A novel ultrasonographic assisted technique for desmotomy of the palmar/plantar annular ligament in horses.

OBJECTIVES: To describe an ultrasound assisted technique for desmotomy of the palmar/plantar annular ligament (PAL), determine its efficacy and intraoperative complications. STUDY DESIGN: Cadaveric and in vivo study. ANIMALS: Cadaveric limbs (n = 12), adult horses (n = 4), and clinical cases (n = 2). METHODS: Ultrasound assisted desmotomy of the palmar/plantar annular ligament (UAD-PAL) was performed in cadaveric limbs and in standing horses with the operated limb placed in a distal limb splint. The procedure was performed under general anesthesia and was followed by tenoscopic examination in 2 clinical cases. A hook knife was developed for the procedure. Complete transection was assessed by postmortem dissection (10 forelimbs, 10 hindlimbs) and tenoscopic examination (1 forelimb, 1 hindlimb). Thickness of PAL, surgery time, other intraoperative parameters and complications associated with the procedure were recorded. RESULTS: Complete PAL transection was accomplished in 20/22 limbs. No iatrogenic damage to adjacent intrathecal structures was identified in any case. The instrument was correctly positioned on the first attempt in 19/22 cases. The most common intraoperative complication was inadvertent subcutaneous placement of the instrument (n = 2). Significant thickening of the PAL (3 mm) was present in 1/2 limbs in which complete transection was not achieved. CONCLUSIONS: UAD-PAL with the custom-made hook knife was effective at transecting the PAL with minimal intraoperative complications. The procedure can be performed in standing sedated horses. Another method should be considered in horses with thickened PAL.

Pharmacokinetics of a combination of amikacin sulfate and penicillin G sodium for intravenous regional limb perfusion in adult horses.

The aim of this study was to determine the pharmacokinetics of amikacin and penicillin G sodium when administered in combination as an intravenous regional limb perfusion (IVRLP) to horses. Seven healthy adult horses underwent an IVRLP in the cephalic vein with 2 g of amikacin sulfate and 10 mill IU of penicillin G sodium diluted to 60 mL in 0.9% saline. A pneumatic tourniquet set at 450 mmHg was left in place for 30 min. Synovial fluid was collected from the metacarpophalangeal joint 35 min and 2, 6, 12, and 24 h after infusion of the antimicrobials. Concentrations of amikacin and penicillin in synovial fluid were quantitated by liquid chromatography tandem-mass spectrometry analysis. Therapeutic concentrations of amikacin and penicillin for equine-susceptible pathogens were achieved in the synovial fluid. Maximum synovial concentrations (Cmax) (mean ± SE) for amikacin and penicillin were 132 ± 33 µg/mL and 8474 ± 5710 ng/mL, respectively. Only 3 horses had detectable levels of penicillin at 6 h and 1 at the 12 h sample. The combination of amikacin with penicillin G sodium via IVDLP resulted in reported therapeutic concentrations of both antibiotics in the synovial fluid. The Cmax:MIC (minimum inhibitory concentration) ratio for amikacin was 8:1 and Time > MIC for penicillin was 6 h. At 24 h, the mean concentration of amikacin was still above 4 µg/mL. Terminal elimination rate constants (T1/2 lambdaz) were 13.6 h and 2.8 h for amikacin and penicillin, respectively. The use of IVDLP with penicillin may therefore not be practical as rapid clearance of penicillin from the synovial fluid requires frequent perfusions to maintain acceptable therapeutic concentrations.

