Clinical effect of torsemide in a horse with congestive heart failure and atrial fibrillation.

In this case report, a high dose of torsemide (6mg/kg, every 12 hours for 3 days followed by 12mg/kg, every 12 hours for 4 days) was administered orally to a horse with congestive heart failure (CHF) and atrial fibrillation. Blood samples for measurement of plasma torsemide concentrations were obtained one hour after each drug administration. Pharmacodynamic effects of oral torsemide were evaluated by daily physical examination, electrocardiography, and serum biochemistry. The horse tolerated administration of torsemide. A decrease in ventral oedema and venous congestion was subjectively noted at day 7. Torsemide plasma concentration markedly increased at day 5 (peak concentration of 15.41 µg/mL). Evidence of an increase in renal markers was observed throughout the study period. Electrolyte measurements revealed mild hyponatremia and hypochloremia, and moderate hypokalaemia. No electrocardiographic changes related to torsemide administration were observed. After seven days of treatment, the horse was euthanised due to his disease stage and poor prognosis. Results indicate that torsemide was absorbed after oral administration and was well tolerated in this horse. Furthermore, clinical improvement in this single case indicates that torsemide might be utilized as an oral alternative to furosemide in the management of equine patients in CHF. The high doses of torsemide used in this case report should be reserved for cases without clinical response to lower doses and with close monitoring of electrolytes and renal function parameters. Further investigation of torsemide clinical efficacy and safety in horses with CHF with a larger cohort and prolonged administration is warranted.

Disposition of levetiracetam in healthy adult horses.

Nine horses received 20 mg/kg of intravenous (LEVIV ); 30 mg/kg of intragastric, crushed immediate release (LEVCIR ); and 30 mg/kg of intragastric, crushed extended release (LEVCER ) levetiracetam, in a three-way randomized crossover design. Crushed tablets were dissolved in water and administered by nasogastric tube. Serum samples were collected over 48 hr, and levetiracetam concentrations were determined by immunoassay. Mean ± SD peak concentrations for LEVCIR and LEVCER were 50.72 ± 10.60 and 53.58 ± 15.94 µg/ml, respectively. The y-intercept for IV administration was 64.54 ± 24.99 µg/ml. The terminal half-life was 6.38 ± 1.97, 7.07 ± 1.93 and 6.22 ± 1.35 hr for LEVCIR , LEVCER, and LEVIV , respectively. Volume of distribution at steady-state was 630 ± 73.4 ml/kg. Total body clearance after IV administration was 74.40 ± 19.20 ml kg-1  hr-1 . Bioavailability was 96 ± 10, and 98 ± 13% for LEVCIR and LEVCER , respectively. A single dose of Levetiracetam (LEV) was well tolerated. Based on this study, a recommended dosing regimen of intravenous or oral LEV of 32 mg/kg every 12 hr is likely to achieve and maintain plasma concentrations within the therapeutic range suggested for humans, with optimal kinetics throughout the dosing interval in healthy adult horses. Repeated dosing and pharmacodynamic studies are warranted.

Effect of Age, Season, Body Condition, and Endocrine Status on Serum Free Cortisol Fraction and Insulin Concentration in Horses.

BACKGROUND: Increased free cortisol fraction is associated with insulin dysregulation (ID) in people with Metabolic Syndrome and Cushing's Disease. Free cortisol has not been investigated in equine endocrine disorders. HYPOTHESES: (1) In healthy horses, sex, age, body condition score (BCS), and season impact free cortisol; (2) free cortisol is increased in horses with Pituitary Pars Intermedia Dysfunction (PPID) or Equine Metabolic Syndrome (EMS). ANIMALS: Fifty-seven healthy horses; 40 horses and ponies with PPID (n = 20) or EMS (n = 20). METHODS: Prospective study. Serum collected seasonally from healthy animals and archived serum from PPID and EMS animals was analyzed for insulin, total and free cortisol concentrations, and free cortisol fraction (FCF). Linear mixed models were used to determine effects of age, sex, season, and BCS on hormones in controls. Hormone measurements were compared between disease groups and age- and season-matched controls with t-tests. EMS and hyperinsulinemic PPID animals were combined in an ID (hyperinsulinemia) group. RESULTS: Free cortisol concentrations were increased in overweight/obese controls (0.3 ± 0.1 µg/dL) compared to lean controls (0.2 ± 0.1 µg/dL; P = .017). Mean FCF was significantly higher in animals with PPID (8.8 ± 5.8 µg/dL, P = .005) or ID (8.8 ± 10.2 µg/dL, P = .039) than controls (5.0 ± 0.9 µg/dL), but total cortisol concentrations were similar (P ≥ .350) (PPID: 4.2 ± 4.3 µg/dL; ID: 5.0 ± 4.5 µg/dL; controls: 4.6 ± 1.7 and 5.1 ± 2.1 µg/dL). CONCLUSIONS AND CLINICAL IMPORTANCE: Increased FCF is associated with obesity in healthy horses and with ID (hyperinsulinemia) in horses and ponies with endocrine disease. Decreased plasma cortisol-binding capacity could be a component of these endocrine disorders in horses.

