In vitro effects of hydrochloric acid and various concentrations of acetic, propionic, butyric, or valeric acids on bioelectric properties of equine gastric squamous mucosa

OBJECTIVE: To compare the effects of hydrochloric acid (HCl) and various concentrations of volatile fatty acids (VFAs) on tissue bioelectric properties of equine stomach nonglandular (NG) mucosa. SAMPLE POPULATION: Gastric tissues obtained from 48 adult horses. PROCEDURES: NG gastric mucosa was studied by use of Ussing chambers. Short-circuit current (Isc) and potential difference (PD) were measured and electrical resistance (R) and conductance calculated for tissues after addition of HCl and VFAs (5, 10, 20, and 40 mM) in normal Ringer's solution (NRS). RESULTS: Mucosa exposed to HCl in NRS (pH of 1.5 and, to a lesser extent, 4.0) had a significant decrease in Isc, PD, and R, whereas tissues exposed to acetic acid at a pH of < 4.0, propionic and butyric acids at a pH of 相似文献   

Effect of hydrochloric acid,pepsin, or taurocholate on bioelectric properties of gastric squamous mucosa in horses

OBJECTIVE: To determine the effect of pH with or without pepsin or taurocholic acid on the bioelectric properties of gastric squamous mucosa in horses. SAMPLE POPULATION: Gastric tissues obtained from 16 adult horses that did not have evidence of gastric disease. PROCEDURE: Bioelectric properties of squamous mucosa were determined, using modified Ussing chambers. Tissues then were exposed to mucosal pepsin (1 mg/ml) or taurocholic acid (2.5 mM) under neutral (pH 74) or acidic (pH 1.7) conditions. RESULTS: Exposure of mucosal sheets to an acidic pH resulted in an immediate and sustained decrease in transmembrane potential difference and calculated tissue resistance. Pepsin or taurocholic acid did not significantly affect bioelectric variables when added to a mucosal bath solution of pH 7.4. A synergistic effect between pepsin or taurocholic acid and mucosal acidification was not detected. CONCLUSIONS AND CLINICAL RELEVANCE: Mucosal acidification with or without pepsin or taurocholic acid resulted in reduced tissue resistance. These data support the contention that squamous erosions or ulcers in horses are mediated, in part, by prolonged exposure of gastric squamous mucosa to luminal acid.     

Bradykinin stimulates prostaglandin E2 production and cyclooxygenase activity in equine nonglandular and glandular gastric mucosa in vitro

REASONS FOR PERFORMING STUDY: There are few data available regarding regulation of prostaglandin (PG) generation by equine gastric mucosae and the role of the cyclooxygenase (COX) isoforms in their production. OBJECTIVES: To: 1) characterise and quantify PGE2 output in vitro; 2) examine the sensitivity of PGE2 production to exogenous bradykinin (BK) exposure; 3) determine the contribution of the COX-1 and COX-2 pathways to basal and BK-stimulated PGE2 production; and 4) measure if BK influences electrogenic ion transport in equine gastric mucosae in vitro. METHODS: Full thickness gastric sheets were obtained from horses at post mortem, stripped of muscle layers and mounted in Ussing chambers. Tissues were exposed to bradykinin (BK, 0.1 micromol/l) either alone, or following pretreatment with a selective COX-2 inhibitor (NS-398, 1 micromol/l) or a nonselective COX inhibitor (piroxicam, 1 micromol/l), or were untreated. RESULTS: BK administration increased PGE2 output from the basolateral but not the apical faces of both tissue types. Piroxicam, but not NS-398, reduced basolateral PGE2 release below control levels in both tissue types. Both piroxicam and NS-398 pretreatment inhibited BK-stimulated PGE2 release. In separate experiments, BK was without effect upon electrophysiological parameters of tissues mounted in Ussing chambers. CONCLUSIONS: PGE2 is produced by the nonglandular and glandular equine gastric mucosae in vitro. Significantly more PGE2 is released basolaterally than apically. BK stimulated the production of PGE2 from the basolateral side of both tissue types. These findings suggest that COX-1 is a significant pathway for basal PGE2 production from the basolateral faces of both nonglandular and glandular equine gastric mucosae in vitro.     

