Effects of acetylcysteine and migration of resident eosinophils in an in vitro model of mucosal injury and restitution in equine right dorsal colon

OBJECTIVES: To evaluate the in vitro protective effects of acetylcysteine and response of resident mucosal eosinophils in oxidant-induced injury to tissues of right dorsal colon of horses. ANIMALS: 9 adult horses. PROCEDURE: Gastrointestinal mucosa was damaged in vitro with 3 mM hypochlorous acid (HOCl), with and without prior exposure to 6mM acetylcysteine. Control tissues were not exposed to HOCl or acetylcysteine. Control and damaged tissues were incubated in Krebs-Ringer-bicarbonate solution and tissue resistance measured during 240 minutes. Tissue permeability to radiolabeled mannitol was also used to assess mucosal barrier integrity. Tissues were examined by light microscopy before and after HOCl exposure and during and after incubation. RESULTS: Exposure to HOCl caused tissue damage and decreased tissue resistance. Restitution did occur during the incubation period. Eosinophils were located near the muscularis mucosae in freshly harvested tissues and migrated towards the luminal surface in response to HOCl-induced injury. Compared with tissues treated with HOCl without acetylcysteine, pretreatment with acetylcysteine prevented HOCl-induced tissue damage, changes in resistance, and histologically detectable eosinophil migration. The permeability to mannitol increased to the same extent in tissues treated with HOCl alone or with acetylcysteine and HOCl. CONCLUSIONS AND CLINICAL RELEVANCE: Eosinophils migrated toward the mucosal surface in equine colon in response to oxidant-induced damage in vitro. This novel finding could be relevant to inflammation in equine colon and a pathophysiologic feature of many colonic diseases. Acetylcysteine protected the mucosa against oxidant-induced injury and may be useful as a treatment option for various gastrointestinal tract disorders in horses.     

Use of an extracorporeal circuit to evaluate effects of intraluminal distention and decompression on the equine jejunum

OBJECTIVE: To use an extracorporeal circuit to evaluate effects of intraluminal distention on the jejunum of healthy horses. SAMPLE POPULATION: 2 jejunal segments from each of 5 horses. PROCEDURE: Jejunal segments were harvested and maintained in an extracorporeal circuit. One segment was subjected to distention (intraluminal pressure, 25 cm H2O) followed by decompression, and 1 segment was maintained without distention. The influence of distention-decompression on vascular resistance was calculated. Mucosal permeability was evaluated by measuring the clearance of albumin from blood to lumen. After distention and decompression, tissue specimens were collected for histomorphologic evaluation. In addition, the contractile response of the circular smooth muscle layer was determined following incubation with 3 prokinetic agents. RESULTS: Intestinal vascular resistance increased during intraluminal distention and returned to baseline values after decompression. Albumin clearance rate increased after distention, compared with baseline and control values. Histologic examination of the distended segments revealed grade-1 and -2 lesions of the mucosal villus. Edema and hemorrhage were evident in the submucosa and muscular layers. Mesothelial cell loss, edema, and hemorrhage were also evident in the serosa. Mucosal surface area and villus tip height decreased and submucosal volume increased in the distended tissue. Compared with responses in control specimens, distention decreased the contractile response induced by cisapride, erythromycin, and metoclopramide. CONCLUSIONS AND CLINICAL RELEVANCE: Intraluminal distention of the jejunum followed by decompression increased mucosal permeability and injury and decreased responses to prokinetic agents. Horses with intraluminal intestinal distention may have a decreased response to prokinetic agents.     

Effect of a novel solution for organ preservation on equine large colon in an isolated pulsatile perfusion system

