglandin E1 on motility of the equine gut

Prostaglandin E1 was infused intravenously (25, 50 and 75 ng/kg/min) in three ponies. Changes in gastrointestinal mechanical and electrical activity were recorded from chronically implanted strain-gauge force transducers and electrodes. Dose-dependent responses were obtained: there were significant decreases in electrical spiking activity in the stomach, left large colon and small colon, with a corresponding decrease of activity in the left dorsal colon mechanogram. The small intestine was also affected, showing a decrease in both contraction rate and amplitude, which was more marked in the proximal jejunum than in the ileum. There was an association between these changes in gastrointestinal activity and the presence of discomfort and diminished gut sounds.     

Colonic α2-adrenoceptor-mediated responses in the pony

The motor responses of the caecum and colon to stimulation of alpha 2-adrenoceptors by xylazine and detomidine at the recommended dose levels of 0.6 and 0.1 mg/kg were investigated in three ponies. The motor changes of the left ventral colon induced by continuous intra-arterial infusion of a prostaglandin (PGF2 alpha) were used to assess the relative inhibitory effects of xylazine and detomidine in a colic model. The administration of alpha 2-agonists inhibited the spiking activity on the whole of the large intestine for 20-30 min (xylazine) or 2-3 h (detomidine). However, the detomidine-induced inhibition was preceded by a short period of increased smooth muscle basal tone as indicated by strain-gauge force transducer measurements. This pattern of activity was neither reversed nor prevented by the administration of tolazoline (10 micrograms/kg/min) intra-arterially. In contrast, inhibition of the colonic phasic and tonic motor activity by alpha 2-adrenoceptor stimulation was reversed competitively by tolazoline. The intra-arterial infusion of prostaglandin F2 alpha (10 micrograms/kg/min) induced prolonged and sustained spiking activity that might be related to signs of mild colic. Detomidine, and to a lesser extent xylazine, relaxed the whole of the large intestine and this was accompanied by alleviation of the signs of visceral pain.     

Myoelectric activity of the spiral colon in dairy cows

OBJECTIVE: To describe myoelectric activity of the spiral colon in healthy cows. ANIMALS: 7 lactating Simmental X Red-Holstein crossbred cows. PROCEDURE: Cows were implanted with 7 pairs of bipolar silver electrodes (4 in the spiral colon and 1 each in the cecum, distal part of the ileum, and proximal loop of the ascending colon [PLAC]). Myo-electric activity was recorded during 4 days for each cow. Patterns were analyzed, using computer-based methods. RESULTS: Myoelectric activity of the spiral colon was closely associated with motility of the ileum and PLAC and showed the typical organization of migrating myoelectric complexes (MMC). The MMC in the bovine spiral colon (bcMMC) had a mean +/- SD duration of 188.6 +/- 30.8 minutes and was divided into 4 phases. Phases I and II lasted 11.3 +/- 1.4 and 159.4 +/- 33.3 minutes, respectively. Phase III (duration, 5.4 +/- 1.2 minutes) was characterized by 5.2 +/- 0.9 regular spindles (35.4 +/- 5.4 seconds) and 1 final elongated spindle (137.2 +/- 56.4 seconds). Phase III most commonly (73.8 +/- 16.1%) was followed by phase IV (duration, 173 +/- 3.6 minutes). Propagation velocity of phase III was 4.4 +/- 0.5 cm/min, and 13.6% of bcMMC were incompletely propagated through the spiral colon. CONCLUSIONS: Myoelectric activity of the bovine spiral colon is composed of a recurring cyclic pattern similar to MMC of the small intestine. Data of colonic myoelectric activity in healthy cows will serve as a basis for studies on cecal dilatation and dislocation in cattle.     

Effect of romifidine on gastrointestinal motility, assessed by transrectal ultrasonography.

A technique of transrectal ultrasonography was developed to investigate the effects of romifidine 80 and 120 microg/kg bwt on intestinal motility in the horse. Motility of the small intestine, caecum and left ventral colon were assessed following injection of romifidine and a saline control, using a blinded, cross-over study design in 6 horses. Measurements were taken at 15, 30, 60, 120, 180 and 240 min after drug administration. There was a slight nonsignificant decrease in motility in the control group over the 4 h study period. Both doses of romifidine produced a marked decrease in gastrointestinal motility and were associated with the presence of reduced (nonpropulsive) contractions. Transrectal ultrasonography proved suitable for monitoring changes in the type and frequency of intestinal motility in the horse.     

