The effects of phenylbutazone on the morphology and prostaglandin concentrations of the pyloric mucosa of the equine stomach

Phenylbutazone, a nonsteroidal anti-inflammatory drug known to produce gastric ulcers, was administered intravenously (13.46 mg/kg body weight) daily to 12 horses. Horses were euthanatized daily after 24, 48, 72, and 96 hours following the initial injection. Eight untreated horses served as controls. Small multifocal pyloric erosions were seen after 24 hours and then progressed in severity over time. The erosions were characterized by sloughing of the surface epithelium, subepithelial bleb formation, necrosis of the lamina propria, degeneration of the walls of subsurface capillaries, and microthrombosis of the capillaries of the pyloric mucosa. Large numbers of neutrophils with abundant fibrin and cellular debris were present at the erosion sites. Eroded pyloric mucosa and adjacent macroscopically intact mucosa were examined ultrastructurally. In both the macroscopically eroded mucosa and multifocally in the adjacent macroscopically uneroded mucosa, there was cellular swelling of the endothelium, pericytes, and smooth muscle cells of arterioles. In capillaries and post-capillary venules, the endothelium ranged from swollen to lysed and necrotic. Extensive extravasation of erythrocytes and edema were seen. These lesions were not seen in the control horses. Phenylbutazone produces a microvascular injury that is associated with the formation of pyloric erosions in horses. The pyloric mucosa of six horses was assayed for prostacyclin and prostaglandin E2 at 48 and 96 hours following the initial injection. There was no statistically significant difference between prostaglandin concentrations in the mucosa of control and treated horses. It was concluded that there was little correlation between pyloric mucosal prostaglandin concentrations and pyloric erosions after 48 hours.     

Histological characteristics of induced acute peptic injury in equine gastric squamous epithelium.

The objective of the study reported here was to characterise the microscopic appearance of peptic-injured equine gastric squamous epithelium in relation to the duration of peptic injury. Erosions and ulcers were induced in equine gastric squamous epithelium using a feed deprivation protocol that results in prolonged increased gastric acidity. Specimens of normal gastric mucosa and mucosa with lesions created after 48 and 96 h of feed deprivation were compared for characteristics associated with angiogenesis and mucosal proliferation. Fifteen mature horses, 9 geldings and 6 mares, age 3-20 years, were divided into 3 groups. Group 1 (n = 5) had normal-appearing gastric squamous mucosal epithelium and had been killed due to problems unrelated to the gastrointestinal tract. Groups 2 (n = 5) and 3 (n = 5) had lesions induced in the gastric squamous epithelium by alternating 24 h periods of feed deprivation and ad libitum access to hay, for totals of 48 and 96 h feed deprivation, respectively. Following lethal injection of barbiturate, stomachs were removed and fixed by filling with 4-6 l 10% buffered formalin. Sections were made from lesions in the gastric squamous epithelium adjacent to the margo plicatus along the right side of the stomach/greater curvature and the lesser curvature. Measurements of total epithelial thickness, keratinised epithelium, nonkeratinised epithelium, epithelial projections, capillary extension into the epithelium and lamina propria thickness were made. The cross-sectional areas of arterial and venous vascular structures in the lamina propria at the lesions and their margins were measured using image analysis software. All horses, except one, in Group 2 developed erosions or ulcers in the gastric squamous epithelium after feed deprivation. There were several changes in the epithelium adjacent to erosions and ulcers, compared to normal epithelium, from horses in Groups 2 and 3: total epithelial thickness was significantly (P<0.05) greater, including both keratinised and nonkeratinised layers in most specimens; the length of epithelial projections and extent to which capillaries from the lamina propria extended toward the luminal surface, and the cross-sectional area of vascular structures (arterioles, capillaries, venules) in the lamina propria were significantly greater. Epithelial thickness of erosion beds was not significantly less than normal epithelium, although a greater proportion of the epithelium in erosions consisted of epithelial projections (Group 1, 23%; Group 2, 76%; Group 3, 72%). The cross-sectional area of vascular structures in the lamina propria beneath erosions was significantly greater than in normal mucosa only in Group 2 tissues, whereas in the lamina propria of ulcers it was significantly greater than in normal mucosa only in Group 3 tissues. The epithelial proliferation and increased vascular cross-sectional area in the lamina propria associated with peptic-induced gastric lesions are consistent with processes associated with the initiation of ulcer healing, and these changes temporally coincided with the initiation of peptic insult to the gastric squamous epithelium. These findings demonstrate that processes that promote ulcer healing begin soon after peptic injury and that they progress even with repeated peptic injury. Furthermore, our findings support observations that gastric ulcers often heal without medical intervention, and the theory that medications that reduce gastric acidity do not initiate healing, but rather facilitate ulcer healing by providing a microenvironment that is optimal for healing to proceed.     