REASONS FOR PERFORMING STUDY: Several therapeutic agents have been tested in models of ischaemia and reperfusion injury (IRI) in equine jejunum, with mixed results. This study was based on the use of an organ perfusion solution (OPS) designed to protect human allografts from IRI. HYPOTHESIS: A modified OPS can preserve the integrity of equine large colon during 12 h of isolated pulsatile perfusion, in the absence of oxygen and blood. METHODS: Segments of large colon were removed from anaesthetised horses, the contents removed and the mucosa rinsed with 0.9% saline. Experimental segments were perfused for 12 h with one litre modified OPS (n = 7) delivered by pulsatile flow through an extracorporeal circuit. Control segments (n = 4) were perfused on the same circuit with one litre of autologous blood. Vascular resistance, flow and pressure were measured serially, and aliquots of OPS and blood drawn hourly for routine biochemical analyses. Mucosal biopsies of the experimental and control segments were taken at 0, 6 and 12 h and in vivo mucosal tissue at 0 h for baseline comparison. All biopsies underwent histomorphometric analysis and immunohistochemical assessment of calprotectin activity. RESULTS: All colon segments were machine perfused without technical complications. Vascular and biochemical indices remained constant over 12 h in the OPS group, and were constant over 6 h in the control group, but deteriorated later. Mucosal integrity, expression of cyclooxygenases-1 and -2, and expression of mucosal calprotectin were unchanged in the OPS group compared with the baseline tissues, and mucosal integrity was superior to the control tissues. CONCLUSIONS: A modified OPS designed to target specific pathways of damage from IRI can preserve colonic mucosal integrity for 12 h in the absence of blood and oxygen.     

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.     

In vitro investigation of the effect of prostaglandins and nonsteroidal anti-inflammatory drugs on contractile activity of the equine smooth muscle of the dorsal colon, ventral colon, and pelvic flexure

OBJECTIVES: To determine the in vitro effect of prostaglandin E2 (PGE2), PGF2alpha, PGI2; and nonsteroidal anti-inflammatory drugs (NSAID; ie, flunixin meglumine, ketoprofen, carprofen, and phenylbutazone) on contractile activity of the equine dorsal colon, ventral colon, and pelvic flexure circular and longitudinal smooth muscle. ANIMALS: 26 healthy horses. PROCEDURE: Tissue collected from the ventral colon, dorsal colon, and pelvic flexure was cut into strips and mounted in a tissue bath system where contractile strength was determined. Incremental doses of PGE2, PGF2alpha,, PGI2, flunixin meglumine, carprofen, ketoprofen, and phenylbutazone were added to the baths, and the contractile activity was recorded for each location and orientation of smooth muscle. RESULTS: In substance P-stimulated tissues, PGE2 and PGF2alpha enhanced contractility in the longitudinal smooth muscle with a decrease or no effect on circular smooth muscle activity. Prostaglandin I2 inhibited the circular smooth muscle response with no effect on the longitudinal muscle. The activity of NSAID was predominantly inhibitory regardless of location or muscle orientation. CONCLUSIONS AND CLINICAL RELEVANCE: In the equine large intestine, exogenous prostaglandins had a variable effect on contractile activity, depending on the location in the colon and orientation of the smooth muscle. The administration of NSAID inhibited contractility, with flunixin meglumine generally inducing the most profound inhibition relative to the other NSAID evaluated in substance P-stimulated smooth muscle of the large intestine. The results of this study indicate that prolonged use of NSAID may potentially predispose horses to develop gastrointestinal tract stasis and subsequent impaction.     

Effects of flunixin meglumine or etodolac treatment on mucosal recovery of equine jejunum after ischemia

OBJECTIVE: To examine the effects of flunixin meglumine and etodolac treatment on recovery of ischemic-injured equine jejunal mucosa after 18 hours of reperfusion. ANIMALS: 24 horses. PROCEDURE: Jejunum was exposed to 2 hours of ischemia during anesthesia. Horses received saline (0.9% NaCl) solution (12 mL, i.v., q 12 h), flunixin meglumine (1.1 mg/kg, i.v., q 12 h), or etodolac (23 mg/kg, i.v., q 12 h). Tissue specimens were obtained from ischemic-injured and nonischemic jejunum immediately after ischemia and 18 hours after recovery from ischemia. Transepithelial electric resistance (TER) and transepithelial flux of tritium-labeled mannitol measured mucosal permeability. Denuded villous surface area and mean epithelial neutrophil count per mm2 were calculated. Western blot analysis for cyclooxygenase (COX)-1 and -2 was performed. Pharmacokinetics of flunixin and etodolac and eicosanoid concentrations were determined. RESULTS: Ischemic-injured tissue from horses treated with flunixin and etodolac had significantly lower TER and increased permeability to mannitol, compared with that from horses treated with saline solution. Epithelial denudation after ischemia and 18 hours after recovery was not significantly different among treatments. Both COX-1 and -2 were expressed in ischemic-injured and nonischemic tissues. Ischemia caused significant upregulation of both COX isoforms. Eicosanoid concentrations were significantly lower in tissues from flunixin and etodolac-treated horses, compared with that from horses treated with saline solution. CONCLUSIONS AND CLINICAL RELEVANCE: Flunixin and etodolac treatment retarded recovery of intestinal barrier function in jejunal mucosa after 18 hours of reperfusion, whereas tissues from horses treated with saline solution recovered baseline values of TER and permeability to mannitol.     