Effect of paddock vs. stall housing on 24 hour gastric pH within the proximal and ventral equine stomach

REASONS FOR PERFORMING STUDY: Stall housing has been suggested as a risk factor for ulcer development in the equine stomach; however, the exact pathogenesis for this has not been established. OBJECTIVES: To investigate the effect of 3 environmental situations (grass paddock, stall alone or stall with adjacent companion) on pH in the proximal and the ventral stomach. METHODS: Six horses with permanently implanted gastric cannulae were used in a randomised, cross-over, block design. Each horse rotated through each of three 24 h environmental situations. Horses remained on their normal diet (grass hay ad libitum and grain b.i.d.) throughout the study. Intragastric pH was measured continuously for 72 h just inside the lower oesophageal sphincter (proximal stomach) and via a pH probe in the gastric cannula (ventral stomach). RESULTS: Neither proximal nor ventral 24 h gastric pH changed significantly between the 3 environmental situations. Mean hourly proximal gastric pH decreased significantly in the interval from 01.00-09.00 h compared to the interval from 13.00-20.00 h, regardless of environmental situation. Median hourly proximal pH only differed in the interval from 06.00-07.00 h compared to the interval 14.00-19.00 h. Neither mean nor median hourly ventral gastric pH varied significantly with the time of day. CONCLUSIONS: The change in housing status used in the current study did not affect acid exposure within either region of the equine stomach. The pH in the ventral stomach was uniformly stable throughout the study, while the proximal pH demonstrated a 24 h circadian pattern.     

Nutritional management of gastric ulceration

Gastric ulcers are common in horses and equine gastric ulcer syndrome describes ulcers in the distal oesophagus, nonglandular and glandular stomach as well as the proximal duodenum. Ulcers in the distal oesophagus and nonglandular region of the stomach are probably caused by hydrochloric acid, whereas ulcers in the glandular stomach and proximal duodenum are likely to be caused by a breakdown in the mucosal defence mechanisms. Regardless of the location of ulcers, initial treatment with pharmacological agents is necessary to suppress hydrochloric acid; however, nutrition and management changes are required to maintain ulcer healing and help prevent recurrence. In addition, many dietary supplements have been marketed to help maintain stomach health and some scientific data on their effects on gastric ulcer scores and gastric juice pH are presented.     

Effect of a pelleted supplement fed during and after omeprazole treatment on nonglandular gastric ulcer scores and gastric juice pH in horses

Gastric ulcers are common in horses. The purpose of this study was to test the effect of a commercially available supplement, SmartGut^® Ultra pellets (SmGU) on gastric ulcer scores and gastric juice pH after omeprazole treatment in stall‐confined horses. Eight Thoroughbred horses were studied in a 2‐period, 2‐treatment crossover design, where the SmGU (40 g, twice daily) was mixed in grain feed. Horses were stall‐confined and treated with the supplement or control for 6 weeks, consisting of 2 weeks (Days 1–14) omeprazole treatment, 2 weeks (Days 14–28) following discontinuation of omeprazole treatment, one week (Days 28–35) alternating feed deprivation to induce or worsen existing ulcers and a one week (Days 35–42) recovery period. Gastroscopy was performed and gastric juice pH measured on Days 0, 14, 28, 35 and 42. Gastric ulcer lesion number (NGN) and severity (NGS) scores were assigned to each horse by an investigator (F.M.A.) masked to treatment. On Day 0 before treatment, mean NGN and NGS scores and gastric juice pH were not different (P>0.05) between treatment groups. By Day 14, mean NGN and NGS scores decreased (P<0.05) in both treatment groups. By Days 28 and 35, mean NGN score significantly increased in the untreated control horses but not the SmGU‐treated horses. By Day 42, mean NGN and NGS scores were not different in either group and were significantly lower than Day 0. Mean gastric juice pH was higher in both groups on Day 14 as a result of omeprazole treatment when compared with other days. SmartGut^® Ultra supplement added to the feed prevented the worsening of gastric ulcer number 2 weeks after omeprazole treatment, without altering the gastric juice pH. Supplementation with SmGU might aid in protection of the nonglandular stomach from recurrence of ulcers after omeprazole treatment in stall‐confined horses undergoing intermittent feeding.     

