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Background: Phenylbutazone is commonly prescribed for treatment of various painful or inflammatory disorders in horses, but is associated with gastrointestinal (GI) adverse effects. Anecdotally, many practitioners prescribe omeprazole concurrently with phenylbutazone to reduce development of equine gastric ulcer syndrome (EGUS), but the efficacy and safety of this practice remains unknown., Objectives: To evaluate the effect of omeprazole on phenylbutazone-induced equine glandular gastric disease (EGGD) and equine squamous gastric disease (ESGD)., Study Design: Randomised block experimental design., Methods: Twenty-two horses with EGGD and ESGD scores ≤2 were included. Horses were assigned to treatment groups: phenylbutazone (4.4 mg/kg PO q 12 h; PBZ), phenylbutazone plus omeprazole (4 mg/kg PO q. 24 h; PBZ/OME) or placebo (CON) in a randomised block design based upon initial EGGD score. Horses were treated for up to 14 days. Gastroscopy was performed weekly; CBC and biochemistry were performed at Day 0 and study end. Horses were monitored for signs of colic and/or diarrhoea., Results: EGGD score increased in PBZ (median change 1, inter-quartile range, [IQR], 0-2) compared to PBZ/OME (median change 0, IQR -1 to 0; P = .05). PBZ/OME (6/8) had more intestinal complications than CON (0/6; difference between proportions = 75%; 95% CI, 23%-93%; P = .03). Plasma protein concentrations decreased in PBZ, compared to CON (mean difference between groups, 14 g/L; 95% CI, 1.04-27; P = .03). Five horses were withdrawn from the study due to intestinal complications (n = 3 PBZ/OME and n = 2 PBZ); one horse (PBZ) was withdrawn due to severe grade 4 EGGD., Main Limitations: Small sample size and changes in management for the 2-3 days prior to study initiation; variable treatment duration among groups due to development of complications., Conclusions: Administration of omeprazole ameliorated PBZ-induced EGGD, but was associated with an increase in intestinal complications. Caution should be exercised when co-prescribing NSAIDs and omeprazole in horses, particularly in association with change in management., (© 2020 EVJ Ltd.)

Reasons for Performing the Study: Limited data are available on the relative pharmacokinetics and pharmacodynamics of different omeprazole formulations., Objectives: To compare pharmacokinetic and pharmacodynamic effects of a novel omeprazole formulation against a currently registered product., Study Design: Masked 2 period, 2 treatment crossover., Methods: Twelve clinically healthy horses were studied over two 6-day treatment periods. Horses were randomly assigned to receive a novel omeprazole paste (Ulcershield: ULS) or a currently registered reference omeprazole product (OMO). Gastric pH was measured continuously for 10 h on the day prior to commencing treatment (Day -1) and after 6 days of oral treatment (Day 5) using in situ antimony pH probes within an indwelling nasogastric tube. Plasma pharmacokinetics were determined on Days 0 and 6., Results: Treatment significantly (P<0.005) increased gastric pH on Day 5, compared to results obtained prior to treatment (Day -1) and there was no significant difference between products (P = 0.773). Similarly, comparison of median hourly gastric pH (P = 0.593), mean gastric pH (P = 0.154), percentage time pH<4 (P = 0.259) and area under the time-gastric pH response curve (P = 0.734) did not discriminate between products. Both treatments resulted in significantly lower gastric ulcer severity scores (both P = 0.004), with no difference between treatments (P = 0.688). Comparison of mean log area under time-plasma concentration curves demonstrated that, although the lower limit of the 90% confidence interval was within the -20% limit for bioequivalence, the upper limit was exceeded, suggesting that the test product could have greater bioavailability than the reference product., Main Limitations: The small sample size, large interhorse plasma omeprazole concentrations, and low bioavailability of omeprazole impacted the sensitivity of the bioequivalence analysis., Conclusions: ULS matched or slightly exceeded OMO plasma concentrations. Both products resulted in equivalent increases in gastric pH, gastric pH profiles and decrease in gastric ulcer scores. Thus, ULS was pharmacodynamically equivalent to OMO and was associated with an equivalent beneficial effect on gastric squamous mucosal ulceration., (© 2017 EVJ Ltd.)