L'objectif de la présente étude était de déterminer la pharmacocinétique de l'amikacine et de la pénicilline G sodique lorsqu'administrées en combinaison par perfusion intraveineuse régionale d'un membre (PIVRM) à des chevaux. Sept chevaux adultes ont reçu une PIVRM dans la veine céphalique avec 2 g de sulfate d'amikacine et 10 millions d'UI de pénicilline G sodique dilués dans 60 mL de saline 0,9 %. Un tourniquet pneumatique réglé à 450 mmHg a été laissé en place pour 30 min. Du liquide synovial a été récolté de l'articulation métacarpo-phalangienne 35 min, 2, 6, 12, et 24 h après l'infusion des antimicrobiens. Les concentrations d'amikacine et de pénicilline dans le liquide synovial furent mesurées par spectrométrie de masse en tandem avec la chromatographie en phase liquide. Les concentrations thérapeutiques d'amikacine et de pénicilline pour des agents pathogènes équins sensibles ont été atteintes dans le liquide synovial. Les concentrations synoviales maximales (Cmax) [moyenne ± écart-type (EC)] pour l'amikacine et la pénicilline étaient de 132 ± 33 µg/mL et 8474 ± 5710 ng/mL, respectivement. Seulement 3 chevaux avaient des quantités détectables de pénicilline à 6 h et un seul pour l'échantillon de 12 h. La combinaison d'amikacine et de pénicilline G sodique via PIVRM a permis de rapporter des concentrations thérapeutiques des deux antibiotiques dans le liquide synovial. Le ratio Cmax-CMI (concentration minimale inhibitrice) pour l'amikacine était de 8:1 et la période de Temps > CMI pour la pénicilline était de 6 h. À 24 h, la concentration moyenne d'amikacine était toujours supérieure à 4 µg/mL. Les constantes du taux d'élimination terminal (T1/2 lambdaz) étaient 13,6 h et 2,8 h pour l'amikacine et la pénicilline, respectivement. L'utilisation de PIVRM avec la pénicilline ne serait ainsi pas pratique étant donné que la clairance rapide de la pénicilline à partir du liquide synovial requière des perfusions fréquentes pour maintenir des concentrations thérapeutiques acceptables.(Traduit par Docteur Serge Messier).

A preliminary study of silver sodium zirconium phosphate polyurethane foam wound dressing on wounds of the distal aspect of the forelimb in horses.

OBJECTIVE: To determine if application of silver sodium zirconium phosphate polyurethane semi-occlusive foam (SPF) dressing would improve measures of wound healing and decrease bacterial contamination compared with a non-adherent, absorbent dressing applied to wounds created on the distal aspect of the equine limb. STUDY DESIGN: Controlled randomized experimental study. ANIMALS: Adult Quarter Horse and Thoroughbred horses (n = 5). METHODS: One 6.25 cm(2) wound was created on the dorsomedial aspect of the proximal metacarpus on each forelimb. A SPF dressing was applied to 1 randomly assigned limb as a treatment and a non-adherent, absorbent dressing was applied to the opposite limb as control. Bandages were changed every 3 days for 60 days. Granulation tissue was scored every 3 days, wound area measured every 6 days, and wound bed was cultured every 12 days. RESULTS: SPF-treatment wounds had significantly decreased wound area and decreased granulation tissue scores when evaluated <30 days and over the 60 day study, although complete wound healing times were not significantly different. Bacteria were cultured from all wounds at varying times throughout the study. CONCLUSIONS: The SPF wound dressing improved some measures of wound healing compared with the control dressing, most significantly during the first 30 days. This suggests that the SPF wound dressing may be useful in the early management of wounds on the equine lower limb. Further studies using the SPF dressing are needed to characterize the temporal and cellular effects on wound healing and evaluate this dressing in a clinical environment.

Evaluation of 3 handheld portable analyzers for measurement of L-lactate concentrations in blood and peritoneal fluid of horses with colic.

OBJECTIVE: To compare 3 portable handheld analyzers with a bench top blood gas analyzer for measurement of blood and peritoneal fluid L-lactate concentrations in horses admitted with signs of colic. STUDY DESIGN: Prospective clinical study. SAMPLE POPULATION: Blood and peritoneal fluid from horses with colic. METHODS: L-lactate concentrations in heparinized blood and peritoneal fluid were measured serially on 10 occasions to evaluate repeatability of the portable analyzers. Blood and peritoneal fluid L-lactate concentrations were simultaneously evaluated by a bench top and 3 portable analyzers and the results compared by intraclass correlation coefficients and Bland Altman plots. L-Lactate concentrations in a subgroup of peritoneal fluid samples were evaluated by a chromogenic laboratory assay and compared with the bench top and the handheld analyzers. RESULTS: Portable lactate analyzers had good intra-analyzer reliability for peritoneal fluid. Two portable analyzers had poor intra-analyzer reliability for mid concentrations of L-lactate in blood. L-lactate measurements from portable analyzers were closer to the bench top analyzer at low concentrations of L-lactate than at higher concentrations. Compared with the bench top analyzer, the Lactate Pro and Lactate Plus have the highest intraclass correlation coefficient and the smallest bias for peritoneal fluid and blood L-lactate, respectively. The bench top analyzer and the Lactate Pro had the highest level of agreement for peritoneal fluid compared with the chromogenic assay. CONCLUSIONS: Although portable analyzers are alternatives for the measurement of L-lactate concentration in field situations, clinicians need to be aware of the variable results between analyzers, especially when extrapolating means or cutoff values from studies using different lactate analyzers.