Experimental transmission of Corynebacterium pseudotuberculosis biovar equi in horses by house flies.

BACKGROUND: The route of Corynebacterium pseudotuberculosis infection in horses remains undetermined, but transmission by insects is suspected. OBJECTIVES: To investigate house flies (Musca domestica L.) as vectors of C. pseudotuberculosis transmission in horses. ANIMALS: Eight healthy, adult ponies. METHODS: Randomized, controlled, blinded prospective study. Ten wounds were created in the pectoral region where cages for flies were attached. Three ponies were directly inoculated with C. pseudotuberculosis. Four ponies were exposed for 24 hours to 20 hours C. pseudotuberculosis-inoculated flies. One negative control pony was exposed to noninoculated flies. Ponies were examined daily for swelling, heat, pain, and drainage at the inoculation site. Blood was collected weekly for CBC and biochemical analysis, and twice weekly for synergistic hemolysis inhibition titers. RESULTS: Clinical signs of local infection and positive cultures were observed in 7/7 exposed ponies and were absent in the negative control. In exposed ponies, peak serologic titers (1:512 to 1:2,048) were obtained between days 17 and 21. Seroconversion was not observed in the negative control. Neutrophil counts were higher in the positive and fly-exposed groups than in the negative control (P = .002 and P = .005) on day 3 postinoculation. Serum amyloid A concentrations were higher in the positive control than in the negative control and fly-exposed ponies on days 3 (P < .0001) and 7 (P = .0004 and P = .0001). No differences were detected for other biochemical variables. CONCLUSIONS AND CLINICAL IMPORTANCE: House flies can serve as mechanical vectors of C. pseudotuberculosis and can transmit the bacterium to ponies.

Vasorelaxation responses to insulin in laminar vessel rings from healthy, lean horses.

Hyperinsulinemia causes laminitis experimentally and is a risk factor for naturally occurring laminitis. The aim of this study was to investigate the effects of insulin on laminar vascular relaxation and to induce insulin-associated vascular dysfunction in vitro. Relaxation responses of isolated laminar arterial and venous rings to acetylcholine and insulin were evaluated. To alter vascular function in response to insulin, all vessel rings were incubated with insulin or vehicle, submaximally contracted, administered insulin again and relaxation responses recorded. Laminar arteries were also incubated with the mitogen-activated protein kinase (MAPK) inhibitor, PD-98059. Relaxation in response to acetylcholine was not different between arteries and veins, but veins relaxed less in response to insulin than arteries. In arteries incubated with insulin, the subsequent relaxation response to insulin was blunted. Veins had minimal relaxation to insulin regardless of incubation. Arteries incubated with PD-98059 relaxed more in response to insulin than arteries not exposed to PD-98059, indicating that MAPK plays a role in maintenance of basal tone in laminar arteries. A differing response of laminar veins and arteries to insulin-induced relaxation may be important in understanding the link between hyperinsulinemia and laminitis. In vitro induction of vascular dysfunction in response to insulin in laminar arteries may be useful for testing therapeutic interventions and for understanding the pathophysiology of laminitis.

Seasonal changes in the combined glucose-insulin tolerance test in normal aged horses.

BACKGROUND: Equine metabolic syndrome (EMS) is an increasingly recognized problem in adult horses. Affected horses are often obese and predisposed to the development of laminitis, especially in the spring and summer months. In addition, in the summer and fall months, increases in endogenous insulin concentrations, a marker of EMS, have been reported. HYPOTHESIS/OBJECTIVES: The purpose of this study was to evaluate seasonal changes in results of the combined glucose-insulin tolerance test (CGIT), a diagnostic test for EMS. ANIMALS: Nine healthy, aged horses with no history of laminitis and no clinical signs of EMS. METHODS: Horses were given dextrose (150 mg/kg) and insulin (0.1 U/kg) IV. Plasma glucose concentrations were measured at 0, 1, 5, 15, 30, 45, 60, 75, 90, and 150 minutes and serum insulin concentrations at 0, 5, and 75 minutes. Testing was performed in February, May, June, August, September, and November. Mean glucose concentrations, characteristics of the curve, and insulin concentrations during the CGIT were compared across months using repeated measures ANOVA (P < .05). RESULTS: No CGIT parameters indicated insulin resistance, but mean area under the curve for glucose concentrations was significantly lower in August and November compared to February and in November compared to June, indicating increased insulin-mediated glucose clearance. Glucose nadir was significantly lower in November compared to that in February. CONCLUSIONS AND CLINICAL IMPORTANCE: No clinically relevant differences were seen in the results of the CGIT, suggesting that season minimally affects results of this test in normal aged horses in the southeastern United States.

