Prokinetic effect of the 5-HT4R agonist mosapride on canine gastric motility

We assessed prokinetic action of gastroprokinetic agent, mosapride in dogs. Open-label cross-over study. Six healthy beagles were administered single oral mosapride at doses of 0.5, 0.75, 1, and 2 mg/kg 30 min prior to feeding, followed by 1-week interval. The motility index (MI) of gastric contraction was ultrasonographically evaluated by change rate of antral area and contraction number. Significant increases in MI were observed at doses of 0.75 mg/kg (mean ± SEM, 11.11 ± 0.19), 1 mg/kg (11.65 ± 0.34), and 2 mg/kg (12.04 ± 0.34), compared with that of the control (9.37 ± 0.51). Mosapride administration (2.0 mg/kg, BID) for 1 week had no adverse effects on blood tests or health of the animals. In conclusion, 0.75 to 2 mg/kg of mosapride produces gastric prokinetic actions without adverse effects.     

The prokinetic effect of mosapride citrate on horse gastric emptying rates

The prokinetic effect of the 5-HT4 receptor agonist mosapride was evaluated in seven healthy thoroughbreds. Mosapride was orally administered at doses of 0.5, 1.0 or 1.5 mg/kg. The breath 13CO2/12CO2 rate (Delta13CO2), an indirect indicator for the rate of gastric emptying, was measured at appropriate points for 4 hr after drug administration. There was a significant increase compared with the control value at 15, 20 and 165 min for 0.5 mg/kg, 30 min at 1.0 mg/kg and 165 min for 1.5 mg/kg. The results suggest that mosapride may facilitate the gastric emptying in horses.     

Effects of mosapride citrate, metoclopramide hydrochloride, lidocaine hydrochloride, and cisapride citrate on equine gastric emptying, small intestinal and caecal motility

Objective

Although extensive work has been done to elucidate the beneficial and unfavorable effects of gastrointestinal prokinetic agents in humans, little is known on the effects of these agents in horses. In this study, we compared the effects of mosapride, metoclopramide, cisapride, and lidocaine on equine gastric emptying, jejunal and caecal motility and evaluated these agents’ adverse drug reactions (ADRs).

Animals

Seven healthy adult Thoroughbreds.

Procedure

Mosapride 1.0 mg/kg and 2.0 mg/kg, metoclopramide 0.2 mg/kg, and cisapride 1.0 mg/kg were dissolved in 100 mL distilled water for oral administration. Lidocaine 1.3 mg/kg was mixed with 500 mL saline for a 30-min intravenous infusion. Oral administration of 100 mL distilled water was used as control. Gastric emptying was evaluated using ¹³CO₂ breath test, and jejunal and caecal motility was assessed by electrointestinography.

Results

The present study demonstrates that mosapride at doses of 1.0 mg/kg and 2.0 mg/kg facilitates gastric emptying in horses. Improved jejunal motility was observed following administration of mosapride (1.0 mg/kg and 2.0 mg/kg), metoclopramide (0.2 mg/kg), and cisapride (1.0 mg/kg). Similarly, improved caecal motility was observed following administration of mosapride (2.0 mg/kg).

Conclusions and clinical relevance

This study shows that among the prokinetic agents studied here, only mosapride (2.0 mg/kg) promotes jejunal and caecal motility in horses. Considering mosapride ADRs profile, it is believed that this compound is useful in the treatment of diseases associated with decreased GI motility, including postoperative ileus.     

USE OF IOHEXOL AS A GASTROINTESTINAL CONTRAST MEDIUM IN THE DOG

Iohexol was administered orally in five dogs. The dose, gastrointestinal (GI) transit time, appearance of mucosal patterns and side effects were studied. Three different doses (525, 700, 875 mgI/kg) were used in each dog at 1-week intervals. GI transit time was rapid. In each dose, gastric emptying commenced immediately after administration of the contrast medium, and was completed within 30–60 min with doses of 525–700 mgI/kg and 90–120 min with 875 mgI/kg. Large intestinal filling was observed within 60-90 min. In the majority of studies, the mucosal border appeared as a thin homogeneous halo of lucency surrounding the more opaque bowel lumen contents. The contrast intensity was not adequate with the lowest dose. The image quality did not deteriorate along the GI tract. No adverse reactions were found. Iohexol is an alternative GI contrast medium in the dog when contrast media are contraindicated.     