Effects of medetomidine on intestinal and colonic motility in the dog

The motor responses of the jejunum and colon to stimulation of α₂-adrenoceptors by medetomidine and clonidine were investigated in four dogs. In fasting dogs, medetomidine, at a dose rate of 30 μg/kg i.v., disrupted the migrating myoelectric complex (MMC) pattern of the small intestine for about 2 h. Similar, but shorter-lasting effects were also induced by clonidine (30 μg/kg i.v.) on the jejunum. The administration of α₂-agonists inhibited colonic motility in fasting dogs, although medetomidine-induced inhibition was preceded by a short period of increased muscle tone. All these effects were reversed by the α₂-antagonists atipamezole (0.15 mg/kg i.v.) and yohimbine (0.20 mg/kg i.v.). In fed dogs, medetomidine (30 μg/kg i.v.) induced a strong increase of the tone on the proximal colon, while the activity of the medium and distal colon was completely suppressed. Yohimbine (0.50 mg/kg i.v.) immediately restored the activity of the colon and induced a propagated giant contraction and defaecation by the animal. These data confirm the importance of a₂-adrenergic receptors in the control of intestinal and colonic motility in the dog.     

Effect of exposure to dietary nivalenol on activity of enzymes involved in glutamine catabolism in the epithelium along the gastrointestinal tract of growing pigs.

Changes in the activity of enzymes involved in oxidative metabolism of glutamine, and in protein content, in the epithelial tissue along the gastrointestinal (GI) tract of growing pigs exposed to nivalenol (NIV) in the diet were investigated. The epithelial tissue was taken from the stomach, small intestine and colon of three groups of animals fed diets without NIV (control), with inclusion of 2.5 mg NIV/kg diet (low dose) and with inclusion of 5.0 mg NIV/kg diet (high dose). The activities of glutaminase, glutamate dehydrogenase, oxoglutarate dehydrogenase, isocitrate dehydrogenase and alanine aminotransferase were determined. In the control pigs the activities of oxoglutarate dehydrogenase and alanine aminotransferase were higher (P < 0.05) in the epithelium of the small intestine as compared with the stomach and colon, while there were no differences in the activities of glutaminase, glutamate dehydrogenase and isocitrate dehydrogenase. With increasing inclusion of NIV in the diet the activity of oxoglutarate dehydrogenase decreased (P < 0.05) in the epithelium of the small intestine and colon, and the activity of alanine aminotransferase tended (P = 0.07) to increase in the epithelium of the small intestine. The activities of glutaminase, glutamate dehydrogenase and isocitrate dehydrogenase remained unaffected by the inclusion of NIV in the diet. In the control pigs the protein content in the epithelium of the small intestine was higher (P < 0.05) than in the stomach and colon, while there were no effects of NIV inclusion in the diet on the protein content. It can be concluded from the present study that the epithelial tissue of the small intestine and colon of pigs exposed to a diet containing NIV will have a reduced enzymatic capacity to utilise alpha-ketoglutarate in the tricarboxylic acid cycle (TCA-cycle), suggesting an impaired energy supply to these organs.     

Pharmacological modulation of postprandial colonic motor activity in the pony

The contractile activity of the equine large intestine exhibited a biphasic response to feeding: enhancement of migrating complexes passing along the colon and an increase of 50% in cyclic variations in smooth muscle at intervals of 20 min on the left ventral colon for a period of 5 to 7 h postfeeding. The cholinergic agonist, bethanechol (50 micrograms/kg subcutaneously), induced both the migrating complexes and the cyclic variations at intervals of 10-15 min. In contrast, the intra-arterial infusion of PGF2 alpha (3 micrograms/kg/min) increased the contractile activity during infusion, but without inducing distinct patterns of activity. Atropine but not indomethacin or flunixin pre-treatment prevented the effects of postprandial, cholinergic and PGF2 alpha stimulation of colonic motility, suggesting that the gastrocolonic reflex involved mainly cholinergic stimulation of the caecum and replicated colon, including the prostaglandin F2 alpha excitatory effects.     