Seasonal changes in plasma adrenocorticotropic hormone and α-melanocyte-stimulating hormone in response to thyrotropin-releasing hormone in normal, aged horses.

BACKGROUND: Results of diagnostic tests for equine pituitary pars intermedia dysfunction (PPID), including endogenous ACTH concentration and the overnight dexamethasone suppression test (DST), are affected by season. New and potentially more sensitive diagnostic tests for equine PPID, such as thyrotropin-releasing hormone (TRH)-stimulated ACTH response, have been developed, but have had limited evaluation of seasonality. OBJECTIVE: Our purpose was to evaluate seasonal changes in plasma ACTH and alpha-melanocyte-stimulating hormone (α-MSH) responses to TRH administration. ANIMALS: Nine, healthy, aged horses with normal DST results. METHODS: Synthetic TRH (1 mg) was administered IV. Plasma ACTH and α-MSH concentrations were measured at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 180 minutes. Testing was performed in February, July, August, September, October, and November. Mean TRH-stimulated ACTH and α-MSH concentrations were compared across months and time by repeated measures analysis of variance. Significance was set at the P < .05 level. RESULTS: Concentrations of ACTH and α-MSH significantly increased after TRH administration. Endogenous and TRH-stimulated ACTH and α-MSH concentrations were significantly different across months with higher concentrations in the summer and fall compared with February. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma ACTH and α-MSH responses to TRH administration experience seasonal variation, with TRH-stimulated ACTH and α-MSH concentrations increasing from summer through fall. These results support previous evidence of a seasonal influence on the equine pituitary-adrenal axis. More research is warranted with a larger number of horses to determine if seasonal reference ranges for TRH stimulation testing need to be defined.

Gynecomastia and mammary gland adenocarcinoma in a Nubian buck.

A 6-year-old Nubian buck was presented for bilateral mammary gland enlargement. Gynecomastia and mastitis were diagnosed, and bilateral mastectomy was performed. Histological examination showed mammary adenocarcinoma, active lactation, hyperplasia, and abscessation. Karyotyping showed a normal male. Clinical, therapeutic, etiologic, and epidemiologic aspects of gynecomastia and mammary gland adenocarcinoma are discussed.

Chronic renal failure associated with nephrolithiasis, ureterolithiasis, and renal dysplasia in a 2-year-old quarter horse gelding.

A 2-year-old quarter horse gelding presented for evaluation of polyuria and polydipsia. Azotemia was detected on serum chemistry profile. Small, misshapen, hyperechoic kidneys with decreased corticomedullary demarcation, hydronephrosis, and a right nephrolith were noted ultrasonographically. The diagnosis of end-stage kidney disease and dysplasia was made histopathologically using ultrasound-guided biopsy. Two ureteroliths were found in the right ureter via cystoscopy, and a nephrolith was seen in the right kidney at necropsy. Clinical, ultrasonographic, and pathologic features of equine urolithiasis and renal dysplasia are discussed.

Neuromuscular effects of doxacurium chloride in isoflurane-anesthetized dogs.