Real-time ultrasonographic evaluation of canine gastric motility in the postprandial state

Gastric motility is affected by several pathological conditions which may induce upper gastrointestinal clinical symptoms. The pathogenesis of canine gastric motility disorders is poorly understood because of methodological limitations. This study aimed at establishing a simple method for evaluating postprandial gastric motility in dogs. Gastric motility was ultrasonographically assessed in 7 healthy beagles using a technique previously described in humans. The motility index (MI), an indicator of gastric antral motility, was calculated by measuring the area of the gastric antrum in both a contracted and relaxed phase and by counting the number of contractions. The MI was measured every 30 min for 3 hr after feeding and compared with gastric emptying as assessed by a (13)C-octanoic acid breath test. The MI at 30 min had the lowest variability in the 7 dogs (mean SD, 9.77 ± 0.42; coefficient of variance, 4.25%), and a significant correlation was observed with gastric emptying coefficient (R(2)=0.8126, P=0.005) and half-emptying time (R(2)=0.654, P=0.027). When atropine was administered, a significant decrease in the MI at 30 min was observed compared with the control (9.77 ± 0.42 vs. 5.19 ± 0.22, P=0.0003). In conclusion, evaluation of the MI at 30 min is suitable for assessing gastric motility and enables us to assess gastric motility simply in a short time. By using this method, further studies for the pathogenesis of canine gastric motility disorders are warranted.     

Botulinum toxin A as a treatment for delayed gastric emptying in a dog

A toy Australian shepherd dog was referred for bile peritonitis following excision of a biliary mucocele. Subsequent delayed gastric emptying was refractory to prokinetic therapy but responded to injection of botulinum toxin A into the muscularis layer of the pylorus; a novel therapy for delayed gastric emptying in dogs.     

Gastric Drainage Procedures: Effects in Normal Dogs II. Clinical Observations and Gastric Emptying

Complete gastric emptying time using barium sulfate mixed with commercial canned dog food was measured radiographically in 29 mature mixed breed dogs before and 3 to 4 weeks after Fredet-Ramstedt pyloromyotomy (FRP) (6 dogs), Heineke-Mikulicz pyloroplasty (HMP) (6 dogs), Finney pyloroplasty (FP) (6 dogs), Jaboulay's gastroduodenostomy (JG) (6 dogs), and antral gastrojejunostomy (AG) (5 dogs). The dogs were observed for clinical evidence of side effects. Postoperative endoscopic examination and double contrast gastrography were performed to subjectively evaluate the diameter of the gastrointestinal communication and the amount of enterogastric reflux. Although none of the procedures significantly (p < 0.05) altered gastric emptying time, the overall tendency was toward slowing down gastric emptying time. The severity of gastrointestinal side effects and enterogastric reflux appeared to be related to the size and/or location of the gastrointestinal opening.     

Diagnosis and treatment of gastric motility disorders.

A disorder of gastric motility should be suspected in patients with chronic vomiting. Imaging studies are used to confirm delayed gastric emptying, the most common form of a gastric motility disorder. Other causes of chronic vomiting, for example, metabolic or endocrine disorders, other abdominal disorders, mechanical causes of gastric obstruction, and lower gastrointestinal tract disease, are then ruled out. If no underlying cause is determined, a functional disorder of gastric emptying is presumptively diagnosed. Treatment consists of dietary management and gastric prokinetic agents. Cisapride is the drug of choice for treating delayed gastric emptying followed by erythromycin and ranitidine or nizatidine.     

Gastric mucosal lesions in dogs with acute intervertebral disc disease: characterization and effects of omeprazole or misoprostol

We characterized gastric mucosal lesions in dogs with acute degenerative disc disease treated by surgery and corticosteroid administration. The effect of omeprazole and misoprostol on gastric lesions in these dogs was also evaluated. Dogs were randomly assigned to 1 of 2 treatment groups or to the control group. Treatment consisted of omeprazole at 0.7 mg/kg orally once daily, or misoprostol at 2 microg/kg orally 3 times daily. All 3 groups received dexamethasone at 2 mg/kg on day 0, prednisolone at 2 mg/kg on day 1. prednisolone at 1 mg/kg on day 2, and prednisolone at 0.5 mg/kg on all further days (range, 5-6 days). Endoscopic examination was performed on day 0 and 5-6 days later. Four regions of the stomach were qualitatively scored from 1 to 12 based on the presence of submucosal hemorrhage, erosion, or ulceration, with ulceration receiving the highest numerical score. Nineteen of 25 dogs had gastric mucosal lesions at the beginning of the study. No significant difference was found in the gastric lesion score among the 3 groups at the end of the study. Gastric mucosal lesions were concluded to be common in dogs with acute degenerative disc disease treated with corticosteroids. Neither omeprazole nor misoprostol at the doses used was effective in healing or preventing the further development of gastric mucosal lesions.     