Experimentally induced phenylbutazone toxicosis in ponies: description of the syndrome and its prevention with synthetic prostaglandin E2

Phenylbutazone (PBZ) toxicosis was induced in 9 ponies to further define the clinical and pathologic changes occurring with this syndrome. Six additional ponies were treated with PBZ and a synthetic prostaglandin E2 to determine the role of prostaglandins in the pathogenesis of PBZ toxicosis. Ponies given only PBZ exhibited CNS depression, anorexia, weight loss, diarrhea, cyanotic mucous membranes, and oral ulcers. Total serum protein concentration gradually decreased during the 10-day treatment period. Marked mucosal atrophy, focal erosions, and ulcers characterized the lesions in the alimentary tract. Ponies given PBZ and prostaglandin E2 remained clinically healthy and did not develop hypoproteinemia or mucosal atrophy. A few erosions were seen, but ulcers were not observed. The results of the present study indicate that mucosal atrophy is a characteristic lesion of PBZ toxicosis. It is also evident that inhibition of prostaglandin synthesis has an important role in the development of this syndrome.     

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.     

Studies on the pathogenesis of swine dysentery. I. Characterization of the lesions in colons and colonic segments inoculated with pure cultures or colonic content containing Treponema hyodysenteriae.

Swine dysentery was induced in pigs and in ligated colonic segments by inoculation of pure cultures of, or colonic contents containing, Treponema hyodysenteriae. The mildest changes, best seen in ligated segments 48 or 72 hours after inoculation, were congestion and leucocytic margination in mucosal capillaries and depletion of mucigen from goblet cells lining the base of the crypts of Lieberkühn. Superficial mucosal necrosis and crypt cell hyperplasia were later changes. Perfusion studies with India ink did not demonstrate occlusive mucosal ischemia in acute swine dysentery. Mucosa with lesions of swine dysentery contained at least 10(5) colony forming units of T. hyodysenteriae per gram. Mucosa without lesions had 10(5) or fewer T. hyodysenteriae per gram. Segments with acute swine dysentery were distended with clear mucoid fluid with electrolyte composition indicative of net colonic secretion. No increase in the concentration of volatile fatty acids was detected in content from intact colons or colonic segments with lesions of acute swine dysentery.     

Effects of phenylbutazone, indomethacin, prostaglandin E2, butyrate, and glutamine on restitution of oxidant-injured right dorsal colon of horses in vitro

OBJECTIVE: To study the effects of phenylbutazone, indomethacin, prostaglandin E2 (PGE2), glutamine, and butyrate on restitution of oxidant-injured right dorsal colon of horses in vitro. SAMPLE POPULATION: Right dorsal colon from 9 adult horses euthanatized for reasons other than gastrointestinal tract disease. PROCEDURES: Mucosal segments from the right dorsal colon were injured via exposure to HOCl and incubated in Ussing chambers in solutions containing phenylbutazone, indomethacin, indomethacin and PGE2, glutamine, and butyrate. Transepithelial resistance and mucosal permeability to mannitol were measured, and all mucosal segments were examined histologically. RESULTS: The HOCl-injured mucosa had lower resistance and higher permeability to mannitol, compared with control tissue. Histologic changes were also evident. Resistance of HOCl-injured mucosa recovered partially during the incubation period, and glutamine improved recovery. Phenylbutazone and indomethacin increased resistance, but these increases were not significant. Butyrate and PGE2 had no effects, compared with nontreated HOCl-injured tissues. Mucosal permeability to mannitol was lower in glutamine-treated tissue, compared with nontreated tissue. Histologic changes reflected the resistance and permeability changes. CONCLUSIONS AND CLINICAL RELEVANCE: According to our findings, phenylbutazone and indomethacin do not seem to interfere with restitution of oxidant-injured mucosa of equine colon in vitro, and glutamine could facilitate mucosal restitution.     