In vivo and in vitro evaluation of the effects of domperidone on the gastrointestinal tract of healthy horses.

OBJECTIVE: To determine the effects of domperidone on in vivo and in vitro measures of gastrointestinal tract motility and contractility in healthy horses. SAMPLE: 18 adult horses and tissue samples from an additional 26 adult horses. PROCEDURES: Domperidone or placebo paste was administered to healthy horses in a 2-period crossover study. Gastric emptying was evaluated after oral administration of domperidone paste (1.1 or 5.0 mg/kg) or placebo paste by means of the acetaminophen absorption test in 12 horses. Frequency of defecation, weight of feces produced, fecal moisture, and stomach-to-anus transit time of microspheres were evaluated after administration of domperidone paste (1.1 mg/kg) or placebo paste in 6 horses. The effect of domperidone on smooth muscle contractile activity in samples of duodenum, jejunum, ileum, or colon obtained from 26 horses immediately after euthanasia (for nonsystemic medical problems) was investigated. RESULTS: Oral administration of 5.0 mg of domperidone/kg increased peak plasma acetaminophen concentration and area under the curve, indicating increased gastric emptying. Administration of 1.1 mg of domperidone/kg had no effect on gastric emptying, transit time, defecation frequency, or amount and moisture of excreted feces. Contractile activities of circular and longitudinal muscle strips from the duodenum, jejunum, ileum, or colon were not altered by domperidone. Dopamine increased contractile activity of longitudinal muscle strips but not that of circular muscle strips from the midjejunum. Domperidone decreased the dopamine-induced contractile activity of midjejunal longitudinal muscle strips. CONCLUSIONS AND CLINICAL RELEVANCE: The potential beneficial effects of domperidone in horses with ileus need to be evaluated in horses with decreased gastric emptying or adynamic ileus.

Pharmacokinetics, pharmacodynamics, and safety of zoledronic acid in horses.

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.

In vivo and in vitro effects of neostigmine on gastrointestinal tract motility of horses.

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.

Use of zoledronate for treatment of a bone fragility disorder in horses.

OBJECTIVE: To assess clinical outcomes and scintigraphic findings in horses with a bone fragility disorder (BFD) treated with zoledronate (a nitrogen-containing bisphosphonate). DESIGN: Prospective uncontrolled clinical trial. ANIMALS: 10 horses with evidence of a BFD. PROCEDURES: Signalment, history, and geographic location of horses' home environments were recorded. Physical examinations, lameness evaluations, and nuclear scintigraphy were performed. Diagnosis of a BFD was made on the basis of results of clinical and scintigraphic examination. Each horse was treated with zoledronate (0.075 mg/kg [0.034 mg/lb, IV, once]) at the time of diagnosis. Horses were reevaluated 6 months after treatment. RESULTS: Affected horses were from the central and coastal regions of California and had ≥ 1 clinical sign of the disorder; these included scapular deformation (n = 2), lordosis (1), nonspecific signs of musculoskeletal pain (1), and lameness that could not be localized to a specific anatomic region (9). All horses had multiple sites of increased radiopharmaceutica uptake during initial scintigraphic evaluation of the axial skeleton and bones of 1 or both forelimbs. Six months after treatment, clinical improvement (defined as improvement in the lameness score, resolution of signs of musculoskeletal pain, or both) was detected in 9 of 10 horses; scintigraphic uptake was unchanged (n = 2) or subjectively decreased (8). No adverse effects attributed to zoledronate treatment were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with zoledronate appeared to be useful in improving clinical outcome and scintigraphic findings in horses with a BFD; however, future placebo-controlled studies are necessary to accurately determine efficacy and long-term safety.

Effects of phenylbutazone on gene expression of cyclooxygenase-1 and -2 in the oral, glandular gastric, and bladder mucosae of healthy horses.

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, p.o., 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.

Peritoneal and plasma D-lactate concentrations in horses with colic.

