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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
in Journal of the American Veterinary Medical Association

Summary

The signalment, clinical and laboratory findings of surgical conditions, treatment, and outcome of 102 cases of descending colon disease in horses were reviewed. Abnormal conditions were categorized as enteroliths, impactions, strangulating lipomas, fecaliths, foreign body obstruction, volvulus, nephrosplenic entrapment, and other conditions. Eleven breed categories of horses were seen during this period. Arabians, ponies, and American miniature horses were more predisposed to descending colon disease than other breeds (P < 0.05). Female horses and animals >15 years old were more likely to be affected with descending colon disease, whereas horses <5 years old were less likely to be affected (P < 0.05). More specifically, Arabians, Quarter Horses, and Thoroughbreds >10 years old were breeds that were overrepresented when compared with the hospital population (P < 0.05). Enteroliths were most commonly seen in horses between 5 and 10 years old (P < 0.05) and were not seen in horses <2 years old. Enteroliths had a tendency to develop more commonly in Arabians and in female horses. Impactions affected horses >15 years old (P < 0.05) and had a greater tendency to affect ponies and American miniature horses. Female horses were more commonly affected by impaction than were males. Strangulating lipomas were commonly seen in horses >15 years old (P < 0.05) and more specifically female Quarter Horses (P < 0.05). Fecaliths tended to be a disease of horses <1 year old or >15years old and affected males more commonly than females. Ponies, American miniature horses, mixed-breed horses, and mustangs were the breeds most commonly affected. Surgical conditions were categorized as vascular (16%) or nonvascular (84%) conditions. Vascular conditions included strangulating lipomas (6%) and other conditions (10%). Nonvascular conditions included enteroliths (40%), impactions (25%), fecaliths (13%), and other conditions (6%). Horses with vascular lesions were older than horses with nonvascular conditions (P < 0.05). Peritoneal fluid values were high for all surgical conditions of the descending colon. Nucleated cell count and total protein concentration in peritoneal fluid retrieved from horses with vascular lesions were higher than in horses with nonvascular lesions (P < 0.01). Palpation per rectum revealed abnormal findings more commonly in horses with vascular compromise (P < 0.05). Of those horses taken to surgery, 91% were recovered from anesthesia and discharged; 90% of horses, for which the condition was monitored to at least 6 months after surgery, were alive. All horses that were medically treated were alive at least 6 months after discharge.

Free access
in Journal of the American Veterinary Medical Association

Summary

To quantify some components of prepurchase evaluations in horses, records from 134 evaluations performed during a 2-year period were reviewed and the outcome was determined via telephone follow-up interview. Sixty-two percent of the prepurchase evaluations had been performed at the clinic and 38% had been performed in the field by the ambulatory service. All evaluations included physical and lameness examinations, whereas radiography (49%), endoscopy (15%), nerve blocking (5%), transrectal palpation (3%), hematologic analysis (2%), electrocardiography (2%), drug testing for analgesic agents (2%), and ultrasonography of the flexor tendons (1%) were not always performed. Fifty-nine percent of horses evaluated at the clinic were radiographed, compared with 33% of horses evaluated in the field (P < 0.05).

Thirty-seven percent of horses evaluated were judged serviceable for their intended use. Thirty-five percent of horses evaluated at the clinic were assessed to be serviceable, compared with 41% of those evaluated in the field (P < 0.05). Horses used for pleasure riding (48%) tended to be considered serviceable more often than horses used for more athletic endeavors (3-day eventing, 33%; hunter/jumper, 24%; show, 31%; dressage, 30%). The most common basis for finding a horse unserviceable was lameness (88%).

On the basis of a telephone interview, horses were divided into 5 groups: horses determined unserviceable on evaluation and not purchased (n = 40); horses determined unserviceable on evaluation, purchased, and then found serviceable on follow-up interview (n = 35); horses determined unserviceable on evaluation, purchased, and then found unserviceable on follow-up interview (n = 9); horses determined serviceable on evaluation, purchased, and found serviceable on follow-up interview (n = 42); and horses determined serviceable on evaluation, purchased, and found unserviceable on follow-up interview (n = 8).

The buyer and seller were present at the evaluation in 34% of cases. The buyer alone was present in 57% of cases, the seller alone in 4% of cases, whereas neither was present in 6% of cases. The potential buyer had used the horse for its intended purpose prior to the prepurchase evaluation in 39% of cases for a mean time of 20.5 days, but this did not appear to affect the serviceability of the horse on follow-up evaluation. Five horses that were leased for > 6 months prior to purchase were all serviceable on follow-up interview, irrespective of the findings at the time of the prepurchase evaluation.

There was a tendency for the value of horses examined at the clinic to be higher than those evaluated by the ambulatory service. The price paid by the buyer was reduced through negotiations on the basis of the prepurchase evaluation in 6% of cases.

Lameness was seen only in horses within the unserviceable group. Lameness tended to be seen more often in horses valued > $2,500 (61%, 46/75) than in horses valued ≤ $2,500 (48%, 28/59). Lameness was associated with 92% (22/24) of horses valued at > $2,500 within the group judged to be unserviceable and not purchased.

Radiography was performed to investigate a specific lameness in 24% (32/134) of evaluations and for survey purposes in 25% (34/134) of evaluations. Of horses radiographed within the unserviceable group, radiography commonly was performed for specific lameness (84%, 32/38) and rarely for survey purposes (24%, 9/38), whereas only survey radiographs were obtained from the serviceable group because no horses exhibited a specific lameness. Radiography was significantly (P < 0.05) more likely to have been performed in horses valued > $2,500 (65%, 49/75) than in those valued < $2,500 (29%, 17/59), and this trend was reflected in all categories. For survey radiographs, the combination of tarsi and bilateral distal forelimbs was the most commonly radiographed area (44%). Bilateral distal forelimbs alone were the second most commonly radiographed area (41%).

A written report summarizing the findings of the evaluation was furnished in 24% of cases. At the time of follow-up interview, 75% of buyers indicated that they would have liked a written report.

Free access
in Journal of the American Veterinary Medical Association