Equine veterinary journal. Supplement最新文献

Gastric ulceration is a prevalent condition of racehorses. A number of models of gastric ulceration have been described, but none mimic the conditions of a horse in training. The objectives of this study were to determine whether gastric ulcers could be induced and maintained in a group of horses in simulated race training. In addition, serum cortisol was measured on a weekly basis to investigate the possibility that stress may be important in the pathogenesis of gastric ulceration. Thirty horses used in the trial were fed Bermuda grass hay and 6 kg of a concentrate diet, and exercised 6 days/week at speed over a distance of 1.6-2.4 km. Serum was collected and gastroendoscopic examinations performed on a weekly basis for the duration of the trial. All horses developed moderate to severe ulceration, and ulcers were maintained for the 56 day period of the trial. Only one horse had signs of abdominal discomfort, which resolved with minimal symptomatic treatment and without the use of anti-ulcer medications. Serum cortisol remained within reference ranges for the duration of the trial. Although there was some variation between the weekly examinations, serum cortisol concentrations were decreased from values obtained at the start of the trial. In this study ulcers developed without the administration of nonsteroidal anti-inflammatory agents or withholding of feed. This model provides a method to study the condition, and to investigate the effects of medications on the healing of ulcers in racehorses.

Omeprazole has been shown to promote healing of spontaneously occurring gastric ulcers in horses when administered for 28 days at a dose of 4 mg/kg bwt/day and to prevent recurrence of ulcers in almost all horses when treatment is continued at a dose of at least 2 mg/kg bwt/day. The purpose of the 3 studies reported here was to 1) evaluate the evolution of potential effects of omeprazole paste (GastroGard), at a dose of 20 mg/kg bwt/day (5x the recommended dose) for 91 days in mature Thoroughbred horses; 2) evaluate the safety in young horses of omeprazole paste when dosed at 4 mg/kg bwt/day (1x), 12 mg/kg bwt/day (3x) or 20 mg/kg bwt/day (5x) for 91 days in Tennessee walking horse foals; and 3) evaluate the safety of omeprazole paste when dosed at 40 mg/kg bwt/day (10x) for 21 days in mature Thoroughbred horses. Within each study, horses were allocated randomly to the control or omeprazole paste treatment group. Clinical examinations, serum biochemistry and haematology were performed at regular intervals until necropsy at the end of the study. There were no treatment-related clinical signs in any treated horse and serum biochemistry and haematology were normal. In conclusion, omeprazole paste is safe for use in horses as demonstrated in studies with foals and mature horses.

Gastric contents were sampled in horses via nasogastric tube to determine changes in pH and bile salt concentrations during feeding and fasting periods. The horses were rotated through 4 feeding protocols. (1) hay; (2) hay with twice daily grain meals; (3) and (4) fasting preceded by either hay only or hay and grain. Sequential, hourly samples were collected from 3 horses prepared with gastric cannulas. Horses were fed hay twice daily and grain mix either twice daily or in small aliquots dispensed every 90 min. The horses were sampled during normal feeding or after 14 h of feed deprivation. Gastric pH values varied with time, but there was no significant difference between the feeding protocols or the fasting period on mean pH. Bile salt concentrations in fasted animals averaged 0.23-0.44 mmol/l with individual samples greater than 0.9 mmol/l. The bile salt concentrations in fed animals were consistently below 0.2 mmol/l. The effect of bile salt and acid on the stratified squamous gastric mucosa was tested in vitro. Mucosa, stripped of muscle and serosal layers, was mounted in Ussing chambers and the electrical potential difference (PD) across the tissue recorded. Sodium taurocholate or deoxycholate (0.3 mmol/l, bile salt) and/or HCl were added to the mucosal bathing solutions. The bile salt alone had no significant effect. Addition of acid (pH 2.5) to control tissues caused a decrease in the PD, which recovered within 20 min. Addition of acid to tissues exposed to bile salts resulted in a significant decrease in the PD, which did not recover. We conclude that combinations of bile salts and acid are more injurious to the stratified squamous gastric mucosa of the equine than acid alone. Concentrations of bile salts and acid sufficient to alter the electrolyte transport function of this mucosa can be found in the gastric contents of horses deprived of feed for as little as 14 h.

Although gastric ulcers have been identified relatively frequently in racing Thoroughbreds, there have been no large scale studies to determine their effect on health and performance. Two hundred and two Thoroughbred horses in active race training were selected by the attending veterinarians for gastro-endoscopic examination. Images of the stomach mucosa were stored in a digitised format for subsequent evaluation. The number of ulcers and a score of severity were determined. Gastric ulceration of the squamous mucosa was identified in 82% of horses. Seventy-three (39%) horses displayed clinical signs consistent with gastric ulceration. Increasing Furr and Murray Score was associated with poor hair coat (P = 0.03), colic (P = 0.03), and increasing serum creatinine concentration (P = 0.029). There were no associations between haematology and serum biochemistry values (other than serum alkaline phosphatase concentration and serum creatinine concentration) and gastric ulceration. Our study confirmed the relatively high incidence of gastric ulceration in Thoroughbred horses involved in active race training. Gastric ulceration is a potential, but rare, cause of overt colic, but may produce more subtle detrimental effects on a horse's condition. It is concluded that the diagnosis of gastric ulceration should be based on an endoscopic examination of the stomach, although future studies are required to elucidate further the aetiology and clinical significance of gastric ulceration.