Effects of erythromycin on myoelectric activity of the spiral colon of dairy cows

The effects of erythromycin on myoelectric activity of the spiral colon of dairy cows were investigated in a prospective study. Four Simmental x Red-Holstein crossbred cows of similar body weight and condition with seven pairs of bipolar electrodes implanted in the intestine (one each in the distal ileum, caecum and proximal colon, and four in the spiral colon) were included. Erythromycin lactobionate (1 mg kg(-1)) and 0.9% sodium chloride solution (NaCl) were administered to each cow in a random order. Erythromycin was diluted with NaCl and both treatments were administered slowly intravenously over a period of 5 min 1 h after onset of a phase III of the bovine colonic migrating myoelectric complex (bcMMC). A 3-6-day washout period was scheduled between trials. Significant differences between the results of the treatments were observed for spike duration in phase I as well as for spike duration and duration of spiking activity during phase II of the second bcMMC, which were significantly higher after erythromycin treatment than after NaCl. These findings suggest an indirect effect of erythromycin on colonic motility in cattle.     

Myoelectric activity in the intestine of cows with strangulating obstruction of the distal small intestine

Myoelectric activity in 2 cows instrumented with permanent electrodes in the ileum, cecum, proximal loop of the ascending colon (PLAC), and spiral colon was analyzed after an obstruction developed in the distal small intestine. Results were compared with patterns from a group of 7 normal cows. Myoelectric activity in the ileum immediately orad to the occlusion was characterized by abolition of the migrating myoelectric complex (MMC) and a constant pattern of strong spike bursts of long duration. Cyclic activity was present in all parts of the large intestine, and propagation of phase III activity was evident from proximal to distal. A slight degree of disorganization in phase III propagation was restricted to the spiral colon. Activity cycles tended to be shorter in the cecum and PLAC of both cows with colic than in normal cows, and the intensity of spiking activity was generally lower. Changes in duration of the MMC in the spiral colon (bovine colonic MMC, bcMMC) were inconsistent, but the intensity of spiking activity tended to be lower in phases I and II of both cows compared to controls. The organization of phase III in several spindles typical of the bovine spiral colon was not disrupted, but phase IV of the bcMMC occurred only infrequently. Organized cyclic activity occurred in the large intestine of both cows despite complete disruption of the small intestinal MMC, indicating the presence of mechanisms able to initiate and regulate coordinated myoelectric patterns in the large intestine independent of the small intestine.     

Electromyoenterography During Normal Gastro-Intestinal Activity, Painful or Non-painful Colic and Morphine Analgesia, in the Horse

The electrical potentials were recorded from the antrum, the duodenum, the ileum and the first part of the colon of ponies under (a) normal resting conditions, (b) during nonpainful colic and (c) after intravenous morphine administration.

The normal pony, at rest, had five contractions of the antrum per minute. On the small intestine, the basal electrical activity decreased from the duodenum (14-15/min) to the ileum (10-11/min). The small bowel also had three types of motility: peristaltic waves, rhythmic segmentations and random contractions. On the colon, bursts of potentials indicating intense motor activity occurred at the rate of 20 to 30 per hour. Morphine given intravenously (IV) greatly increased the frequency of the electrical potentials of the antrum and the longitudinal bands of the colon.

During non-painful colic, hyperactivity of the cranial small intestine was continuous. Spasms of the jejunum occurred every minute and could not be relieved by morphine (IV).

When colic was painful, jejunal spasms announced the crisis of intense abdominal pain. After morphine (IV) the spasms and pain disappeared; the jejunum remained hyperactive, the motility of the colon was increased while the antrum became quiet.

