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Abstract

Objective—To determine expression of cyclooxygenase (COX) genes 1 and 2 (also called prostaglandin-endoperoxide synthases 1 and 2) and stability of housekeeping gene expression during low-flow ischemia and reperfusion in the jejunum of horses.

Animals—5 healthy adult horses.

Procedures—Horses were anesthetized, and two 30-cm segments of jejunum were surgically exteriorized. Blood flow was maintained at baseline (untreated) values in 1 (control) segment and was decreased to 20% of baseline (low-flow ischemia) for 75 minutes, followed by 75 minutes of reperfusion, in the other (experimental) segment. Biopsy samples were collected from experimental segments at baseline (T0), after 75 minutes of ischemia (T1), and after 75 minutes of reperfusion (T2); samples were collected from control segments at T0 and T2. Horses were euthanized 24 hours after induction of ischemia (T3), and additional samples were collected. Samples were evaluated histologically. Total RNA was extracted; expression of COX genes and stability of 8 housekeeping genes were determined via quantitative real-time PCR assays.

Results—COX-1 and COX-2 genes were constitutively expressed in baseline samples. Low-flow ischemia resulted in significant upregulation of COX-2 gene expression at each subsequent time point, compared with baseline values. The most stably expressed reference genes were β-actin and hypoxanthine phosphoribosyltransferase, whereas glyceraldehyde 3-phosphate dehydrogenase and β-2 microglobulin were the least stably expressed.

Conclusions and Clinical Relevance—Low-flow ischemia resulted in upregulation of COX-2 gene expression in the jejunum of horses. Housekeeping genes traditionally used as internal standards may not be stable in this tissue during arterial low-flow ischemia and reperfusion.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To assess gene expressions of cyclooxygenase-1 and -2 in oral, glandular gastric, and urinary bladder mucosae and determine the effect of oral administration of phenylbutazone on those gene expressions in horses.

Animals—12 healthy horses.

Procedures—Horses were allocated to receive phenylbutazone or placebo (6 horses/group); 1 placebo-treated horse with a cystic calculus was subsequently removed from the study, and those data were not analyzed. In each horse, the stomach and urinary bladder were evaluated for ulceration via endoscopy before and after experimental treatment. Oral, glandular gastric, and urinary bladder mucosa biopsy specimens were collected by use of a skin punch biopsy instrument (oral) or transendoscopically (stomach and bladder) before and after administration of phenylbutazone (4.4 mg/kg, PO, q 12 h) in corn syrup or placebo (corn syrup alone) for 7 days. Cyclooxygenase-1 and -2 gene expressions were determined (via quantitative PCR techniques) in specimens collected before and after the 7-day treatment period and compared within and between groups. Prior to commencement of treatment, biopsy specimens from 7 horses were used to compare gene expressions among tissues.

Results—The cyclooxygenase-1 gene was expressed in all tissues collected. The cyclooxygenase-2 gene was expressed in the glandular gastric and bladder mucosae but not in the oral mucosa. Cyclooxygenase gene expressions were unaffected by phenylbutazone administration.

Conclusions and Clinical Relevance—Cyclooxygenase-2 was constitutively expressed in glandular gastric and bladder mucosae but not in the oral mucosa of healthy horses. Oral administration of phenylbutazone at the maximum recommended dosage daily for 7 days did not affect cyclooxygenase-1 or -2 gene expression.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics, pharmacodynamics, and safety of zoledronic acid in horses.

Animals—8 healthy horses.

Procedures—A single dose of zoledronic acid (0.057 mg/kg, IV) was administered during a 30-minute period. Venous blood was collected at several time points. Zoledronic acid concentration in plasma was measured by liquid chromatography–tandem mass spectrometry, and pertinent pharmacokinetic parameters were determined. Plasma was analyzed for total calcium, BUN, and creatinine concentrations and a marker for bone resorption (C-terminal telopeptides of type I collagen).