Reasons for Performing Study: This study investigated the use of a wireless ambulatory capsule (WAC; SmartPill(®) pH.p GI Monitoring System) to determine WAC-gastric emptying time (GET) in ponies., Objectives: To measure WAC-GET and compare it to those findings with GET assessed by nuclear scintigraphy (S-GET)., Hypothesis: WAC-GET will be slower than S-GET, but will be significantly correlated., Methods: Seven healthy adult mixed-breed pony mares were used in this study. Feed was withheld for 12 h prior to the WAC administration. After administration, a complete-feed diet was fed to allow the WAC to pass into the stomach. Luminal pH, temperature and pressure were collected by a modified receiver secured to the pony. Once the pH reached a value of ≥ 8.0, it was determined that gastric emptying had occurred, and ponies were fed grass hay. After 5 days, data were downloaded and analysed using proprietary software. During the second period of the study, after at least 2 weeks, 4 of the ponies underwent a standard S-GET test., Results: The WAC was successfully administered, and data were collected from all ponies. The mean percentage of data packets collected by the receiver was 84.9 ± 3.51% (range 66.8-95.1%). Mean WAC-GET was 7.38 h (range 0.15-46.65 h). Mean gastric pH was 4.75 (range 2.07-6.99). Mean small intestinal transit time was 4.6 h. The mean pH for the small intestine was 8.0. The mean S-GET time (in hours) when 10% of the radioactive feed is present in the stomach (T-90%) was 2.3 h. The S-GET did not correlate significantly with the WAC-GET., Conclusions and Potential Relevance: The WAC was safely administered to ponies, and data were collected using a modified receiver. The WAC-GET varied considerably between ponies, but was ≤ 3 h in 5 of the 6 ponies. The WAC used in this study provided a noninvasive technique that produced novel information about the pony gastrointestinal tract, but owing to the substantial variability in GET values and long transit time it may not be a reliable clinical tool at this time., (© 2012 EVJ Ltd.)

Reasons for Performing Study: Endotoxaemia is one of the most severe and ubiquitous disease processes in horses. Although dimethyl sulphoxide (DMSO) is used clinically in horses, there is no study indicating its efficacy in endotoxaemic horses., Hypothesis: DMSO ameliorates the clinical response to i.v. lipopolysaccharide (LPS) administration., Methods: Eighteen horses were assigned randomly to one of 4 groups: Normosol-LPS (0.2 mug/kg bwt, i.v.); DMSO (1 g/kg bwt, i.v.)-saline; high-dose DMSO (1 g/kg bwt, i.v.)LPS; low-dose DMSO (20 mg/kg bwt, i.v.)-LPS. Horses participating in the DMSO-saline group were later assigned randomly to one of the LPS groups. Data for physical parameters, white blood cell counts, plasma TNF-alpha, and blood lactate and glucose concentrations were examined for the effect of treatment using a repeated-measures mixed-model ANOVA. A value of P<0.05 was considered significant., Results: Endotoxaemia occurred in all horses receiving LPS, as indicated by the clinical score, physical parameters, haemoconcentration and leucopenia. High-dose DMSO ameliorated the effect of LPS on fever. DMSO, at either dose, but did not have a significant effect on LPS-induced changes in all other evaluated parameters., Conclusions: In this study, DMSO had minimal effects on clinical signs of induced endotoxaemia in horses. The effects were manifested by amelioration of LPS-induced fever.

Reasons for Performing Study: Volatile fatty acids, byproducts of carbohydrate fermentation by resident bacteria, have been implicated in causing nonglandular (NG) gastric ulcers. Lactic acid (LA), also produced by stomach bacteria, may cause gastric ulcers when exposed to the equine NG mucosa., Objectives: To investigate the in vitro effects of LA on equine NG mucosa bioelectric properties, sodium transport and tissue resistance., Methods: Gastric tissues obtained from 13 mature horses were studied in Ussing chambers. Short-circuit current (Isc) and potential difference (PD) were measured, and electrical resistance (R) and conductance (G) calculated for tissues after addition of HCl and LA (5, 10, 20 and 40 mmol/l) in normal Ringer's solution (NRS)., Results: Mucosa exposed to HCl or LA (5, 10 and 20 mmol/l) in NRS (pH 1.5 and to a lesser extent pH 4.0) had a significant decrease in Isc and PD. Mucosa exposed to a high concentration of LA (40 mmol/l) in NRS (LRS) at pH 1.5 showed an increased G, but this increase was not significant. Values returned to baseline after solutions were returned to pH 7.0. Histological changes were consistent with HCl-induced (pH <4.0) acid damage., Conclusions: HCl induced alteration in bioelectric properties of equine NG mucosa whereas addition of LRS did not, other than those changes seen with HCl alone.

Reasons for Performing Study: Endotoxaemia causes a disruption of gastrointestinal motility in the horse but there is no information on its effects on gastric secretion. Lipopolysaccharide (LPS) administration is known to affect gastric secretion in other species., Hypothesis: That LPS, a toxic component of Gram-negative bacteria, would reduce gastric acid secretion and that pretreatment with phenylbutazone (PBZ) would block the effects of LPS., Methods: The effects of LPS and PBZ on gastric contents were investigated in fasted, mature horses, with permanent gastric cannulae. Horses were pretreated with either saline or PBZ 15 mins before a 60 min infusion of either LPS or saline. Gastric contents were collected at 15 min intervals for 3 h, beginning 15 mins after the start of the LPS or saline infusion., Results: Lipopolysaccharide significantly decreased gastric acid output, [K+] and potassium output and increased [Na+] and sodium output. Phenylbutazone did not affect basal gastric acid secretion but decreased LPS-induced changes in the secreted volume, [Na+] and sodium output., Conclusions: This study provides evidence that LPS affects gastric acid secretion in the horse and that these LPS-induced changes are mediated, in part, by prostaglandins., Potential Relevance: Lipopolysaccharide administration can induce changes in the composition of gastric contents in the horse but further work is needed to determine the source of these changes.