Treatment of equine gastric impaction by gastrotomy

A 6‐year‐old Warmblood gelding was referred for treatment of a traumatic shoulder wound and while hospitalised developed a large gastric impaction which was unresponsive to medical management. Gastrotomy as a treatment for gastric impactions is rarely attempted in adult horses due to the limited surgical access to the stomach. This report describes the successful surgical treatment of the impaction by gastrotomy and management of the post operative complications encountered.     

The effects of furosemide and pentoxifylline on the flow properties of equine erythrocytes:In vitro studies

The effects of various concentrations of furosemide and pentoxifylline on equine RBCin vitro were evaluated to facilitate better understanding of the potential effects of these drugs on blood flow properties. Furosemide induced increased mean cell volume (MCV), increased RBC potassium concentration, increased whole blood viscosity, and decreased the RBC filtrability. These data indicate that furosemide may block the RBC membrane transport pathways resulting in potassium and water retention. The increase in size and the resultant decrease in the surface-area-to-volume ratio may have caused the impaired RBC filtrability and increased blood viscosity. Pentoxifylline improved RBC filtrability without changing the RBC size or the potassium or chloride concentrations, suggesting that pentoxifylline may increase the deformability of the RBC membrane. The study indicated that pentoxifylline has potential therapeutic applications for improving microvascular blood flow but that furosemide may have adverse effects on blood flow.Abbreviations cP centipoise - EIPH exercise-induced pulmonary haemorrhage - MCV mean cell volume - Na-K-2Cl sodium potassium 2-chloride - PCV packed cell volume - RBC red blood cell     

Effect of a feed/fast protocol on pH in the proximal equine stomach

Reasons for performing study: Risk factors for the development of gastric squamous ulcers include various management procedures, such as intermittent feed deprivation that can occur during weight management regimens or stall and dry lot confinement. Objectives: To investigate the effect of intermittent feed deprivation relative to continuous feed intake on proximal intragastric pH, specifically in the region of the squamous mucosa of the lesser curvature. Methods: In 6 horses, pH electrodes were placed just inside of the oesophageal sphincter in the stomach for each of two 72 h protocols (A and B) in a randomised, cross‐over design. Protocol A consisted of 12 h fed, 12 h fasted, 24 h fed and 24 h fasted, in sequence. Protocol B consisted of 72 h fed. During the fed periods of each protocol, horses had ad libitum access to coastal Bermuda hay and were fed sweet feed (1 kg, b.i.d.). Horses had ad libitum access to water at all times. Results: Proximal intragastric pH was significantly lower during protocol A, than during protocol B. However, hourly mean pH was significantly different only during the day and evening hours between protocols. During protocol B, mean proximal pH decreased significantly from 03.00 to 09.00 compared to 19.00 to 23.00 h. A moderate positive correlation of hay intake vs. proximal gastric pH could be established. Conclusions: Intermittent feed deprivation decreased proximal gastric pH in horses relative to those horses for which feed was not restricted. However, the effect was only significant when fasting occurred during the day and evening hours, as a nocturnal decrease in pH occurred simultaneously in the fed horses. Potential relevance: Episodes of daytime feed deprivation should be avoided if possible, as proximal gastric acid exposure rapidly increases during such events.     