Cyclooxygenase expression and prostanoid production in pyloric and duodenal mucosae in dogs after administration of nonsteroidal anti-inflammatory drugs

OBJECTIVE: To assess cyclooxygenase (COX) expression and prostanoid concentrations in pyloric and duodenal mucosae of dogs after administration of nonsteroidal anti-inflammatory drugs (NSAIDs). ANIMALS: 8 healthy dogs. PROCEDURES: Each dog received carprofen (4.4 mg/kg, q 24 h), deracoxib (2 mg/kg, q 24 h), aspirin (10 mg/kg, q 12 h), and placebo (1 dog treat, q 24 h) orally for 3 days (4-week interval between treatments). Before study commencement (baseline) and on day 3 of each treatment, pyloric and duodenal mucosal appearance was assessed endoscopically and biopsy specimens were obtained for histologic examination. Cyclooxygenase-1 and COX-2 protein expressions were assessed via western blotting, and prostanoid concentrations were measured via ELISAs. An ANOVA was used to analyze data. RESULTS: Treatments had no effect on mucosal appearance and ulceration was not evident histologically. In pyloric and duodenal mucosae, COX-1 expression was unaffected by treatments. Cyclooxygenase-2 expression remained unchanged in pyloric mucosa; in duodenal mucosa, aspirin significantly increased COX-2 expression, compared with effects of deracoxib and carprofen. At baseline, total prostaglandin and thromboxane B2 concentrations in pyloric mucosa were significantly greater than those in duodenal mucosa. Aspirin significantly decreased both prostanoid concentrations in both mucosal tissues, compared with other treatments. In pyloric mucosa, carprofen administration significantly decreased total prostaglandin and thromboxane B2 concentrations, compared with deracoxib administration. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, prostanoid synthesis was greater in pyloric mucosa than it was in duodenal mucosa. Nonselective NSAIDs significantly decreased prostanoid concentrations in these mucosae, compared with the effects of a selective COX-2 NSAID.     

Distribution of epidermal growth factor receptor (EGFr) in normal and acute peptic-injured equine gastric squamous epithelium.