Equine gastric ulcer syndrome (EGUS) represents a major health problem in performance horses. Much debate exists regarding endoscopic gastric ulcer scoring systems and their ability accurately to predict severity or depth of gastric ulcers. The purpose of this study was to evaluate the ability of an endoscopist to count gastric ulcers and predict gastric ulcer severity or depth using 2 endoscopic scoring systems and compare them to the same gastric ulcers see on necropsy and histopathology. Endoscopic examination of the stomach was performed under general anaesthesia on 23 mixed breed yearling horses, after feed was withheld for 24 h. Gastric ulcers were scored using 2 systems, number/severity-scoring (N/S) and practitioner simplified (PS) systems. After endoscopy, the horses were subjected to euthanasia and the stomach mucosa examined blindly and scored again at necropsy using above scoring systems. Representative gastric ulcers were then placed in 10% formalin and processed routinely for histopathology. The gastric ulcers were scored using a histopathology system (HSS) based on ulcer depth. Number scores in the N/S scoring system and PS on endoscopic and necropsy examinations were compared using Friedman 2 way analysis of variance. Where significant differences between variables were found a post hoc analysis was conducted using a Tukey's Studentised range (HSD) test. Severity scores using the N/S (ENGS) and PS scores recorded for the stomach via endoscopy and scores from HSS were evaluated for significant association using a Mantel-Haenszel Chi-square and Pearson moment correlation coefficient analysis. Significance was P < 0.05. All horses had gastric ulcers in the nonglandular mucosa via endoscopic examination and at necropsy examination. Mean nonglandular ulcer number (ENGN) score was significantly (P = 0.0024) lower on endoscopic examination compared to the score at necropsy (NNGN); whereas PS scores were not significantly different on endoscopy when compared to necropsy examination. A significant but weak association was found between ENGS and HSS (3.89, P = 0.048; r = 0.453, P = 0.045) and no correlation was found between PS and HSS (1.2, P = 0.272; r = 0.117; P = 0.622). Only 1/23 horses had glandular ulcers observed via endoscopic examination whereas, 6/23 horses had glandular ulcers at necropsy and on histopathology. The prevalence of EGUS is high in stalled yearling horses. The endoscopist may underestimate the number of gastric ulcers and may not be able accurately to predict the severity or depth of those ulcers present in the nonglandular equine stomach. Furthermore, the endoscopist may miss glandular gastric ulcers.

Gastric emptying was evaluated in ponies using the acetaminophen (AP) method. Fifteen minutes after i.v. administration of metoclopramide, erythromycin, yohimbine, atropine or saline, the ponies were given AP by stomach tube. Blood samples for AP analysis were collected at baseline and 15, 30, 45, 60, 75, 90, 105 and 120 min after AP administration. Time to reach peak serum concentration (Tmax), maximum serum concentration (Cmax) and area under the AP serum concentration vs. time curve (AUC) were determined for each treatment group. In the control group, Tmax was 31 min and this decreased significantly (P < 0.05) following the administration of metoclopramide. Atropine significantly increased Tmax and decreased Cmax and AUC. Yohimbine significantly increased AUC. Erythromycin did not significantly change any parameter. This study indicates that acetaminophen can be used to evaluate gastric emptying in ponies. The method is easy to perform and is minimally invasive. Metoclopramide stimulated gastric emptying of liquid in healthy, fasting ponies. Atropine significantly delayed, while erythromycin had little effect on, gastric emptying. Yohimbine increased the cumulative absorption of AP.

Five investigators familiar with gastric ulcer disease in horses met to establish a scoring system that could be utilised in future studies. Slides of gastric lesions were viewed and discussed and a scoring system established that required the nonglandular and glandular portions of the stomach to be graded separately. Each portion of the stomach (glandular and nonglandular) received a score for number of ulcers present and a score for severity of ulcers which resulted in each stomach receiving 4 separate scores. After the grading system was developed, each investigator independently graded 16 horses with gastric ulcer disease that had been previously recorded on video tape. The results of each investigator's scores were then compared. There was a variability between observers in the scores for severity of both nonglandular and glandular lesions but the variability was not significant. The variability between observers for the number of glandular lesions was also not significant. This implied that there was consistency between the 5 observers in the way severity of lesions was scored and the number of glandular lesions. However, there was a significant variability between observers for the number of nonglandular lesions which implied agreement on this observation was more variable.