OBJECTIVE: To evaluate the association between peritoneal fluid and plasma d-lactate concentration with variables used in the diagnosis and prognosis of horses with colic. ANIMALS: Clinically healthy horses (n=6) and 90 horses with colic. STUDY DESIGN: Prospective cross-sectional study. METHODS: D-lactate concentration was determined in peritoneal fluid and plasma of all horses. Information on other blood and peritoneal fluid variables, signalment, results from the physical examination, outcome, need for surgery, lesion location, and type was retrieved from medical records. RESULTS: Peritoneal D-lactate concentration was strongly correlated with plasma D-lactate concentration (r=0.71; P<.001). Peritoneal and plasma D-lactate concentrations were positively correlated with peritoneal (r=0.8; P<.001) and plasma L-lactate (r=0.33; P=.001) concentrations, respectively. Peritoneal D-lactate concentration was negatively correlated with survival to discharge (U=430.5; P<.001). Median peritoneal D-lactate concentration of horses with septic peritonitis (455.2 µmol/L) and horses with gastrointestinal rupture (599.5 µmol/L) were higher compared with horses with nonstrangulating obstructions (77.7 µmol/L). A cut-off concentration of peritoneal D-lactate of 116.6 µmol/L had a sensitivity of 0.813 and a specificity of 0.651 to differentiate between nonstrangulating and strangulating obstructions. CONCLUSIONS: Peritoneal D-lactate concentration may be more useful for identifying horses with strangulating obstructions (high sensitivity, low probability of a false negative) than to ruling out strangulating obstruction (moderate specificity, high probability of a false positive).

Expression of cyclooxygenase genes in the jejunum of horses during low-flow ischemia and reperfusion.

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 ß-actin and hypoxanthine phosphoribosyltransferase, whereas glyceraldehyde 3-phosphate dehydrogenase and ß-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.

Effect of gastric ulceration on physiologic responses to exercise in horses.

OBJECTIVE: To develop a protocol to induce and maintain gastric ulceration in horses and to determine whether gastric ulceration affects physiologic indices of performance during high-speed treadmill exercise. ANIMALS: 20 healthy Thoroughbreds. PROCEDURES: Each horse was acclimatized to treadmill exercise during a 2-week period. Subsequently, baseline data were collected (day 0) and each horse began an incrementally increasing exercise training program (days 1 through 56). Beginning on day 14, horses were administered omeprazole (4 mg/kg, PO, q 24 h until day 56) or no drug (10 horses/group) and underwent alternating 24-hour periods of feeding and feed withholding for 10 days to induce gastric ulceration. Extent of gastric ulceration was assessed weekly thereafter via gastroscopy. Physiologic indices of performance were measured at days 0 and 56. Gastric ulceration and exercise performance indices were compared within and between groups. RESULTS: In untreated horses, gastric ulcers were induced and maintained through day 56. Gastric ulcer formation was prevented in omeprazole-treated horses. There were significant interactions between time (pre- and post-training data) and treatment (nonulcer and ulcer groups) for mass-specific maximal O(2) consumption ([Formula: see text]O(2max)/M(b)) and mass-specific maximal CO(2) production ([Formula: see text]CO(2max)/M(b)). Post hoc analysis revealed a difference between groups for [Formula: see text]O(2max)/M(b) at day 56. Within-group differences for [Formula: see text]O(2max)/M(b) and [Formula: see text]CO(2max)/M(b) were detected for omeprazole-treated horses, but not for the horses with ulcers. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, gastric ulcers were induced and maintained by use of alternating periods of feeding and feed withholding in association with treadmill exercise (simulated racetrack training). Gastric ulcers adversely affected physiologic indices of performance in horses.

Influence of diet and water supply on mineral content and pH within the large intestine of horses with enterolithiasis.

To determine the effects of two diets and water supplies on intestinal pH and mineral concentrations in the colon of horses, and to identify whether differences in these parameters exist in horses with and without enterolithiasis, surgical fistulation of the right dorsal colon was performed in six adult horses, three with and three without enterolithiasis. Each horse underwent four feeding trials: grass hay and untreated water, alfalfa hay and untreated water, grass hay with filtered/softened water, and alfalfa hay with filtered/softened water. Samples of colonic contents were analyzed for pH, dry matter, and mineral concentrations. Horses with enterolithiasis had higher calcium, magnesium, phosphorus and sulfur concentrations and higher pH in colonic contents than controls. Horses fed alfalfa had lower colonic sodium and potassium, higher calcium, magnesium, phosphorus and sulfur concentrations, and a more alkaline pH than those fed grass. Grass hay consumption leads to reduced concentrations of select minerals and a more acidic colonic environment compared with alfalfa, probably beneficial in the prevention of enterolithiasis. Under controlled dietary and management conditions, horses with enterolithiasis have differences in colonic mineral and pH parameters that may be consistent with physiological differences between horses with and without the disease.