     

RADIOGRAPHY AND IMAGE-INTENSIFIED FLUOROSCOPY OF BARIUM PASSAGE THROUGH THE GASTROINTESTINAL TRACT IN SIX HEALTHY AMAZON PARROTS (AMAZONA AESTIVA)

Gastrointestinal contrast studies were performed in six clinically healthy blue-fronted Amazon parrots (Amazona aestiva) using radiography and image-intensified fluoroscopy. During examination, the birds were confined in a perspex cage. The quality of the lateral radiographs was adequate for assessment of the contrast medium-filled gastrointestinal tract. Thirty minutes after administration of 20 mL/kg of a 25% barium sulphate suspension directly in the crop, in all birds the ventriculus was totally outlined by barium. After 60 min, the small intestine was filled in five of six birds. After 180 min, the crop was empty in all birds. The barium-outlined ventriculus had differences in shape on radiographs of individual birds and also between birds. The colon and cloaca had further filling after 120 to 300 min. With image-intensified fluoroscopy, gastrointestinal motility was evaluated. Contractions of the crop were seen, and boluses of contrast medium passing through the esophagus toward the proventriculus were easily identified. Proventricular contractions were rarely noted, but ventriculus motility was present and clearly defined. The ventriculus had a mean of 3.7 contraction cycles/min. In the duodenum and small intestine, rapid antegrade and retrograde peristaltic movements in combination with segmental contractions were seen. In the colon, occasionally very slow peristaltic activity, mainly of segmental nature, was present. During the examinations, no defeacation was recorded. Confinement in a small perspex cage provides an adequate and handy radiological set-up for evaluation of gastrointestinal passage and motility in birds, minimizing the influences of stress and anesthesia.     

THE NORMAL UPPER GASTROINTESTINAL EXAMINATION IN THE FERRET

Upper gastrointestinal examinations were performed in 11 unsedated ferrets and 4 ferrets sedated with ketamine and diazepam. Each animal received a 8-13 mL/kg body weight dosage of barium liquid (30% weight:volume). Radiographs were made immediately and at 5, 10, 20, 40, 60, 90, 120 and 150 min (mins) after the barium was administered. Gastric emptying began immediately. Mean total gastric emptying was longer in sedated ferrets (130 +/- 40 min versus 75 +/- 54 min); however, this difference was not statistically significant (p = 0.18). Small intestinal transit time was less than 2 h in all ferrets. The barium-filled small bowel was best visualized on the 20- and 40-min radiographs and did not exceed 5-7 mm in width. Flocculation of barium in the small intestine and adherence of barium to the stomach mucosa was seen in almost all animals. The longitudinal colonic mucosal folds in the colon were well visualized in the normal upper gastrointestinal study and aided in distinguishing small intestine from large intestine. The use of ketamine and diazepam sedation did not significantly affect the parameters evaluated in the upper gastrointestinal study series.     

Reference Values and Repeatability of Transabdominal Ultrasonographic Gastrointestinal Tract Thickness and Motility in Healthy Donkeys (Equus asinus)

The present study aimed to provide reference ranges for the wall thickness and motility pattern of the gastrointestinal tract from a sample of donkeys (Equus asinus) population using B-mode ultrasonography. In the present study, 30 clinically healthy donkeys (Equus asinus) (15 males and 15 females), aged 2–20 year old and weighed 100–280 kg were randomly selected for B-mode ultrasonographic scanning of the abdomen. The wall thickness of the stomach, duodenum, jejunum, left colon, right colon, and cecum was assessed. Moreover, the motility pattern of the duodenum, jejunum, left colon, right colon, and cecum was evaluated over a period of 3 minutes. Abdominal ultrasonographic scanning of the gastrointestinal tract of healthy donkeys explored that the stomach, duodenum, jejunum, left colon, right colon, and cecum could be visualized easily. The wall thickness of the stomach, duodenum, jejunum, left colon, right colon, and cecum was 7.0 ± 0.9 mm, 3.3 ± 1.0 mm, 5.4 ± 0.6 mm, 5.1 ± 0.5 mm, 5.4 ± 0.5 mm, and 5.4 ± 0.6 mm, respectively. The thickest part of the gastrointestinal tract is the stomach, whereas the thinnest part is the duodenum. The motility pattern of the duodenum, jejunum, left colon, right colon, and cecum was 7.7 ± 1.3 contractions/3 minutes, 6.9 ± 1.1 contractions/3 minutes, 4.1 ± 1.2 contractions/3 minutes, 5.5 ± 1.3 contractions/3 minutes, and 4.0 ± 0.8 contractions/3 minutes, respectively. Both the duodenum and jejunum contractions were significantly higher than that of the left colon, right colon, and cecum. This is the first study reporting the reference values for both the wall thickness and motility pattern of the gastrointestinal tract in healthy donkeys (Equus asinus) in Egypt. Good knowledge of these standard and reference values of the wall thickness and motility pattern of gastrointestinal tract structures represents a step in the early diagnosis of the gastrointestinal disorders, including colic in such animal species.     