Results—Zoledronic acid was safely administered IV during a 30-minute period, and no adverse effects were observed. Plasma concentrations of zoledronic acid were consistent with a 2-compartment mammillary model. Plasma concentrations of zoledronic acid were detected for up to 8 hours after administration. Mean total calcium concentrations in plasma were less than the reference range 7 days after zoledronic acid administration. A marker for bone remodeling decreased in concentration after zoledronic acid administration and remained low for the 1-year duration of the study. No changes in BUN and creatinine concentrations were observed after zoledronic acid administration.

Conclusions and Clinical Relevance—Zoledronic acid was safely administered in healthy horses. Zoledronic acid is reported as the strongest bisphosphonate presently available, and studies evaluating potential benefits of zoledronic acid in horses with orthopedic conditions are warranted.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the response to neostigmine of the contractile activity of the jejunum and pelvic flexure and the effects of a continuous rate infusion (CRI) of neostigmine in horses.

Animals—7 adult horses and tissue from 12 adult horses.

Procedures—A CRI of neostigmine (0.008 mg/kg/h) or placebo was administered to 6 horses in a crossover study design. Gastric emptying was evaluated by the acetaminophen test. The frequency of defecation and urination and the consistency and weight of feces were recorded throughout the experiment. The effect of neostigmine on smooth muscle contractile activity was evaluated in tissues from the jejunum and pelvic flexure. The effect of neostigmine and acetylcholine after incubation with muscarinic receptor antagonists (atropine and DAU 5884) and an acetylcholinesterase inhibitor (edrophonium) was also investigated in vitro.

Results—No difference was observed between neostigmine and placebo for time to reach peak plasma acetaminophen concentration and absorption rate constant. A CRI of neostigmine increased fecal production and frequency of urination. Neostigmine induced a dose-dependent increase of contractile amplitude in jejunum and pelvic flexure muscle strips. Incubation of muscle strips with atropine and DAU 5884 inhibited the response to acetylcholine and neostigmine. Incubation of smooth muscle strips from the jejunum with edrophonium increased the response to acetylcholine and had no effect on the response to neostigmine in vitro.

Conclusions and Clinical Relevance—A CRI of neostigmine increased fecal production and urination frequency in horses. A CRI of neostigmine did not decrease gastric emptying. Neostigmine stimulated contractile activity of jejunum and pelvic flexure smooth muscle strips in vitro.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effect of ranitidine on gastric emptying in horses.

Animals—11 adult horses.

Procedures—In vitro, isolated muscle strips from the pyloric antrum and duodenum of 5 horses were suspended in baths and attached to isometric force transducers. Once stable spontaneous contractions were observed, ranitidine or diluent was added at cumulative increasing concentrations. Isometric stress responses were compared. In vivo, 6 horses were assigned to a group in a prospective randomized crossover study design with a wash-out period of 2 weeks between trials. Ranitidine (2.2 mg/kg) or saline (0.9% NaCl) solution was administered IV, and 15 minutes later, acetaminophen (20 mg/kg), diluted in 400 mL of water, was administered via nasogastric tube to evaluate the liquid phase of gastric emptying. Serum acetaminophen concentration was measured at several time points for 3 hours by use of liquid chromatography tandem mass spectrometry. Frequency of defecation was recorded during the 3 hours of the study.

Results—Ranitidine increased the contractile activity of the pyloric antrum smooth muscle at a concentration of 10−4 M. No significant effect of ranitidine on plasma kinetics of acetaminophen was identified. Frequency of defecation did not differ between groups.

Conclusions and Clinical Relevance—Ranitidine did increase gastric motility in vitro, but no effect on liquid phase gastric emptying was identified in healthy horses by use of the acetaminophen absorption model. Results do not support the use of ranitidine to promote gastric emptying.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics and effects of the morphine antagonist N-methylnaltrexone (MNTX) on gastrointestinal tract function in horses when administered alone and in combination with morphine.