The antisecretory activity of omeprazole on gastric acid when administered i.v., intragastrically or per os, was evaluated in 2 female and 3 castrated male horses. Each horse had been prepared with a chronic indwelling gastric cannula. A single i.v. administration of omeprazole (1.5 mg/kg bwt) was effective in abolishing basal and pentagastrin (PG)-stimulated acid secretion. Once daily, nasogastric administration of omeprazole in acid-stable granules for 5 days inhibited acid secretion in a dose-dependent manner: 57% (1.5 mg/kg bwt) and 98% (5.0 mg/kg bwt) reduction of PG-stimulated acid secretion. The degree of inhibition was maintained over a 19 day treatment period with once daily dosing. A prototype oral paste formulation containing either acid-stable omeprazole granules or uncoated omeprazole powder was equipotent when compared to a similar dosage of acid-stable omeprazole granules administered by nasogastric tube. A dose-dependent inhibition was seen with the oral paste formulation containing omeprazole powder: 55% (1.5 mg/kg bwt) and 77% (3.0 mg/kg bwt) reduction of PG-stimulated acid secretion after 5 days. Therefore, a paste formulation of omeprazole powder may offer an effective, easily administered, once daily acid inhibitory treatment for gastric ulcer disease in horses.

In a multicentre trial, 13 cannulated horses were treated orally once daily with a paste that delivered omeprazole at a dose of 4 and 5 mg/kg bwt in a 2-period crossover design to evaluate steady state gastric acid suppression. In each period, basal (unstimulated) and pentagastrin-stimulated gastric output were evaluated at 5-8 h after 5 doses, at 13-16 h after 10 doses, and at 21-24 h after 15 doses. Baseline data for gastric acid secretion were collected once for each horse in the month prior to initiation of omeprazole treatment. The inhibition of gastric acid secretion relative to baseline values, following treatment with omeprazole, were calculated and expressed as per cent. Pharmacokinetic data were also collected in this trial. At 4 mg/kg bwt, the oral paste formulation of omeprazole inhibited both basal and pentagastrin-stimulated gastric acid secretion by 99% at 5-8 h after treatment and by 83% (basal) and 90% (pentagastrin-stimulated) at 21-24 h. Inhibition following the administration of omeprazole at a dose of 5 mg/kg bwt was not significantly greater than when given at 4 mg/kg bwt. The results from this study could possibly lead to the development of an effective and practical antisecretory treatment of ulcer disease in horses.

The effect of intramuscular (i.m.) omeprazole (0.25 or 1.0 mg/kg bwt; LD and HD), respectively, on volume, total acid output (TAO) and pH of the gastric juice was studied during 24 h in 5 horses with a chronically implanted gastric cannula. Whether secretion in controls was basal or stimulated with pentagastrin (8 micrograms/kg bwt/h), volume (NS) and TAO (P < 0.01, NS) gradually decreased and pH increased (P < 0.05, NS). Omeprazole significantly reduced the average basal TAO by 49 +/- 6% (LD) and 88 +/- 3% (HD) and the stimulated TAO by 64 +/- 2% and 97 +/- 1%. Basal pH in controls was 2.1-4.2 and after omeprazole treatment, pH 2.8-4.1 (LD) and 2.4-6.6 (HD). After stimulation, the corresponding pH values were 2.6-3.3, 3.9-4.9 and 5.4-7.2. The biological availability of omeprazole was 70-80%. Due to the simplicity of the administration technique and the higher biological availability, intramuscular administration may offer a practical and less expensive way of treating gastric ulcers in horses.

A multicentre, blinded, randomised complete-block, field trial was conducted with 140 horses and foals age 4 weeks-28 years to determine if omeprazole paste is effective and safe in promoting healing of spontaneous gastric ulcers under a variety of field conditions and in different breeds and ages of horses. Horses in the study had gastric ulceration as determined by gastroscopy and were divided into replicates of 4 or 5 animals. One horse in each replicate was assigned randomly to receive an empty omeprazole syringe (sham-dosed control) and the remaining horses received omeprazole paste once daily for 28 days. Gastroscopy was repeated at the end of the study. Horses treated with omeprazole had significantly (P < 0.01) more improvement in ulcer scores at the end of the study compared with controls. Ulcers were improved in 32.4 and 99.0% of the control and omeprazole groups, respectively. Ulcers were completely healed in 8.9 and 86.7% of the control and omeprazole groups, respectively. Under typical field conditions, omeprazole was effective at enhancing healing of spontaneous gastric ulcers in horses of a variety of ages and breeds.