In vitro evaluation of intraluminal factors that may alter intestinal permeability in ponies with carbohydrate-induced laminitis

OBJECTIVES: To study the in vitro effects of cecal contents incubated with corn starch on colonic permeability in horses. ANIMALS: 4 healthy adult ponies. PROCEDURE: Mucosal specimens were obtained from the right ventral colon and mounted in Ussing chambers. Changes in short circuit current, conductance, and large-molecule permeability in response to addition of cecal contents and cecal contents incubated with corn starch were evaluated for 120 minutes. RESULTS: Incubation of cecal contents with corn starch for 8 hours resulted in a decrease in cecal content pH and an increase in lactic acid concentration. These changes were similar to those reported in vivo for ponies given corn starch. Exposure of colonic mucosa to cecal contents incubated with corn starch resulted in an increase in tissue conductance and permeability of technetium Tc 99m pentetate, compared with mucosa exposed to cecal contents alone. CONCLUSIONS AND CLINICAL RELEVANCE: In vitro exposure of colonic mucosa to cecal contents incubated with starch resulted in increased paracellular permeability. Fermentation of excessive amounts of carbohydrate in the intestinal lumen of horses may directly induce increased intestinal permeability associated with carbohydrate-induced laminitis.     

Use of an isolated intestinal circuit to evaluate the effect of ischemia and reperfusion on mucosal permeability of the equine jejunum

OBJECTIVES: To evaluate the efficacy of an isolated perfusion circuit and the effect of ischemia-reperfusion on mucosal permeability of the jejunum. STUDY DESIGN: In vitro study of intestinal mucosal permeability. ANIMALS: Twelve healthy adult horses. METHODS: A control segment of jejunum was placed in an isolated perfusion circuit for 240 minutes and mucosal permeability was measured. After detecting no deleterious effects of the isolated system on the control intestine, low flow ischemia was created in experimental segments for 20, 40, 60 and 90 minutes followed by 60 minutes of reperfusion and mucosal permeability was evaluated. At the completion of the studies, histologic evaluation was used to determine mucosal grades, surface area, and volume. RESULTS: Control tissue was maintained in the isolated circuit for 240 minutes without effect on mucosal grade, surface area, or volume relative to intact tissue. After ischemia-reperfusion, mucosal grade increased, and volume and surface area decreased progressively with longer periods of ischemia. Mucosal clearance of albumin remained constant during 240 minutes of perfusion in control tissue and was elevated after ischemia-reperfusion. CONCLUSIONS: No deleterious changes were noted in jejunum perfused with this isolated circuit, whereas alterations in mucosal permeability were present after ischemia-reperfusion. CLINICAL RELEVANCE: The isolated perfusion circuit successfully maintained an isolated segment of jejunum within physiologic limits, and can be used to evaluate the effects of injury and the efficacy of pharmaceuticals to attenuate these changes.     