Prevalence of gastric ulcers in Thoroughbred broodmares in pasture: a preliminary report.

Gastroscopic examinations were performed in 62 Thoroughbred broodmares (33 pregnant, 29 non-pregnant) at one breeding farm to investigate the prevalence of gastric ulceration. Age, pregnancy status, race earnings, last race start, herd size, medical history, number of live foals, breeding years, feed type and number of feedings were recorded, plus coat condition and body condition score were determined. Twenty-one mares were re-evaluated after foaling, and the foaling date, foal weight at birth and placenta weight were recorded. The overall prevalence of gastric ulcers was 70.9%, with a median ulcer score of 3.0 (range: 2-5). Most ulcers were present on the squamous portion of the stomach, while two mares had glandular ulcers. There were no differences in the presence, location and severity of gastric ulcers between pregnant and non-pregnant mares. Furthermore, there were no significant associations between the variables measured and the presence of gastric ulceration. The prevalence of gastric ulceration in this specific population of horses was higher than expected and further investigation is warranted to determine the factors that contributed to this finding.

Evaluation of the effect of ranitidine on gastroduodenal contractile activity and gastric emptying in horses.

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.

Evaluation of continuous infusion of lidocaine on gastrointestinal tract function in normal horses.

OBJECTIVE: To determine the effect of continuous infusion of lidocaine on fecal transit time in normal horses. STUDY DESIGN: Experimental randomized cross-over study. ANIMALS: Healthy horses (n=6). METHODS: Barium-filled microspheres were administered to horses by nasogastric intubation and feces were collected every 2 hours for 4 days. A bolus of 2% lidocaine (1.3 mg/kg) was administered randomly, followed by a continuous infusion of lidocaine (0.05 mg/kg/min) for 3 days or an equivalent volume of saline. The washout period was 10 days. Variables assessed included defecation frequency, weight of feces produced, intestinal transit time (number of microspheres observed on radiographs), fecal moisture content, borborygmus score, heart and respiratory rate, and signs of lidocaine toxicity (e.g., ataxia, CNS depression). RESULTS: During the first 24 hours of lidocaine administration, mean (+/-SD) fecal output (10.8+/-6.9 kg) was decreased compared with controls (15+/-4.9 kg). Mean (+/-SEM) time for passing 50% of the barium-filled microspheres was shorter in controls (42+/-1.13 hours) compared with the lidocaine group (50+/-1.32 hours). CONCLUSIONS: Continuous infusion of lidocaine increases the transit time of feces in normal horses. CLINICAL RELEVANCE: Clinicians need to be aware of the effects of using a continuous infusion of lidocaine on the transit time of feces in normal horses, with a potential for exacerbating those effects when combined with drugs that decrease motility and in horses with medical colic (e.g., impaction) or where a diagnosis has not been made.

Long-term outcome associated with intratumoral chemotherapy with cisplatin for cutaneous tumors in equidae: 573 cases (1995-2004).

OBJECTIVE: To determine outcome associated with cutaneous tumors treated via intratumoral chemotherapy with cisplatin and identify risk factors affecting local tumor control and complications in equidae. DESIGN: Retrospective case series. ANIMALS: 573 equidae with 630 cutaneous tumors. PROCEDURES: Medical records of horses, mules, donkeys, and ponies with cutaneous tumors treated via intratumoral chemotherapy with cisplatin were analyzed. RESULTS: 549 horses, 13 mules, 8 donkeys, and 3 ponies with 630 histologically confirmed cutaneous tumors were included. Tumors included sarcoids (n = 409), squamous cell carcinomas (151), soft tissue sarcomas (28), cutaneous lymphomas (26), and melanomas (16). Overall cure rate, defined as local control at 4 years, was 93.3%. For all tumor stages combined, cure rates after 1 course of treatment were 96.3% for sarcoids, 96% for lymphomas, 88% for squamous cell carcinomas, 85% for soft tissue sarcomas, and 81% for melanomas. Treatment protocol, tumor stage, and prior treatment were significant prognostic factors for tumor control. Treatment efficacy was lower for large tumors, those with gross postoperative residual disease, and those that had been treated previously with other modalities. Treatment was well tolerated. Local reactions were more likely to occur and to be more severe after the third and fourth treatment sessions. CONCLUSIONS AND CLINICAL RELEVANCE: Results confirmed the value of intratumoral chemotherapy with cisplatin for treatment of cutaneous tumors in equidae. The results cannot be extrapolated to other formulations of cisplatin or other protocols that might be used.