Gastric emptying of nondigestible radiopaque markers after circumcostal gastropexy in clinically normal dogs and dogs with gastric dilatation-volvulus.

Using radiopaque particles mixed with food, gastric emptying was assessed in healthy dogs not subjected to surgery, in healthy dogs 9 to 35 days after circumcostal gastropexy, and, in dogs 1 to 54 months after surgical treatment and recovery from gastric dilatation-volvulus (GDV). Circumcostal gastropexy surgery did not alter the 90% gastric emptying time for radiopaque particles in healthy dogs. However, 90% gastric emptying time was significantly (P less than 0.05) increased after circumcostal gastropexy in dogs with GDV, compared with healthy dogs after the same surgical procedure and recovery period. These results imply that dogs with GDV have delayed gastric emptying of solid particles. Whether delayed gastric emptying of markers detected in affected dogs after surgical treatment and recovery was the result or the cause of GDV was not determined. Results indicate that circumcostal gastropexy could be recommended as a prophylactic procedure for GDV in large breeds with deep thorax, because delayed gastric emptying of markers secondary to the surgical procedure is unlikely.     

COMPARISON OF THE EFFECT OF LAPAROSCOPIC AND CONVENTIONAL PYLORIC SURGERY ON GASTRIC EMPTYING IN DOGS

The effect of a laparoscopic approach and pyloric surgery on canine gastrointestinal activity, particularly gastric emptying time, is not well understood. The purpose of this study was to compare the effect of laparoscopic and conventional pyloric surgery, in Ramstedt pyloromyotomy and Heineke-Mikulicz pyloroplasty, on complete gastric emptying time in 20 clinically normal dogs. Dogs were divided into four groups of five animals: dogs with laparoscopic Ramstedt pyloromyotomy, conventional Ramstedt pyloromyotomy, or laparoscopic Heineke-Mikulicz pyloroplasty, and the conventional Heineke-Mikulicz pyloroplasty group. Gastric emptying time using barium sulfate mixed with dry kibble dog food was measured fluoroscopically before and 1 month after surgery. Gastric emptying of solids was significantly enhanced in the pyloroplasty groups in the postoperative period compared with preoperative emptying. Just as after conventional pyloromyotomy, gastric emptying time after laparoscopic pyloromyotomy was not statistically different as compared with preoperative values. This study indicates that the fluoroscopic test meal is a valuable tool for defining complete gastric emptying time in normal dogs. We conclude that pyloromyotomy was less effective in decreasing complete gastric emptying time than Heineke-Mikulicz pyloroplasty in normal dogs. The possibility of decreasing complete gastric emptying time by laparoscopic surgery suggests a potential clinical application for this technique in small animals.     

Prevention of adverse reactions following milbemycin D administration to microfilaremic dogs infected with Dirofilaria immitis

Some adverse reactions such as shock-like reaction and dirofilarial hemoglobinuria (caval syndrome) occasionally occurred in microfilaremic dogs following milbemycin D (Milbe) administration. This study was carried out to seek the prevention of these adverse reactions. In two groups containing 16 and 9 dogs respectively which were administered either chlorpheniramine maleate (1 mg/kg) or indomethacin (2.5 mg/kg) simultaneously with Milbe (1 mg/kg), the incidence of clinical signs such as the pale color of the visible mucous membranes, respiratory disorders, caval syndrome and shock-like reaction as well as changes in clinical parameters such as RBC and WBC counts, WBC profile and serum total protein, were almost equal to that observed in the group administered Milbe alone. In 41 dogs administered prednisolone (1 mg/kg) simultaneously with Milbe (1 mg/kg), no shock-like reaction was observed. Changes in clinical parameters were different from those in the group administered Milbe alone, whereas some clinical signs of adverse reactions, including caval syndrome, were observed. These results indicated that prednisolone was effective for prevention of the shock-like reaction in microfilaremic dogs induced by Milbe.     