In vitro anion transport alterations and apoptosis induced by phenylbutazone in the right dorsal colon of ponies

OBJECTIVES: To study the functional and structural responses of the right dorsal colon (RDC) of ponies to phenylbutazone (PBZ) in vitro at a concentration that could be achieved in vivo. ANIMALS: 8 adult ponies. PROCEDURE: Short circuit current and conductance were measured in mucosa from the RDC. Tissues incubated with and without HCO3- were exposed to PBZ, bumetanide, or indomethacin. Bidirectional Cl- fluxes were determined. After a baseline flux period, prostaglandin E2 (PGE2) was added to the serosal surfaces and a second flux period followed. Light and transmission electron microscopy were performed. RESULTS: Baseline short circuit current was diminished significantly by PBZ and indomethacin, and increased significantly after addictions of PGE2. After PGE2 was added, Cl- secretion increased significantly in tissues in HCO3- -free solutions and solutions with anti-inflammatory drugs, compared with corresponding baseline measurements and with control tissues exposed to PGE2. Bumetanide did not affect baseline short circuit current and Cl- fluxes. The predominant histologic change was apoptosis of surface epithelial cells treated with PBZ and to a lesser extent in those treated with indomethacin. CONCLUSIONS AND CLINICAL RELEVANCE: Prostaglandin-induced Cl- secretion appeared to involve a transporter that might also secrete HCO3-. Both PBZ and indomethacin altered ion transport in RDC and caused apoptosis; PBZ can damage mucosa through a mechanism that could be important in vivo. The clinically harmful effect of PBZ on equine RDC in vivo could be mediated through its effects on Cl- and HCO3- secretion.     

Effects of cyclooxygenase inhibitors flunixin and deracoxib on permeability of ischaemic-injured equine jejunum

REASONS FOR PERFORMING STUDY: Recent studies have shown that flunixin prevented recovery of equine jejunum post ischaemia. However, the use of a purported cyclooxygenase (COX)-2 preferential inhibitor, etodolac, also prevented recovery. These findings may have implications for the use of nonsteroidal anti-inflammatory drugs in colic patients. OBJECTIVE: To compare the effects of deracoxib, a highly selective canine COX-2 inhibitor, with flunixin on in vitro recovery of ischaemic-injured equine jejunum. METHODS: Six horses underwent 2 h jejunal ischaemia, after which mucosa was mounted in Ussing chambers and recovered for 240 mins. Transepithelial electrical resistance (TER) and mucosal-to-serosal fluxes of 3H-mannitol were monitored as indices of barrier function in the presence of flunixin or deracoxib. RESULTS: The TER of ischaemic-injured tissue recovered significantly over 240 mins in the presence of no treatment, but not in the presence of flunixin or deracoxib. In addition, flunixin-treated ischaemic jejunum was significantly more permeable to mannitol when compared with untreated tissue by the end of the recovery period, whereas deracoxib treatment did not increase permeability. Addition of the PGE1 analogue misoprostol to flunixin-treated tissue restored recovery of TER. CONCLUSIONS AND POTENTIAL RELEVANCE: Treatment of horses with ischaemic jejunal disease with flunixin may result in a prolonged permeability defect in recovering mucosa. Addition of misoprostol or replacement of flunixin with deracoxib may ameliorate effects of COX inhibitors on recovering mucosa.     

Investigation of the effect of black walnut extract on in vitro ion transport and structure of equine colonic mucosa

OBJECTIVE: To examine the secretory response (in the presence and absence of prostaglandin inhibition) in vitro and structural alterations of colonic mucosa in horses after intragastric administration of black walnut extract (BWE). ANIMALS: 14 adult horses. PROCEDURE: Seven horses were administered BWE intragastrically and monitored for 11 hours. Tissue samples were obtained from the right ventral, left ventral, and right dorsal colons (RVC, LVC, and RDC, respectively) of the 7 BWE-treated and 7 control horses. Tissue samples were examined via light microscopy, and the extent of hemorrhage, edema, and granulocytic cellular infiltration (neutrophils and eosinophils) was graded. Colonic mucosal segments were incubated with or without flunixin meglumine (FLM) for 240 minutes; spontaneous electrical potential difference and short-circuit current (Isc) were recorded and used to calculate mucosal resistance. RESULTS: Colonic tissues from BWE-treated horses (with or without FLM exposure) had an overall greater Isc during the 240-minute incubation period, compared with tissues from control horses. The resistance pattern in RVC, LVC, and RDC samples (with or without FLM exposure) from BWE-treated horses was decreased overall, compared with control tissues (with or without FLM exposure). Histologically, colonic mucosal tissues from BWE-treated horses had more severe inflammation (involving primarily eosinophils), edema, and hemorrhage, compared with tissue from control horses. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, BWE administration appears to cause an inflammatory response in colonic mucosal epithelium that results in mucosal barrier compromise as indicated by decreased mucosal resistance with presumed concomitant electrogenic chloride secretory response, which is not associated with prostaglandin mediation.     