Animals—5 healthy adult horses.

Procedures—Horses were treated with MNTX (1 mg/kg, IV), and serial blood samples were collected for determination of drug pharmacokinetics. For evaluation of effects on the gastrointestinal tract when administered alone, MNTX was administered at a dosage of 0.75 mg/kg, IV, twice daily for 4 days. For evaluation of effects when administered concurrently with morphine, MNTX (0.75 mg/kg, IV, q 12 hours) and morphine (0.5 mg/kg, IV, q 12 hours) were administered for 6 days. Gastrointestinal variables evaluated were defecation frequency, weight of feces produced, fecal moisture content, intestinal transit time, and borborygmus scores.

Results—The time-concentration data for MNTX disposition best fit a 2-compartment model with a steady-state volume of distribution of 244.6 ± 21.8 mL/kg, t1/2 of 47.04 ± 11.65 minutes, and clearance of 11.43 ± 1.06 mL/min/kg. Adverse effects were not observed at doses ≤ 1 mg/kg. Administration of MNTX increased daily fecal weight. When administered concurrently with morphine, MNTX partially prevented the effects of morphine on the gastrointestinal tract by increasing defecation frequency, fecal weight, fecal moisture content, and borborygmus score, and by preventing increases in intestinal transit time.

Conclusions and Clinical Relevance—Because MNTX does not cross the blood-brain barrier, administration of the drug should not alter the analgesic effects of opioids and may attenuate the adverse gastrointestinal effects associated with use of opioids in horses.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of an external nasal dilator strip on cytologic characteristics of bronchoalveolar lavage (BAL) fluid in racing Thoroughbreds.

Design—Clinical trial.

Animals—23 Thoroughbred racehorses in active training.

Procedure—Each horse raced on 2 occasions: once while wearing an external nasal dilator strip and once while not. Bronchoalveolar lavage was performed 12 to 18 hours after each race, and BAL fluid was analyzed for RBC and leukocyte counts and hemosiderin content.

Results—Mean ± SEM count of RBCs in BAL fluid when horses raced without the nasal dilator strip (84.6 ± 27.5 cells/µL) was not significantly different from count when they raced with it (41.7 ± 12.2 cells/µL). Horses were grouped as having mild or severe bleeding on the basis of RBC count in BAL fluid after horses raced without the nasal dilator strip. Mean count when horses with severe bleeding raced without the nasal dilator strip (271.0 ± 63.7 cells/µL) was significantly higher than mean count when these horses raced with the strip (93.8 ± 37.6 cells/µL). Mean count of lymphocytes in BAL fluid was significantly lower after horses raced with the external nasal dilator strip.

Conclusions and Clinical Relevance—Results suggest that use of an external nasal dilator strip in Thoroughbred racehorses may decrease pulmonary bleeding, particularly in horses with severe exerciseinduced pulmonary hemorrhage. ( J Am Vet Med Assoc 2004;224:558–561)

Full access
in Journal of the American Veterinary Medical Association

Summary

Medical records of 245 horses that had been evaluated by use of abdominal radiography between January 1990 and December 1992 were reviewed. One hundred forty-one horses subsequently had a postmortem examination or surgical exploration performed for definitive lesion diagnosis. The signalment, diagnosis, site, and number of enteroliths were obtained from the medical records. Radiographs were evaluated individually by 3 reviewers for the presence of enteroliths, preferred diagnostic view, evidence of large colon tympany, and film quality. Of the 141 cases reviewed, 66.7% (94/141) had confirmed enterolithiasis. Enteroliths were identified in the right dorsal colon of 59 horses, in the transverse colon of 28, in the small colon of 24, and in the ventral colon of 1 (enteroliths were detected in multiple sites in 12 horses). For the 3 reviewers, mean sensitivity was 76.9% and specificity was 94.4%. Mean positive-predictive value was 96.4%, and negative-predictive value was 67.5%. Cases involving only large colon enteroliths were correctly diagnosed 83.2% of the time, compared with 41.6% of the time for cases involving small colon enteroliths. Enteroliths were evident in 54.8% of the horses with radiographic signs of large colon distention. Fifteen horses had enteroliths in the small colon, 4 in the transverse colon, and 4 in the dorsal colon.