Gastroscopic food sensitivity testing in 17 dogs

Seven of 17 dogs with gastrointestinal signs and suspected dietary intolerance had positive responses to gastroscopic food sensitivity testing (GFST). Five of the non-responders and six of the dogs that responded to GFST were successfully treated with dietary control alone. The seventh dog that responded to GFST had an ileal adenocarcinoma and did not survive to follow-up. Local reactions to GFST included mucosal oedema, mucosal hyperaemia and gastric hyperperistalsis and systemic reactions consisted of hyperventilation and retching. The character of the responses to GFST is consistent with a type 1 hypersensitivity reaction to the food antigen, suggesting that IgE may mediate dietary sensitivity in some dogs. Positive responses to GFST may, therefore, demonstrate gastric mucosal hypersensitivity to food antigens and be useful in formulating therapeutic diets; negative responses need to be interpreted with caution. The limitations of the procedure are that it requires a videoendoscopy system, may significantly add to general anaesthetic time and will only detect immediate reactions.     

ASSESSMENT OF BARIUM IMPREGNATED POLYETHYLENE SPHERES (BIPS®) AS A MEASURE OF SOLID-PHASE GASTRIC EMPTYING IN NORMAL DOGS-COMPARISON TO SCINTIGRAPHY

Barium impregnated polyethylene spheres (BIPS) are radiopaque markers used for investigation of a variety of gastrointestinal disorders. One proposed use of the small (1.5 mm) marker is quantitative assessment of solid-phase gastric emptying, which may offer a simple, inexpensive alternative to nuclear medicine studies. In this study the rate and pattern of gastric emptying of a radiolabeled meal containing 30 small BIPS was evaluated in normal dogs by simultaneous comparison of the radiopaque marker method and a scintigraphic method. Serial scintigraphic images and radiographs were obtained for 8 hours or until 95% of the markers had left the stomach. Emptying curves were constructed and statistical analyses performed. There were significant differences in gastric emptying times and lag phase characteristics between the BIPS and scintigraphic studies. These results indicate that in normal dogs there are differences in both the rate and the pattern of solid-phase gastric emptying of a radiolabeled meal as assessed by scintigraphy and the gastric emptying of small BIPS.     

Comparison of Two Regimens for the Treatment of Meningoencephalomyelitis of Unknown Etiology

Background: The optimal treatment for meningoencephalomyelitis of unknown etiology (MUE) remains unknown, despite the widespread use of a variety of immunosuppressive drugs.
Objective/Hypothesis: To compare the efficacy of prednisolone combined with either vincristine and cyclophosphamide (COP group; n = 10) or with cytosine arabinoside (AraC group; n = 9).
Animals: Nineteen dogs with neurological deficits, neuroimaging, and cerebrospinal fluid abnormalities consistent with a diagnosis of MUE.
Methods: Prospective, blinded, and randomized clinical trial. Dogs fulfilling the inclusion criteria were randomly allocated to receive 1 drug regimen.
Results: Four of 10 dogs in the COP group and 5/9 in the AraC group survived > 12 months but neither the survival time nor the time-to-treatment failure differed between the 2 groups. Treatment with COP resulted in an unacceptable incidence of adverse effects.
Conclusions: The adverse effects of COP make it an unsuitable treatment for MUE. Although survival of animals treated with AraC was broadly similar to that reported in recently published studies describing this treatment, it remains unclear whether it confers any benefit over using prednisolone alone.     

Nonsteroidal anti-inflammatory drugs induce hypermotilinemia and disturbance of interdigestive migrating contractions in instrumented dogs

Nonsteroidal anti-inflammatory drugs (NSAIDs) induce gastric ulcers due to inhibition of prostaglandin production. Prostaglandins have an influence on physiological gastrointestinal motility, but the relationships between NSAID-induced gastric ulcer, gastrointestinal motility and motilin are unknown. Fifteen dogs were allocated randomly to three groups in which either gelatin, meloxicam or indomethacin was administered. Fecal occult blood and gastrointestinal motility were monitored continuously for 6 days. In addition, analyses of the plasma motilin concentration, gastrointestinal endoscopy and gastric emptying, and detection of motilin cells were performed. Gastrointestinal motility was disturbed in the indomethacin group, presenting as disappearance of interdigestive migrating contractions (IMCs) 3 days before gastric ulcers were detected. Delayed gastric emptying and hypermotilinemia were observed significantly more often in the indomethacin group compared with the other groups. Motilin cell-crypt/villi ratio in the indomethacin group significantly decreased in the duodenum and jejunum, compared with the other groups. No significant changes in any tests were observed in the meloxicam group, when compared with the gelatin group. These findings suggest that the disturbance of IMCs caused by hypermotilinemia, with changes in motilin cell distribution, and delayed gastric emptying induced by indomethacin may contribute to the development of gastric ulcers.     