New approach to the fed pattern: feeding evokes the specific spike burst setting in the small bowel of non-fasted sheep

As feeding is not a factor disrupting the migrating motor (myoelectric) complex (MMC) in sheep, it is presumed that the fed pattern is absent in this animal species. In turn, feeding may stimulate ovine gastrointestinal motility. To verify this discrepancy the myoelectric activities of the antrum and duodeno-jejunum were recorded in seven adult sheep. Additionally, the relationship between electrical and mechanical activity was tested in four of these animals by means of strain gauge force transducers mounted near the duodenal electrodes. Chronic experiments were conducted in fasted and non-fasted sheep before, during, and after standard feeding. Fodder was offered during the duodenal phases 1, 2a, or 2b of the MMC. Two types of responses to feeding (an unspecific and a specific fed pattern) were denoted. A simple increase in spike burst intensity, i.e. without their special deployment and assessed as the myoelectric activity index (unspecific fed pattern), was observed in the abomasal antrum and small bowel during and after feeding in the course of phase 2b of the MMC in non-fasted and fasted sheep. In the abomasal antrum its duration was longer than in the small intestine. In non-fasted animals the unspecific fed pattern was more pronounced in the abomasal antrum than in the small bowel, while its duration was longer in fasted animals. The specific fed pattern was evoked in the duodeno-jejunum during feeding initiated in the course of phase 2b of the MMC exclusively in non-fasted animals. During this pattern, the spike burst series were significantly reduced compared with those which appeared during phase 2b of the MMC and dispersed single spike bursts predominated. The average duration of the specific fed pattern was 3-4 min and it arrived 2-7 min after feeding onset. In the remaining periods during feeding, the spike burst pattern resembled that often observed during phase 2b of the MMC. Thus the confined fed pattern is present in sheep and its character depends upon the gastrointestinal region and feeding habits.     

Colonic motor responses in the pony: relevance of colonic stimulation by opiate antagonists

The electrical and mechanical activity of the digestive tract and its response to the administration of opiate agonists and antagonists was assessed from electrodes and strain gauges chronically implanted on the jejunum and the cecocolonic segments in 3 ponies given a diet of hay and concentrates. Before the drugs were given, 10 to 17 migrating myoelectric complexes/day were recorded on the small intestine, and a rhythmic motor activity (base line) was observed on the proximal portion of the colon at the rate of 3.5 to 6.6/hour. Propagated contractions from the proximal to the distal portion of the colon occurred at the rate of 1.5 to 2.3/hour. Each pony was used as its own control and was given morphine (0.5 or 1 mg/kg of body weight, IV) or fentanyl (0.01 or 0.05 mg, IV) at weekly intervals. After an early phase of inhibition of the overall activity that lasted from 0.5 to 3 hours, depending on the dose, the resting muscle tone of the colonic activity was increased for a dose-dependent period. Propagated contractions only reappeared at the end of this 2nd phase. The opiate antagonist naloxone (0.5 mg/kg, IV) elicited a marked propulsive activity on the left replicated colonic segment, characterized by an increase in the number of propagated contractions. The N-methyl-quaternary analog of naloxone (methylnaloxone, which presumably entails selective action at opiate receptors outside the CNS) was also effective, indicating peripheral effects at the dosage level used (0.5 mg/kg, IV). Seemingly, an inhibitory opioid system exists in the control of colonic motor function in ponies and the possible usefulness of opiate antagonists to relieve hypomotility resulting in colonic impaction and constipation.     

COMPARATIVE ORGAN IMAGING: THE GASTROINTESTINAL TRACT

Diagnostic radiology of the esophagus, stomach, small and large intestine, mesentery, and pancreas is reviewed. Survey and contrast radiography remain the principal imaging methods used to evaluate gastrointestinal diseases in animals. Of the other imaging techniques, scintigraphy has potential in assessment of esophageal and gastric motility disorders, and detection of intestinal hemorrhage. Ultrasonography is useful for imaging the pancreas and gastrointestinal mass lesions.