Objective—To assess pharmacokinetics of pregabalin in horses after a single intragastric or IV dose.
Animals—5 healthy adult mares.
Procedures—Horses received 1 dose of pregabalin (approx 4 mg/kg) via nasogastric tube in a crossover-design study; after a 3-week washout period, the same dose was administered IV. Food was not withheld. Plasma pregabalin concentrations in samples obtained 0 to 36 hours after administration were measured by use of ultra-performance liquid chromatography with triple quadrupole tandem mass spectrometry. Pharmacokinetic variables were estimated by means of noncompartmental analysis.
Results—Mild sedation was observed in 2 horses following intragastric and IV pregabalin administration. Signs of mild, transient colic or behavioral abnormalities were observed in all horses following IV administration. After intragastric administration, median (range) maximal plasma concentration was 5.0 μg/mL (4.4 to 6.7 μg/mL), time to maximal plasma concentration was 1. 0 hour (0.5 to 2.0 hours), elimination half-life was 8.0 hours (6.2 to 9.4 hours), and area under the curve from time 0 to infinity (AUC0–∞) was 47.2 μg·h/mL (36.4 to 58.4 μg·h/mL). After IV administration, initial concentration was 22.2 μg/mL (19.8 to 27.7 μg/mL), elimination half-life was 7.74 hours (6.94 to 8.17 hours), and AUC0–∞ was 48.3 μg·h/mL (44.8 to 57.2 μg·h/mL). Bioavailability was 97.7% (80.7% to 109.8%). Median predicted values for minimal, mean, and maximal steady-state plasma concentrations after intragastric administration assuming an 8-hour dosing interval were 3.9, 5.3, and 6.3 μg/mL, respectively.
Conclusions and Clinical Relevance—At a simulated intragastric dosage of approximately 4 mg/kg every 8 hours, median pregabalin steady-state plasma concentration in healthy horses was within the therapeutic range reported for humans. Therapeutic concentrations and safety of this dosage have not been established in horses.
Case Description—A 2-year-old alpaca was evaluated because of acute onset of cervical scoliosis.
Clinical Findings—Physical examination revealed severe scoliosis of the caudal portion of the cervical vertebral column with a C-shaped curvature to the right side. No gait deficits were observed. Cervical radiography confirmed severe curvature of C4 to C6 but did not reveal any bony changes. Cerebrospinal fluid had high total protein concentration and extremely high nucleated cell count with a high proportion of eosinophils, suggesting parasitic infection.
Treatment and Outcome—The alpaca was treated for suspected parelaphostrongylosis with ivermectin, fenbendazole, flunixin, vitamin E, thiamine, physical therapy, and a custom-made neck brace. The alpaca's condition continued to deteriorate, and it developed tetraparesis and ataxia and was euthanized after approximately 1 month. Microscopic evaluation of the cervical spinal cord revealed marked vacuolar changes in the left medial portion of the ventral funiculus, mild lymphoplasmacytic infiltration, and multifocal granulomas. The lesions were continuous from C1 to C7 and were compatible with parasite migration.
Clinical Relevance—To the authors' knowledge, this is the first report of acquired scoliosis in an alpaca, which appears to represent an unusual manifestation of parelaphostrongylosis that was reported in horses.
Objective—To estimate the prevalence of fecal shedding of Salmonella spp among bovine patients at a veterinary teaching hospital, to identify risk factors for fecal shedding of Salmonella organisms, and to characterize the serotypes.
Design—Retrospective cohort study.
Sample Population—5,398 hospitalized cattle.
Procedures—Data were collected for all cattle admitted during an 11-year period. Fecal shedding of Salmonella spp was determined by means of standard bacteriologic culture. Multivariable logistic regression models were used to identify risk factors for shedding of Salmonella spp among patients.
Results—The prevalence of Salmonella shedding among clinical suspects was 6.5% (50/768), whereas that among nonsuspects tested through routine surveillance was 2.5% (50/2,020). Among clinical suspect calves, fecal shedding of Salmonella spp was more likely for those admitted in the fall (odds ratio [OR], 5.9), those with septicemia (OR, 3.3), or those with an umbilical hernia (OR, 8.6). Among clinical suspect adult cattle, those with enteritis (OR, 9.9) or metritis (OR, 5.2) were more likely to be shedding Salmonella spp. Among nonsuspect cattle, none of the variables were significant predictors of shedding status. Twenty-one serotypes were detected during the study period, with the most common being Salmonella enterica serotypes Typhimurium (33%), Newport (23%), and Agona (12%).