Growth factors are important in healing and restoration of injured gastrointestinal tissues and, therefore, we characterised temporally the distribution and density of epidermal growth factor receptor (EGFr) in normal and peptic-injured gastric squamous epithelium of horses. Lesions were induced in the equine gastric squamous epithelium using a feed deprivation protocol that results in prolonged increased gastric acidity. Fifteen mature horses, 9 geldings and 6 mares, age 3 to 20 years, were used and divided into 3 groups: Group 1 (n = 5) were subjected to euthanasia for problems unrelated to the gastrointestinal tract and had normal-appearing gastric squamous mucosal epithelium; Groups 2 (n = 5) and 3 (n = 5) had lesions induced in the gastric squamous epithelium by alternating 24 h periods of feed deprivation and ad libitum access to hay, for a total of 48 h and 96 h, respectively. Following lethal injection of a barbiturate, stomachs were removed and fixed by filling with 4- 6 l 10% buffered formalin. Sections were made from normal stomachs and lesions in the gastric squamous epithelium adjacent to the margo plicatus along the right side of the stomach/greater curvature and the lesser curvature. A modified avidin-biotin immunoperoxidase technique was used to stain the formalin-fixed tissue specimens for EGFr. A computerised image analysis system was used to measure area occupied by EGFr (EGFr area) and mean EGFr density in 4 zones within the epithelium extending from the basal cell layers toward the lumen. Measurements were made of epithelium in an erosion bed, at the margin of an ulcer or erosion, and 10-15 mm distant from the lesion margin. Additionally, EGFr area and density were measured in epithelial cells adjacent to capillaries in the epithelium. Intermittent feed deprivation resulted in erosion and ulceration of the gastric squamous epithelium of each horse. Mean EGFr area and density were greatest (P<0.05) in the basal layer of epithelia from all horses, and EGFr staining diminished progressively toward the lumen. Tissues from Group 3 had significantly greater EGFr area in the lesion margin than epithelia from Group 2. EGFr density was less in the epithelia of erosion beds from Groups 2 and 3 compared to normal epithelium, and EGFr area in Group 2 erosion bed epithelia was significantly less than in normal epithelium and epithelia of Group 3. EGFr area in cells adjacent to epithelial capillaries of Group 3 was significantly greater than that of Group 1. Mitotic cell activity was significantly greater in epithelia associated with ulcers and erosions in Groups 2 and 3 compared to normal tissues from Group 1 horses. Staining for EGFr in the glandular mucosa adjacent to squamous epithelium at the margo plicatus was inconsistent and typically faint when present. EGFr distribution in equine gastric squamous epithelium was greatest in regions of greatest cell proliferation, and these areas were in the basal layers of epithelium and immediately adjacent to capillaries. There was evidence that EGFr is induced in peptic-injured equine gastric squamous epithelium. A receptor ligand, EGF or transforming growth factoralpha, may be a factor in healing of gastric squamous mucosal ulcers in horses. Further research should be directed at identifying this ligand and determining its origin in equine gastric mucosa.     

Comparative healing of mesenteric and antimesenteric incisions in the bovine jejunum

Paired incisions (n = 6 pairs) were made in the jejunum of each of 8 Holstein cows. Pairs consisted of 2-cm transverse incisions, 35 cm apart, at the antimesenteric region and at the mesenteric region. Bursting-wall tension was used to test mechanical strength, and cellular and vascular events of healing were evaluated using histologic examination and microangiography. Healing was evaluated at postoperative hour (POH) 48 in 4 of the cows (group 1) and at POH 96 in the remaining 4 (group 2). Evidence of leakage of intestinal contents was not found in any of the cows. At POH 48 and 96, bursting-wall tension was significantly (P less than 0.001) greater in the intestinal segments with antimesenteric incisions than in those segments with mesenteric incisions. Disruption of normal vasculature was seen at mesenteric and antimesenteric sites; ingrowth of vessels, reformation of vascular plexuses, and development of collateral circulation were observed at POH 96. Granulation tissue was observed at POH 96 at the antimesenteric and mesenteric sites, and early stages of mucosal reepithelialization were seen in several sections at POH 48. Better apposition of tissue layers was seen in antimesenteric incisions, but mucosal eversion was evident in several mesenteric incisions. Some sections examined from cows at POH 96 had complete bridging of mucosa, submucosa, and muscularis layers at the antimesenteric location. Inflammatory cells were observed along the incision and at the mucosal and serosal surfaces in many of the sections. Deposition of new collagen was not appreciable in any section at POH 48 or 96.     

Vascular Injury Associated with Naturally Occurring Strangulating Obstructions of the Equine Large Colon

Ten horses were euthanatized before, during, or after surgery to correct severe volvulus of the large colon. At surgery, the colonic serosa changed from blue-gray, blue or purple toward a more normal pink in seven horses after the volvulus was corrected. The mucosa consistently remained black or dark red. Results of postmortem colonic microangiography revealed perfusion of the serosa and the circular and longitudinal muscle layers, but mucosal perfusion was limited by thrombosis in the muscularis mucosae and submucosa. There was evidence of thrombosis of the mesenteric colic vessels in six horses. Damage to the colonic vascular system, especially thromboembolism in the submucosa, may be an important limitation to colonic viability after surgical correction of volvulus of the large colon.     