Mucosal distribution of eosinophilic granulocytes within the gastrointestinal tract of horses

OBJECTIVES: To establish reference values for the range of the number of eosinophils found in equine gastrointestinal mucosa and to describe the distribution of this cell within the equine gastrointestinal mucosa. SAMPLE POPULATION: Gastrointestinal mucosal specimens from 14 adult horses euthanatized for reasons other than gastrointestinal disease. PROCEDURES: Gastrointestinal mucosal specimens were collected and grouped according to their anatomic regions. For histologic examination slides were stained with Luna's eosinophil stain to determine eosinophil accumulation and distribution. The mucosa was divided into 5 sections for each anatomic location, and the percentage of eosinophils in each of the 5 sections relative to the total eosinophil count in all sections was determined. Additionally, the number of eosinophils per square millimeter of mucosa was calculated as a measure of the degree of eosinophil accumulation. RESULTS: Lowest numbers of eosinophils were found in the stomach, and numbers increased from there to the cecum, then decreased from the ascending colon (right ventral colon, left ventral colon, pelvic flexure, left dorsal colon, and right dorsal colon) to small colon. In all gastrointestinal sections, most eosinophils were located near the muscularis mucosae and were rarely found near or on the luminal surface of the mucosa. CONCLUSIONS AND CLINICAL RELEVANCE: The distribution of eosinophils in the gastrointestinal tract of horses followed a pattern within the mucosa and between different sections of the gastrointestinal tract. The derived reference values and distribution data could be used to detect changes in eosinophil response in the equine gastrointestinal mucosa caused by diseases states.     

Effects of carprofen on the integrity and barrier function of canine colonic mucosa

OBJECTIVE: To measure effects of carprofen on conductance and permeability to mannitol and histologic appearance in canine colonic mucosa. SAMPLE POPULATION: Colonic mucosa from 13 mature mixed-breed dogs. Procedures-Sections of mucosa from the transverse colon and proximal and distal portions of the descending colon were obtained immediately after dogs were euthanized. Sections were mounted in Ussing chambers. Carprofen (400 microg/mL) was added to the bathing solution for treated sections. Conductance was calculated at 15-minute intervals for 240 minutes. Flux of mannitol was calculated for three 1-hour periods. Histologic examination of sections was performed after experiments concluded. Conductance was graphed against time for each chamber, and area under each curve was calculated. Conductance X time, flux of mannitol, and frequency distribution of histologic findings were analyzed for an effect of region and carprofen. RESULTS: Carprofen significantly increased mean conductance X time, compared with values for control (untreated) sections for all regions of colon. Carprofen significantly increased mean flux of mannitol from period 1 to period 2 and from period 2 to period 3 for all regions of colon. Carprofen caused a significant proportion of sections to have severe sloughing of cells and erosions involving >or= 10% of the epithelium, compared with control sections. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen increased in vitro conductance and permeability to mannitol in canine colonic mucosa. Carprofen resulted in sloughing of cells and erosion of the colonic mucosa. These findings suggested that carprofen can compromise the integrity and barrier function of the colonic mucosa of dogs.     

Effects of oligosaccharides on functional parameters of the intestinal tract of growing pigs.

Feeding experiments were carried out in growing pigs using topinambur powder or inactivated yeasts as prebiotic additives with an application period of at least 3 weeks. At the end of the experimental periods the animals were killed and segments of the intestinal tract were used for measuring transport physiological parameters and for mucin histochemistry. Jejunal epithelia were mounted in Ussing chambers for measuring electrical tissue parameters, paracellular permeability and short circuit current response to mucosal glucose. Both prebiotics had no effects on basal or forskolin stimulated short circuit currents. Total tissue conductances tended to be higher in response to both prebiotics. Topinambur increased mucosal-to-serosal fluxes of mannitol in the proximal and distal jejunum, which could only be demonstrated for the distal jejunum when inactivated yeasts were fed. Mucosal application of glucose induced higher current responses in jejunal tissues. From histochemistry it could be demonstrated that both prebiotics increased the number of ileal goblet cells and the thickness of the colonic mucosa.     