Conclusions and Clinical Relevance—Seasonal and disease risk factors for fecal shedding of Salmonella spp were evident among clinical suspect cattle admitted to a veterinary teaching hospital. In contrast, lack of significant associations among nonsuspect cattle would suggest that targeted screening within this population is not warranted.
Objective—To evaluate clinical variables assessed during the first 24 hours of hospitalization as prognostic indicators for nonambulatory cattle treated by use of a flotation tank.
Design—Retrospective case series.
Animals—51 nonambulatory cattle that underwent flotation treatment.
Procedures—Signalment, history, serum biochemical analyses, patient behavior during flotation, and outcome data were collected from medical records. Outcome was survival to discharge from the hospital or nonsurvival (death or euthanasia). Data were analyzed by use of Wilcoxon rank sum, Fisher exact, and χ2 tests.
Results—19 of 51 cattle survived. Survivors and nonsurvivors did not differ significantly with regard to median weight; age; stage of lactation; duration of recumbency prior to flotation; serum potassium, ionized calcium, or phosphate concentrations at admission to the hospital; or serum creatine kinase activity (value at admission to the hospital, highest value, and last recorded value). Cattle that were able to walk out of the tank after the first flotation treatment were 4.8 times as likely to survive as those that could not. Cattle that did not eat during flotation treatment were 1.9 times as likely to die as those that ate. Cattle that stood apparently normally on all limbs during the first flotation treatment were 2.9 times as likely to survive as those that had an asymmetric stance or were unable to stand.
Conclusions and Clinical Relevance—Results indicated that objective variables evaluated during the first 24 hours of hospitalization and flotation treatment are associated with outcome among nonambulatory cattle; findings might assist in logical decision making with respect to treatment options.
Objective—To determine whether equine motor neuron disease (EMND) could be induced in adult horses fed a diet low in vitamin E and high in copper and iron.
Animals—59 healthy adult horses.
Procedure—Horses in the experimental group (n = 8) were confined to a dirt lot and fed a concentrate low in vitamin E and high in iron and copper in addition to free-choice grass hay that had been stored for 1 year. Control horses (n = 51) were fed a concentrate containing National Research Council–recommended amounts of copper, iron, and vitamin E. The hay fed to control horses was the same as that fed to experimental horses, but it had not been subjected to prolonged storage. Control horses had seasonal access to pasture, whereas experimental horses had no access to pasture. Horses that developed clinical signs of EMND were euthanatized along with an age-matched control horse to determine differences in hepatic concentrations of vitamin E, vitamin A, copper, iron, and selenium.
Results—4 experimental horses developed clinical signs of EMND. Plasma concentrations of vitamin E decreased in all 8 experimental horses. There were no significant changes in plasma concentrations of vitamin A, selenium, and copper or serum concentrations of ferritin. There were no significant differences in those analytes between experimental horses with EMND and experimental horses that did not develop EMND. No control horses developed EMND.
Conclusions and Clinical Relevance—Results suggest that lack of access to pasture, dietary deficiency of vitamin E, or excessive dietary copper are likely risk factors for EMND.
OBJECTIVE To determine effects of oral administration of Yunnan Baiyao on platelet activation, coagulation, and fibrinolysis in healthy horses.
ANIMALS 12 healthy adult horses.
PROCEDURES In a randomized blinded crossover study that included a 4-week washout period between treatments, horses were orally administered a paste containing Yunnan Baiyao (15 mg/kg) or placebo at 12-hour intervals for 3 days. Blood samples were collected before start of treatment (time 0) and at 24 and 72 hours for a CBC, measurement of fibrinogen concentration, coagulation screening tests, and a panel of assays to assess platelet activation (including ADP- and collagen-induced aggregation and closure times, flow-cytometric variables of platelet-leukocyte aggregates, platelet membrane P-selectin and phosphatidylserine expression, and microparticle release), von Willebrand factor (vWF) concentration, and cofactor activity. In addition, thrombelastography was used to evaluate fibrin formation in tissue factor–activated whole blood and plasma and to assess tissue plasminogen activator–induced plasma fibrinolysis. For each treatment, values obtained before and 72 hours after start of administration were compared by use of Wilcoxon signed rank tests.