Orally administered phenylbutazone causes oxidative stress in the equine gastric mucosa

Phenylbutazone (PBZ) is widely used in equine medicine, and its side effects on the gastrointestinal tract are well known. The inhibition of prostaglandins and the oxidative stress induced by nonsteroidal anti‐inflammatory drugs (NSAIDs) are described as mechanisms of gastric mucosal injury in humans. In horses, only the secondary effect of changes in cyclooxygenases is related to gastric mucosal injury. The objective of this study was to evaluate the effect of PBZ on certain antioxidative/oxidative parameters of the gastric mucosa. The concentrations of antioxidants and oxidants (superoxide dismutase, SOD; catalase, CAT; nitric oxide, NO; total glutathione, GSH; myeloperoxidase, MPO; and malondialdehyde, MDA), PGE₂ levels, and the ulcerative lesions score were assessed. The results demonstrated decreased levels of antioxidant variables, increased levels of oxidant variables, and alterations in the prostaglandin E₂ (PGE₂), myeloperoxidase (MPO), and glutathione (GSH) levels. In conclusion, PBZ induces oxidative stress in the gastric glandular mucosa of horses by changing the antioxidant–oxidant balance of this surface, which might be regarded as another mechanism of injury in the horse stomach.     

Effect of Platelet-Activating Factor Antagonist L-691,880 on Low-Flow Ischemia-Reperfusion Injury of the Large Colon in Horses

Objective—To determine the effect of platelet-activating factor (PAF) antagonist L-691,880 on low-flow ischemia and reperfusion (I-R) of the large colon in horses. Animals —12 adult horses. Experimental Design—Horses were anesthetized, and the large colon was exteriorized through a ventral median celiotomy and instrumented. Colonic arterial blood flow was reduced to 20% of baseline (BL) and maintained for 3 hours; flow was then restored, and the colon was reperfused for 3 hours. One of two solutions was administered intravenously 30 minutes before reperfusion: group 1, 10 mL/kg 0.9% NaCl; and group 2, 5 mg/kg PAF antagonist L-691,880 in 0.9% NaCl. Hemodynamic variables were monitored and recorded at 30-minute intervals. Systemic arterial and colonic venous blood were collected for measurement of blood gas tensions, oximetry analyses, packed cell volume, and total plasma protein concentrations. Colonic venous blood was collected for determination of lactate, 6-keto prostaglandin F_1α (6-kPG), prostaglandin E₂ (PGE₂), and thromboxane B₂ (TXB₂) concentrations. Full-thickness biopsy specimens were harvested from the left ventral colon for histological evaluation. Results—There were no significant differences between the two groups for any hemodynamic or metabolic variables. Colonic venous pH decreased, and carbon dioxide tension and lactate concentration increased during ischemia but returned to BL values during reperfusion. Colonic venous 6-kPG concentration was significantly increased above BL value at 2 hours and remained increased through 6 hours in horses of both groups. Colonic venous PGE₂ concentration was significantly greater in group 2 compared with group 1 throughout the study. Colonic venous PGE₂ concentration was increased above BL value from 3 to 6 hours in horses of both groups. Colonic venous TXB₂ concentration was not different between groups but was significantly increased above the BL value for the first hour of reperfusion. Low-flow I-R of the large colon caused significant mucosal necrosis, hemorrhage, edema, and neutrophil infiltration; however, there were no differences in histological variables between vehicle-control and PAF antagonist-treated horses. Conclusion—No protective effects of PAF antagonist L-691,880 were observed on colonic mucosa associated with low-flow I-R. Additionally, deleterious drug-induced effects on hemodynamic and metabolic variables and colonic mucosal injury were not observed.     

Chronic gastroenterocolitis in nine cats.