In vitro effects of nonsteroidal anti-inflammatory agents and prostaglandins I2, E2, and F2alpha on contractility of taenia of the large colon of horses.

OBJECTIVES: To determine the in vitro effect of various prostaglandins (PG) and nonsteroidal anti-inflammatory drugs (NSAID) on contractile activity of the large-colon taenia of horses. ANIMALS: 14 healthy horses. PROCEDURE: The taenia was collected from the ventral colon, cut into strips (2 X 10 mm), and mounted in a tissue bath system (20-ml capacity) that contained oxygenated Krebs buffer solution warmed to 37.5+/-0.5 C. After equilibration, incremental doses of PGE2, PGF2alpha, PGl2, flunixin meglumine, carprofen, ketoprofen, and phenylbutazone were added to the baths, and contractile activity was recorded. Magnitude of the response was calculated by comparing contractile activity before and after administration of the PG or NSAID to the tissue baths. RESULTS: PGE2 and PGF2alpha, caused a significant increase in contractile activity, whereas PGI2 induced an inhibitory response. Activity of NSAID on contraction was predominantly inhibitory. At low concentrations, ketoprofen induced an excitatory effect, which then became inhibitory at high concentrations. Compared with the other NSAID, carprofen significantly reduced contractile activity at lower concentrations. CONCLUSIONS: PGE2 and PGF2alpha appear to enhance contractility of large-colon taenia of horses, whereas PGI2 was inhibitory in the in vitro model. Administration of NSAID also inhibited contractility, with carprofen having the most potent effect. CLINICAL RELEVANCE: Administration of NSAID in combination with liberation of endogenous PG may predispose horses to development of intestinal stasis and subsequent impaction.     

Short-Term Effects of Duodenocecostomy on Body Weight,Glucose Absorption,Serum Components,and Intestinal Histopathology in Four Normal Horses

The objective of this study was to evaluate duodenocecostomy in horses performed through a ventral midline laparotomy and report its influence on body weight, glucose absorption, serum components, and characteristics of jejunum, cecum, and large colon histology. Four horses were submitted to the duodenocecostomy technique through a ventral midline laparotomy with animals in dorsal recumbency under inhalation anesthesia, followed by abdominal exploration. A side-to-side anastomosis was performed between the duodenojejunal flexure and the base of the cecum with two simple continuous suture lines of the serosal and muscular layers. The size of the opening created was approximately 2 cm in diameter. The mucosa layer was not sutured. After 30 days, animals were submitted to a second laparotomy to check the patency of the duodenocaecal fistula. During both laparotomy procedures, excisional biopsies of different segments of the gastrointestinal tract were performed. Information on physical examination findings, results of hematologic and histopathologic evaluations, and oral glucose absorption test were recorded. The horses did not have significant weight loss from baseline, and absorption curve of glucose did not significantly vary from baseline. Only triglycerides had significant alterations. Histologic evaluation of jejunum, cecum, and large colon did not show alterations of intestinal structure and morphology. We concluded that the proposed technique, principally in relation to the fistula size and not suturing the mucosa layer, allowed partial or total occlusion of the fistulae without the necessity of a second surgery and avoided the permanent bypass of ingesta and weight loss.     

Nonsteroidal anti‐inflammatory drug associated right dorsal colitis in the horse

Right dorsal colitis in horses is a disease characterised by mucosal ulceration and oedema that is localised to the right dorsal colon. It is considered one of the more severe adverse effects associated with the use of nonsteroidal anti‐inflammatory drugs (NSAIDs), particularly phenylbutazone. Diagnosis is typically made based on a history of NSAID administration, the presence of hypoproteinaemia and hypoalbuminaemia, as well as ultrasound evidence of thickening and oedema of the right dorsal colon wall. Definitive diagnosis is made at surgery or necropsy. Treatment involves discontinuation of NSAID therapy, dietary management, and mucosal protectants such as misoprostol and sucralfate. Prognosis is dependent upon early recognition and appropriate treatment. Horses on prolonged courses of NSAIDs should have frequent monitoring of serum total protein and albumin concentrations, as this is one of the earliest and most consistent clinicopathological findings.     