Pharmacokinetic analysis of mosapride following intravenous and oral administration in beagle dogs

The aim of this study was to investigate the pharmacokinetic properties of mosapride after intravenous and oral administration to beagle dogs. To obtain the advanced pharmacokinetic parameters of mosapride, both noncompartmental analysis and pharmacokinetic modeling were performed. Twenty beagle dogs were randomly sorted into intravenous (1 mg single administration of mosapride) and oral (5 mg once a day administration of mosapride) groups. Blood samples were collected according to the reported schedule for pharmacokinetics. The plasma concentration of mosapride was analyzed using liquid chromatography–tandem mass spectrometry. According to the pharmacokinetic analysis, the absorption rate of mosapride was 3.14 ± 1.14 hr⁻¹ and oral bioavailability of mosapride was approximately 1%. The one-compartment model well described the pharmacokinetics of mosapride after both intravenous and oral administration to dogs. These findings will help facilitate the determination of the optimal dose regimen of mosapride for dogs with gastrointestinal disorder.     

联合应用阿苯达唑和伊维菌素在线虫感染鄂尔多斯细毛羊体内的药动学研究

为阐明联合应用阿苯达唑(ABZ)和伊维菌素(IVM)在胃肠道线虫感染鄂尔多斯细毛羊体内的药动学互作关系,以感染胃肠道线虫的鄂尔多斯细毛羊为研究对象,比较研究了单独或联合应用阿苯达唑和伊维菌素后的药物动力学特征。通过粪便虫卵检查法,选取感染胃肠道线虫的鄂尔多斯细毛羊15只,随机分成3组,每组5只。第1组口服给予阿苯达唑(15mg/kg),第2组皮下注射伊维菌素(0.2mg/kg),第3组皮下注射伊维菌素(0.2mg/kg)的同时口服阿苯达唑(15mg/kg)。于给药后不同时间,由颈静脉采集血样,分离血浆,并用高效液相色谱法测定各时间点血浆阿苯达唑、阿苯达唑亚砜、阿苯达唑砜和伊维菌素浓度,并用PK Solution 2.0药物动力学软件计算出各药动学参数。结果表明,联合用药组绵羊血浆伊维菌素峰浓度(Cmax)、药时曲线下面积(AUC)和平均滞留时间(MRT)分别为44.80ng/mL±6.12ng/mL、5 007.46ng.h/mL±1 301.42ng.h/mL和85.47h±5.03h,均显著(P<0.05)小于单独用药组的对应参数值67.62ng/mL±9.06ng/mL、7 125.08ng.h/mL±908.52ng.h/mL和113.39h±9.00h。口服阿苯达唑组绵羊血浆中仅检测到了阿苯达唑砜和阿苯达唑亚砜,而未检测到阿苯达唑母药。联合用药后,除阿苯达唑砜的达峰时间(T max)显著推迟外,阿苯达唑砜和阿苯达唑亚砜的其他各参数之间均无显著性差异。因此,联合应用IVM和ABZ可影响它们在胃肠道线虫感染鄂尔多斯细毛羊体内的药动学特征,且对伊维菌素药动学特征的影响尤为明显,在临床联合用药过程中应予以重视。     

Clinical and histopathological features and prognosis of gastrointestinal adenocarcinomas in Jack Russell Terriers

There has been an increase in the number of Jack Russell Terriers (JRTs) diagnosed with adenomas and adenocarcinomas of the gastrointestinal tract in Japan. This study retrospectively investigated the clinical and histopathological features and prognosis of adenocarcinomas arising in the gastrointestinal tract in JRT dogs. Seven JRTs and 39 dogs of other breeds diagnosed with gastrointestinal adenocarcinoma were included in the study. The most common sites of gastrointestinal adenocarcinoma in JRTs were the pylorus and rectum. On histopathological examination, these adenocarcinomas showed a papillary or tubular growth pattern, and the lesions were confined within the mucosal epithelium and poorly invasive. Among all dogs with gastric adenocarcinoma, the median survival time (MST) for five of the JRTs could not be determined because more than half of the cases remained alive, while the MST for nine non-JRT dogs was 34 days. Among all dogs with adenocarcinoma in the large intestine, the MST for three of the JRTs could not be determined, while the MST for nine non-JRT dogs was 1,973 days. The difference in MST between JRT and non-JRT dogs with gastric adenocarcinoma was significant (P=0.0220). Since gastrointestinal adenocarcinomas in JRTs show distinct characteristics with respect to their clinical features, treatment course, and prognosis, a different surgical and medical treatment plan should be considered compared to the management of gastrointestinal adenocarcinomas in other dog breeds.     

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.