Lesions of a chronic gastroenterocolitis were found in 9 cats of the Persian breed that were euthanized after a prolonged period of bloody diarrhea. Gross lesions consisted of gastrointestinal edema with prominent Payer's patches, multiple grayish nodules, and a few irregular erosions within the colonic mucosa. Microscopically, the changes were composed of degeneration, necrosis, and proliferation of gastric glandular epithelium, dilated intestinal crypts with lymphoplasmacytic cell infiltration of the lamina propria, and in 1 cat, severe transmural necrosis of the colon. With the Giemsa stain, spiral-shaped organisms in the gastrointestinal lumen and intracellularly in the gastric and the colonic epithelium were observed. These organisms could not be cultured. Although the role of these spiral-shaped organisms was not determined, other agents that could explain the disorder were not found.     

Histopathological and ultrastructural changes in simulated large colonic torsion and reperfusion in ponies.

This investigation examines the histological and ultrastructural lesions of the colonic mucosa during terminal experimental infarction and subsequent reperfusion. Four ponies were anaesthetised and subjected to surgical torsion of the colon. Biopsies were collected at hourly intervals for 3 h, at which point the torsions were corrected. Circulation was re-established for 2 h and the bowel was re-biopsied at hourly intervals. The ponies were killed while under anaesthesia. During the 3 h experimental infarction, the bowel became macroscopically thickened and dark purple. Histologically, the mucosa degenerated from Grade 0 to Grade 3. Ultrastructurally, there was progressive micro-vascular distension with erythrodiapedesis and damage to the interstitial cells. Spaces developed between the bases and sides of the columnar epithelial cells and sloughing followed subsequently. During the 2 h reperfusion interval, the mucosa continued to degenerate rapidly to a Grade 5, and was characterised by extensive interstitial damage, oedema, cellular swelling, necrosis and mitochondrial damage. The results showed that the experimentally infarcted colonic mucosa degenerated sequentially. Following circulatory reestablishment, continued rapid mucosal degeneration characteristic of reperfusion injury occurred. Reperfusion injury is probably responsible, at least in part, for the often poor outcome of infarcted bowel in horses following surgical correction.     

Studies on the pathogenesis of Salmonella typhimurium and Salmonella choleraesuis var kunzendorf infection in weanling pigs

Twenty-six 4-week-old pigs were randomly allotted to 4 groups: group 1--orally inoculated with Salmonella typhimurium; group 2--orally dosed with S choleraesuis; and groups 3 and 4, with surgically constructed intestinal loops--loops inoculated with either S typhimurium or S choleraesuis. One pig each from groups 1 and 2 was killed at 8, 12, 24, 48, 72, 96, and 120 hours after inoculation. One pig each from groups 3 and 4 was killed at 2, 4, 6, 8, 12, and 24 hours after intestinal loop inoculation. Inoculation of S typhimurium resulted in acute enterocolitis of variable severity, whereas inoculation of S choleraesuis resulted initially in septicemia followed by formation of large necrotic and ulcerative lesions in the colonic mucosa. The most consistent systemic lesion of S choleraesuis infection was interstitial pneumonia and multifocal hepatic necrosis. Salmonella typhimurium and S choleraesuis were ultrastructurally within enterocytes of ligated ileal loops. Intracellular bacteria were morphologically intact, occurred free in the cytoplasm and membrane bound, and caused no detectable cytotoxic effect to the cell. Both S typhimurium and S choleraesuis penetrated the intestinal mucosa and were isolated from mesenteric lymph nodes at 2 hours after inoculation.     

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.     