The effect of porcine hydrolysed collagen on gastric ulcer scores,gastric juice pH,gastrin and amino acid concentrations in horses

Gastric ulcers are common in horses. The purpose of this study was to test the effect of porcine hydrolysed collagen (PHC) on gastric ulcer scores and gastric juice pH in horses. We hypothesise that PHC-administration will result in improved gastric lesion scores and act synergistically with omeprazole to improve treatment efficacy. Thoroughbred horses (n = 10) were studied in a 2-period, 2-treatment crossover design, where the PHC (45 g) was administered twice daily. Horses were treated for 56 days. Gastroscopy was performed and gastric juice pH measured on Days 0, 14, 28, 42, 49 and 56. Nonglandular gastric ulcer number (NGN) and severity (NGS) and glandular ulcer number (GN) and glandular severity (GS) scores were assigned by an investigator masked to treatment and serum gastrin and amino acid concentrations. By Day 42, 2 weeks after discontinuing omeprazole treatment, NGN and NGS scores returned to pretreatment values and serum gastrin was higher when compared to values measured on Day 28. By Day 49, after the feed-deprivation period, NGN and NGS were similar to pretreatment values. By Day 56, mean NGN score was significantly lower in PHC-treated horses, compared to controls. Mean gastric juice pH significantly increased in both groups on Day 28 and the pH was significantly (P = 0.0127) higher in the PHC-treated horses. Serum amino acid concentrations were not significantly different 2 h after feeding PHC and hydroxyproline was not detected. Serum gastrin concentration did not increase 2 h after feeding in the PHC-fed horses. The PHC fed to horses enhanced the effects of omeprazole on increased gastric juice pH, inhibited gastrin secretion after feeding and resulted in fewer nonglandular ulcers after long-term feeding (56 days) in stall-confined horses undergoing intermittent feeding.     

Prevalence of gastric ulcer syndrome in high-level endurance horses

Reasons for performing the study: Equine gastric ulcers syndrome (EGUS) prevalence studies are rare in the endurance horse and none has been carried out to date in horses competing at high level. Objectives: To determine the prevalence of EGUS in high‐level endurance horses. Methods: Thirty endurance horses competing at high level were selected and submitted to 2 gastroscopic examinations. The first gastroscopy was performed during the interseason period, and the second during the competition season within 2–3 days following a ride of 90–160 km. Data related to housing, feeding, training system as well as age, breed and gender were recorded for each horse. Results: The prevalence of squamous gastric ulcers was 48% during the interseason period (mean score 0.85 ± 0.13 on a scale from 0–4) and 93% during the competition season (mean score 1.60 ± 1.15) with a highly significant difference between the seasons (P = 0.001). Most of the lesions were situated in the squamous portion of the stomach but 33.3% of horses showed also glandular lesions. Significant influence of training and performance level on the gastric score (according to the distance of the ride preceding the second gastroscopy) was shown (P = 0.038). There was also a significant influence of housing on the gastric score (P = 0.002) showing higher scores in the horses kept totally on pasture (mean score: 2.14 ± 0.14) vs. horses housed in a mixed environment (stable + pasture, mean score: 1.43 ± 0.17). Both the pastured and (stabled + pastured) groups were receiving a grain supplement but the pastured group received a higher daily starch intake, which might explain the higher ulcer prevalence. There was no influence of age, breed or gender on the gastric scores. Conclusions: The high prevalence of gastric lesions observed in this study is probably related to the high level of training and performance of the horses examined compared to the population of horses included in the prior study. Potential relevance: This prevalence of EGUS in high‐level endurance horses is comparable to the prevalence established in racing horses. The equine veterinarians may take into consideration EGUS as a potential cause of poor performance.     