Effects of ischemia and the cyclooxygenase inhibitor flunixin on in vitro passage of lipopolysaccharide across equine jejunum

OBJECTIVE: To determine whether ischemia and flunixin affect in vitro lipopolysaccharide (LPS) absorption in samples of the jejunum of horses. ANIMALS: 12 horses. PROCEDURE: Horses were anesthetized, a midline celiotomy was performed, and the jejunum was located. Two 30-cm sections of jejunum (60 cm apart) were selected. One segment was designated as control tissue; ischemia was induced in the other segment for 120 minutes. Horses were then euthanatized. Mucosa from each jejunal segment was mounted on Ussing chambers and treated with or without flunixin. Tissues from 6 horses were used to assess permeability to radiolabeled LPS; mucosal samples from the remaining 6 horses were incubated with fluorescent-labeled LPS (FITC-LPS) and examined histologically. Production of tumor necrosis factor-alpha (TNF-alpha) and production of LPS-binding protein (LBP) were assessed as indicators of mucosal response to LPS. RESULTS: Ischemia significantly increased mucosal permeability to LPS, but by 180 minutes, the mucosa was not more permeable than control tissue. Flunixin treatment adversely affected intestinal barrier function throughout the experiment but did not result in increased mucosal permeability to LPS. Compared with control tissues, LBP production was increased by ischemia and reduced by exposure to LPS. In ischemic tissue, FITC-LPS entered the lamina propria but TNF-alpha was produced on the mucosal side only, indicating little response to the absorbed LPS. CONCLUSIONS AND CLINICAL RELEVANCE: Ischemia increased LPS passage across equine jejunal mucosa. Flunixin delayed mucosal recovery but did not exacerbate LPS absorption. Evaluation of the clinical importance of flunixin-associated delayed mucosal recovery requires further in vivo investigation.     

Salmonella Antimicrobial Activity of Selected Strains of Enterolactobacillus Species Isolated from the Gastrointestinal Tract of the Horse

The gastric mucosa and the mucosa of the right and left dorsal colon were biopsied in each of the 15 horses, and a total of 45 samples were collected. Mucosal samples were cultured using a Lactobacillus enrichment broth. While numerous Lactobacillus strains were identified, Lactobacillus reuteri was the most common organism identified. Sixteen strains of Lactobacillus reuteri were selected for antimicrobial testing. Salmonella antimicrobial activity was identified in six out of 16 strains tested. Organisms with Salmonella antimicrobial activity were cultured from the stratified squamous epithelium of the stomach and the mucosa of the right and left dorsal colon.     

Medical Management of Right Dorsal Colitis in 5 Horses: A Retrospective Study (1987–1993)

Right dorsal colitis in horses has been associated with administration of phenylbutazone. Although reports of right dorsal colitis in this species have described surgical treatment associated with a poor prognosis, we have had success treating this condition medically. This report describes 5 horses with right dorsal colitis confirmed during celiotomy that were initially managed medically. All horses had a history of intermittent abdominal pain; weight loss was noted in only 1 horse. The doses (2.0 to 4.6 mg/kg PO bid) and duration (5 to 30 days) of administration of phenylbutazone were not unusually high relative to those recommended (4.4 mg/kg PO bid). Hypoproteinemia and hypoalbuminemia were observed in all horses at the time of admission; packed cell volume was low in 4 horses, and hypocalcemia was also observed in 4 horses. Three of 5 horses (60%) appeared to respond to dietary management and discontinuation of administration of nonsteroidal anti-inflammatory drugs. Dietary management consisted of feeding pelleted feed, and restricting or eliminating roughage for a period of at least 3 months. Two horses developed strictures of the right dorsal colon. One horse that developed a colonic stricture, possibly because its owners did not comply with recommendations for management, was subsequently treated surgically. The remaining horse that developed a stricture of the right dorsal colon was euthanized. These data indicate that some horses with right dorsal colitis can be successfully managed with medical treatment.