Pharmacokinetics and in vitro effects of tegaserod, a serotonin 5-hydroxytryptamine 4 (5-HT4) receptor agonist with prokinetic activity in horses.

Tegaserod, a serotonin agonist, has been shown to have prokinetic effects in horses, but pharmacokinetic information is not currently available. The pharmacokinetics and in vitro effects of tegaserod were evaluated. Tegaserod increased the contractile activity of smooth muscle preparations of the equine pelvic flexure. Pertinent pharmacokinetic parameters for a single IV and oral dose were determined. Therapeutic plasma concentrations of tegaserod were achieved by a single oral dose at 0.27 mg/kg. These findings indicate that further clinical studies are warranted to investigate potential benefits in cases of functional gastrointestinal motility disorders in horses.

Effect of intrathecal amikacin administration and repeated centesis on digital flexor tendon sheath synovial fluid in horses.

OBJECTIVE: To determine the effect of intrathecal amikacin administration and repeated tenovaginocentesis on the total nucleated cell count (TNCC), total protein (TP) concentration and cytologic characteristics of synovial fluid of the equine digital flexor tendon sheath (DFTS). STUDY DESIGN: Randomized, cross-over experimental design. ANIMALS: Adult horses (n=8). METHODS: Synovial fluid was aseptically collected from the DFTS and either 1 mL amikacin sulfate (250 mg/mL) or lactated Ringer's solution (LRS) was injected into the DFTS. Serial synovial fluid samples were obtained at 0, 12, 24, 48, and 72 hours. The opposite treatment was administered to the contralateral DFTS after a washout period of 2 weeks. RESULTS: Treatment increased TP concentration, TNCC, percentage of neutrophils, and neutrophil counts from baseline levels. There was no difference between treatment of the DFTS with amikacin or LRS. Values peaked at 12-24 hours after the initial centesis and then declined toward baseline levels. CONCLUSIONS: Injection and repeat centesis of the normal DFTS with 250 mg amikacin or an equivalent volume of LRS resulted in mild increases in synovial fluid analytes from baseline. Synovial inflammation in this study was not accompanied by lameness at the walk and measured analytes returned toward baseline levels within 12-24 hours of first injection. CLINICAL RELEVANCE: The effect of tenovaginocentesis and intrathecal administration of amikacin or LRS on DFTS synovial fluid values are modest in most horses; however, some horses can develop marked increases in synovial fluid values that may be interpreted as sepsis.

Comparison of one-layer (continuous Lembert) versus two-layer (simple continuous/Cushing) hand-sewn end-to-end anastomosis in equine jejunum.

OBJECTIVE: To evaluate single and double layer end-to-end anastomosis in equine jejunum. STUDY DESIGN: Experimental in vitro study. ANIMALS: Mid-jejunal sections from 12 adult horses without gastrointestinal disease. METHODS: Jejunal end-to-end anastomoses were performed by a continuous Lembert pattern or a simple continuous pattern oversewn with a Cushing pattern. Jejunal segments were distended with fluid at 1 L/min, and intraluminal pressure at failure, and mode of failure were recorded. Bursting pressure and bursting wall tension were calculated. Anastomosis construction time and degree of luminal reduction were recorded. Results- Single layer anastomoses were constructed in less time than 2-layer anastomoses. Both anastomotic techniques resulted in luminal reduction compared with control tissue; however, the reduction was smaller with a 1-layer continuous Lembert anastomosis. No differences were noted in bursting pressure or bursting wall tension between groups. CONCLUSIONS: Anastomosis using a 1-layer continuous Lembert pattern resulted in a larger stoma, was faster to perform, and as strong as a 2-layer anastomosis. CLINICAL RELEVANCE: Use of a 1-layer continuous Lembert pattern for jejunojejunosotomy may be beneficial by decreasing anastomosis time and produce a larger stoma than a 2-layer anastomosis.