Microvascular circulation of the ascending colon in horses

Microvascular circulation of the ascending colon in healthy horses was studied using microangiography, light microscopy, and scanning electron microscopy. The pelvic flexure with 30 cm of ventral and dorsal colon attached was removed from 14 adult horses immediately after horses were euthanatized. The lumen was flushed with warm water, and this section of the ascending colon was placed in a 37-C bath of isotonic NaCl. In sections from 8 horses, colic vessels were perfused with a radio-opaque medium for microangiography. After angiographic evaluation, tissue sections were prepared for light microscopic observation, using standard histologic methods. In sections from 6 horses, injection replicas were made by perfusing the vessels with 2 types of plastics. The results of microangiography, light microscopy, and scanning electron microscopy of vascular replicas were correlated, providing a comprehensive documentation of the microvasculature of the ascending colon at the pelvic flexure. Arteries branched from mesenteric colic vessels approximately every 2 cm toward the colonic tissue. Immediately after branching, arterial vessels formed an anastomotic plexus, the colonic rete. However, each branch from the colic vessel eventually continued into the colonic tissue. A second set of vessels originated from the colonic tissue. A second set of vessels originated from the colonic rete and supplied the mesenteric lymph nodes. Arterial vessels penetrated the tunica muscularis into the submucosa 3 to 4 cm toward the antimesenteric border forming a submucosal vascular network. From the submucosal arterioles, branching took place at right angles to supply the mucosal capillaries. Capillaries surrounded the colonic glands and anastomosed at the luminal surface, forming a superficial luminal honeycomb-appearing vascular plexus.(ABSTRACT TRUNCATED AT 250 WORDS)     

ULTRASONOGRAPHIC APPEARANCE OF CANINE PARVOVIRAL ENTERITIS IN PUPPIES

The ultrasonographic appearance of the gastrointestinal tract of puppies suffering from parvoviral enteritis was characterized. Forty puppies between 6 and 24 weeks of age with confirmed canine parvoviral enteritis were examined ultrasonographically within 24 h of admission. Sonographic findings included fluid‐filled small intestines in 92.5% of subjects, and stomach and colon in 80% and 62.5% of subjects, respectively. Generalized atony was present in 30 subjects and weak peristaltic contractions indicative of functional ileus observed in the remaining 10 subjects. The duodenal and jejunal mucosal layer thicknesses were significantly reduced when compared with normal puppies with mean duodenal mucosal layer measuring 1.7 mm and jejunal mucosal layer 1.0 mm. Additionally, a mucosal layer with diffuse hyperechoic speckles was seen in the duodenum (15% of subjects) and the jejunum (50% of subjects). The luminal surface of the duodenal mucosa was irregular in 22.5% of subjects and the jejunal mucosa in 42.5% of subjects. In all of these subjects, changes were accompanied by generalized indistinct wall layering. Small intestinal corrugations were seen within the duodenum in 35% of subjects and within the jejunum in 7.5%. A mild amount of anechoic free peritoneal fluid was observed in 26 subjects and was considered within normal limits and a moderate amount of anechoic free peritoneal fluid was observed in six subjects. The jejunal lymph node size was within normal limits. None of the above changes are pathognomonic for canine parvoviral enteritis but finding them in combination is highly suggestive.     

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.     

Morphologic alterations observed during experimental ischemia of the equine large colon

Morphologic changes that develop sequentially in the large colon during experimentally induced ischemia were documented in 14 halothane-anesthetized horses. Colonic ischemia was induced by 4 types of vascular occlusion, 24 cm proximal and distal to the pelvic flexure. The effect of transmural (colonic wall) vascular compression combined with either venous occlusion (3 horses, group A) or venous and arterial occlusion (3 horses, group B) of the colonic vessels was studied for 1, 2, and 6 hours of occlusion. Also observed was the effect of reperfusion for 0.5 hour after release of the clamps for the 1- and 2-hour occlusions and for 1 hour after release of the clamps for the 6-hour occlusion. Effects of occluding only the colonic veins (4 horses, group C), or the colonic veins and arteries (4 horses, group D) were studied for 0.5, 1, 1.5, and 2 hours of occlusion and during reperfusion for 0.5 hour. Full-thickness intestinal biopsy specimens were obtained from the antimesenteric border of the pelvic flexure at 0, 0.25, 0.5, 0.75, 1, 1.5, and 2 hours during occlusion and at 0.5 hour after release of vascular occlusion. Biopsy specimens were obtained at hourly intervals from the 2 horses in which 6-hour occlusion was performed and at 1 hour after release of vascular occlusion. Macroscopic changes (serosal color, mucosal color, serum leakage) in the colon were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)