Radiographic quality was evaluated and scored as adequate (0), underexposed (−1), overexposed (1), or incomplete. Mean score was −0.5, and there were 21 (14.9%) incomplete studies. For the 75 cases correctly diagnosed via abdominal radiography, there were 14 (18.7%) incomplete studies and a mean score of −0.43. Of the 19 false-negative evaluations, there were 3 (15.8%) incomplete studies and a mean score of −0.69. The most common error leading to the missed diagnoses seemed to be inadequate penetration of the abdomen.

Free access
in Journal of the American Veterinary Medical Association

Summary

Effects of intraluminal distention (25 cm of H2O, 120 minutes) and subsequent decompression (60 minutes) on intramural vascular patterns of the small intestine was evaluated in 7 anesthetized horses. Intraluminal distention (25 cm of H2O, 120 mintutes) was created in 2 jejunal segments in each horse. Experimental and control segments were removed either immediately after the experimental period or after 60 minutes of decompression. The vascular system of experimental and control jejunal segments was lavaged with NaCl, then was injected with a blue-colored radiopaque medium for microangiography or with a diluted methyl methacrylate for scanning electron microscopy of microcorrosion vascular casts. After angiographic evaluation, tissue sections were prepared for light microscopic evaluation to assess vascular filling and tissue morphology. The distended segments had short villi, which were separated by expanded crypts, and had mesothelial cell loss, neutrophil infiltration, and edema in the seromuscular layer. The number of perfused vessels was significantly (P < 0.05) decreased in the seromuscular layer and, to a lesser extent, in the mucosal layer of the distended segments, compared with controls. After decompression, the morphologic lesions progressed in mucosal and serosal layers and the number of observed vessels increased in all intramural layers; however, vascular density did not return to the predistention state. These results identify altered intramural vascular patterns in the equine jejunum during luminal distention and subsequent decompression.

Free access
in American Journal of Veterinary Research

Summary

Intramural vascular patterns of the jejunum and colon were evaluated during ischemic strangulation obstruction (iso, 70 minutes) and subsequent reperfusion (60 minutes) in 7 adult anesthetized horses. Microvasculature of experimental and control segments was described by comparison of results from microangiography, light microscopy, and scanning electron microscopy of vascular replicas. Experimental and control segments with isolated vascular arcades were removed either immediately after the experimental period or after 60 minutes of reperfusion. Blood was flushed from the vascular system by use of isotonic NaCl, and the segments were divided. Half of each segment was perfused with a modified radiopaque medium for microangiographic evaluation, and half was perfused with dilute methylmethacrylate to create a vascular replica to be studied by scanning electron microscopy. Microangiographic section also were evaluated for histologic changes.

Microvasculature of jejunal control segments and all colon segments was similar to described normal microvasculature of the equine jejunum and ascending colon. In jejunal iso segments, intramural perfusion was redistributed away from the mucosa. In the villi, the central arteriole was short and convoluted and the subepithelial capillaries were not filled. The submucosal vessels and crypt capillaries were congested, compared with those of controls, and the serosal vessels were not filled in the ischemic segments. Histologic grade II-III mucosal lesion was seen in jejunal iso segments. Reperfused jejunal segments had a transmural hyperemic response, and previously unfilled capillaries were observed in all intestinal layers. After reperfusion, the mucosal lesion progressed to grade III-IV and a cellular infiltrate and edema formation were observed in the serosa.

The intramural vasculature of the ischemic and reperfused colon remain unchanged. Minimal histologic damage was observed in the colon after 70 minutes of iso or after 60 minutes of reperfusion.

Free access
in American Journal of Veterinary Research