The vasomotor effects of 5-hydroxytryptamine on equine basilar arteries In vitro

The vasomotor effects of 5-hydroxytryptamine (5-HT) on isolated equine basilar arteries were studied. 5-HT induced contractions of equine basilar arteries in a concentration-dependent manner, with a pEC₅₀ value (with 95% confidence limits) of 7.35 (7.08–7.62). Similar results were obtained with endothelium-denuded basilar arteries. Contractions were not competitively inhibited by the 5-HT₂ receptor antagonist ketanserin at low concentrations of 5-HT. Conversely, at high concentrations of 5-HT, contractions were inhibited by ketanserin in a concentration-dependent manner, with a pA ₂ value of 8.91 (8.62–9.20). The 5-HT₁ and 5-HT₂ receptor antagonist methiothepin shifted the concentration-response curve of 5-HT downwards and to the right in a concentration-dependent manner. In the presence of 10^-6 mol/L ketanserin, however, methiothepin antagonized 5-HT-induced contractions competitively with a pA ₂ value of 7.95 (7.59–8.31). The 5-HT₃ receptor antagonist MDL 72222 had no effect on 5-HT-induced contractions. The findings of this study indicate that 5-HT₁ and 5-HT₂ receptors are located in equine basilar arterial smooth muscle cells, and that stimulation of these receptors results in contraction.Abbreviations CR concentration ratio - EC₅₀ concentration producing 50% of the maximal response - 5-HT 5-hydroxytryptamine - MDL 72222 1H,3,5H-tropan-3-yl-3,5-dichlorobenzoate - pA ₂ negative logarithm of the molar concentration of antagonist that produces a 2-fold rightward shift of the concentration-response curve - pEC₅₀ negative logarithm of EC₅₀ - PGF₂ prostaglandin F₂     

In vitro culture of equine respiratory mucosa explants

An in vitro model of the upper respiratory tract of the horse was developed to investigate mechanisms of respiratory diseases. Four tissues of the upper respiratory tract of three horses were collected. Explants were maintained in culture at an air–liquid interface for 96 h. At 0, 24, 48, 72 and 96 h of cultivation, a morphometric analysis was performed using light microscopy, scanning electron microscopy and transmission electron microscopy. The explants were judged on morphometric changes of epithelium, basement membrane and connective tissue. Viability was evaluated using a fluorescent Terminal deoxynucleotidyl transferase-mediated dUTP Nick End Labelling (TUNEL) staining. No significant changes in morphometry and viability of any of the explants were observed during cultivation. Hence, the in vitro model may be useful to study infectious and non-infectious diseases at the level of the equine respiratory tract, with potential application to the development of vaccines and treatments for diseases of the respiratory tract.     

The prevalence and anatomical distribution of equine gastric ulceration syndrome (EGUS) in 201 horses in Denmark

Reasons for performing study: The prevalence (up to 93% in Thoroughbred racehorses) and severity of equine gastric ulceration syndrome (EGUS) have been correlated with the type of training and associated management practices. However, there have been few reports to confirm these findings in nonracehorses in Europe. Objectives: To describe the prevalence, anatomical distribution, severity and number of gastric ulceration lesions in a population of Danish pleasure horses; and to investigate differences for groups based on age, breed type and workload. Methods: A total of 201 horses not in active race‐training, age 7 months‐27 years, were evaluated, representing 23 different stables from all 5 regions of Denmark. These horses were considered to be healthy by the owner and not on veterinary treatment for EGUS. Endoscopically observed ulcer lesion scores were based on the number present (0–4) and severity (0–5). The presence or absence of ulcers in the glandular and/or nonglandular regions of the stomach was recorded and which site the most severe ulcers were found. Results: The prevalence of EGUS severity score ≥2 was 53%. The most severe lesions were commonly observed at the margo plicatus. Although older horses were not more likely to be affected by clinically significant EGUS they were more likely to have lesions in both the glandular and nonglandular regions. Differences in location of EGUS lesions were identified in different age groups, breed types and in horses exposed to different levels of work. Conclusion and potential relevance: This study confirms that gastric ulceration can be prevalent in a group of apparently clinically normal horses, not in intensive work. Further investigation of reasons for differences in EGUS location between different populations may aid toward the development of novel preventive measures.