RESULTS Yunnan Baiyao treatment had no significant effect on any hemostatic variable, compared with results for the placebo treatment.
CONCLUSIONS AND CLINICAL RELEVANCE Administration of Yunnan Baiyao at a dosage typically used in clinical practice had no effect on in vitro measures of platelet or vWF function and no enhancement of fibrin-clot formation or stability. Any hemostatic actions of Yunnan Baiyao may require higher dosages or result from cell-surface interactions at sites of vascular and tissue injury not examined in this study.
OBJECTIVE To evaluate the effects of treatment of horses with standard platelet inhibitors on ex vivo inhibition of platelet activation by equine herpesvirus type I (EHV-I).
ANIMALS II healthy adult horses.
PROCEDURES In a double-blinded, placebo-controlled crossover study, horses were treated orally for 5 days with theophylline (5 mg/kg, q 12 h), pentoxifylline (10 mg/kg, q 12 h), clopidogrel bisulfate (4 mg/kg, q 24 h), acetylsalicylic acid (20 mg/kg, q 24 h), or placebo. Horses received all treatments, each separated by a 3-week washout period. Platelet-rich plasma was prepared from citrated blood samples obtained before each treatment session and 4 hours after each final drug dose. Platelets were exposed to 2 EHV-I strains (at I plaque forming units/cell) or positive (thrombin-convulxin) and negative control substances for 10 minutes, then platelet activation was assessed by determining the percentages of P-selectin–positive platelets and platelet-derived microparticles (PDMPs; small events positive for annexin V) with flow cytometry. Platelet aggregation in response to 10μM ADP was also assessed.
RESULTS No significant differences in median percentages of P-selectin–positive platelets and PDMPs in EHV-I-exposed platelets were identified between measurement points (before and after treatment) for all drugs, nor were differences identified among drugs at each measurement point. Only clopidogrel significantly inhibited platelet aggregation in response to ADP in platelet-rich plasma samples obtained after that treatment session.
CONCLUSIONS AND CLINICAL RELEVANCE Treatment of horses with standard platelet inhibitors had no effect on EHV-I-induced platelet α-granule exteriorization or microvesiculation and release of PDMPs ex vivo, suggesting these drugs will not prevent platelet activation induced directly by EHV-I in vivo.
Objective—To compare effects of 3 methods of topically applied cold treatment (cryotherapy) on digital laminar and venous temperatures in horses.
Animals—9 healthy adult Thoroughbreds.
Procedures—Thermocouples were placed in palmar digital veins and digital laminae of both forelimbs of horses. Three methods of cryotherapy were applied to the distal aspects of the limbs: wader boot (63-cm-tall vinyl boot filled with ice and water [ice slurry]), ice bag (5-L fluid bag filled with ice slurry), and a gel pack boot (boot containing frozen gel packs). Gel packs and ice slurries were replenished every hour during cryotherapy. The forelimb that received the first treatment was randomly assigned; thereafter, control and treated forelimbs were alternated for each treatment. For each treatment, temperatures were recorded every minute during 15-minute pretreatment, 2-hour treatment, and ≥ 30 minute rewarming periods. Once temperatures had returned to within 3°C below pretreatment values, the experiment was repeated in a similar manner for other cryotherapy methods.
Results—Digital venous temperatures were similar to laminar temperatures during each treatment. Ice bag and wader boot treatments caused similar cooling of digits. Gel boot treatment did not cause substantial cooling of digits.
Conclusions and Clinical Relevance—Ice bag treatment caused laminar and digital venous cooling equivalent to that of wader boot treatment. Cryotherapy by use of 5-L fluid bags with an ice slurry may be a readily available, practical, and efficient method for prevention of laminitis in horses. Digital laminar and venous temperatures were similar in forelimbs of horses before and during cryotherapy.