OBJECTIVE: To determine the neuromuscular effects of doxacurium chloride and to construct a dose-response curve for the drug in isoflurane-anesthetized dogs. DESIGN: Randomized, controlled trial. ANIMALS: Six healthy, adult, mixed-breed dogs (five female, one male) weighing 24.8 +/- 2.8 kg. METHODS: Anesthesia was induced with isoflurane in oxygen and maintained with 1.9% to 2.3% end-tidal isoflurane concentration. PaCO2 was maintained between 35 and 45 mm Hg with mechanical ventilation. Mechanomyography was used to quantitate the evoked twitch response of the paw after supramaximal train-of-four stimulation of the superficial peroneal nerve. After baseline values were recorded, the dogs received one of three doses of doxacurium (2.0, 3.5, 4.5 microg/kg of body weight) or a saline placebo intravenously in random order. All dogs received all treatments with at least 7 days between studies. After drug administration, the degree of maximal first twitch depression compared with baseline (T1%) was recorded. Dose-response relations of doxacurium were plotted in log dose-probit format and analyzed by linear regression to determine effective dose (ED50 and ED90) values for doxacurium. RESULTS: The median log dose-probit response curve showed good data correlation (r = .999) with estimates of the ED50 (2.1 microg/kg) and ED90 (3.5 microg/kg) for doxacurium in isoflurane-anesthetized dogs. Mean +/- SD values for T1% (first twitch tension compared with baseline) at maximal depression after drug administration, onset (time from drug administration to maximal depression of T1%), duration (time from maximal depression of T1% to 25% recovery of T1%), and recovery (time from 25% to 75% recovery of T1%) times were 92% +/- 4%, 40 +/- 5 minutes, 108 +/- 31 minutes, and 42 +/- 11 minutes for dogs treated with 3.5 microg/kg of doxacurium and 94% +/- 7%, 41 +/- 8 minutes, 111 +/- 33 minutes, and 37 +/- 10 minutes for dogs treated with 4.5 microg/kg of doxacurium. CONCLUSION AND CLINICAL RELEVANCE: We conclude that doxacurium is a long-acting neuromuscular blocking agent with a slow onset of action. Doxacurium can be used to provide muscle relaxation for long surgical procedures in isoflurane-anesthetized dogs. Interpatient variability, particularly of duration of drug action, may exist in the neuromuscular response to the administration of doxacurium in dogs.

Effect of ketorolac tromethamine on atracurium-induced neuromuscular blockade in anesthetized dogs.

OBJECTIVE: The purpose of this study was to determine the effect of ketorolac tromethamine or placebo on the neuromuscular blockade induced by an infusion of atracurium in isoflurane-anesthetized dogs. DESIGN: Randomized, controlled trial. ANIMALS: Six healthy, adult mixed-breed dogs (five female, one male) weighing 24.8 +/- 2.8 kg. METHODS: Dogs were studied on two occasions with a minimum of 7 days between studies. Dogs were induced with 5% isoflurane in oxygen and maintained with 1.6 x minimum alveolar concentration (MAC) end-tidal isoflurane. Neuromuscular blockade was assessed using the train-of-four response. Once 50% depression of the first twitch (T1) was achieved, the atracurium infusion rate was held constant for 30 minutes. Then ketorolac, 0.5 mg/kg, or the same volume of placebo (0.9% sodium chloride solution) was administered intravenously and the atracurium infusion maintained for an additional 60 minutes. Before and at 2, 5, 10, 15, 30, and 60 minutes after ketorolac or placebo, the percent depression of T1 and the fourth twitch to the first twitch (T4/T1) ratio were recorded. The atracurium infusion was discontinued and the time for T1 to recover from 50% to 75% of its original value was recorded. At 75% T1, edrophonium, 0.5 mg/kg intravenously, was administered to antagonize the residual blockade. RESULTS: There was no significant difference in T1%, T4/T1 ratio, or recovery time after ketorolac administration compared with placebo. CONCLUSIONS: Ketorolac, 0.5 mg/kg intravenously, has no significant effect on either atracurium-induced neuromuscular blockade or recovery time for T1 in isoflurane-anesthetized dogs. CLINICAL RELEVANCE: The concurrent use of atracurium should not be a contraindication for the administration of ketorolac for intraoperative or postoperative analgesia.

Pharmacokinetics, effects on renal function, and potentiation of atracurium-induced neuromuscular blockade after administration of a high dose of gentamicin in isoflurane-anesthetized dogs.

OBJECTIVE: To determine pharmacokinetics, renal effects, and effect on atracurium-induced neuromuscular blockade of a high dose of gentamicin in isoflurane-anesthetized dogs. ANIMALS: 6 healthy, adult, mixed-breed dogs, anesthetized twice and receiving gentamicin (6 mg/kg of body weight, i.v.) or saline solution. PROCEDURE: Blood samples were collected before and at intervals after gentamicin administration. Pharmacokinetic values were evaluated by use of multivariant stepwise linear regression analysis. Gentamicin-induced renal changes were assessed by comparing pretreatment and 12- to 24-hour posttreatment values for serum urea nitrogen, serum creatinine, urine creatinine-to-gamma-glutamyl-transferase ratio, and urinalysis. Neuromuscular blockade, maintained by atracurium infusion, was assessed, using the train-of-four response. At stable 50% depression of first twitch (T1), gentamicin or saline solution was given. Before and at posttreatment intervals for 60 minutes, T1% and fourth twitch-to-T1 ratio were recorded. The infusion was discontinued and 50 to 75% T1 recovery time was recorded. At 75% T1, edrophonium (0.5 mg/kg) was administered i.v.. RESULTS: Mean values for volume of distribution and clearance were 0.263 L/kg and 2.0 ml/min/kg, respectively. Mean maximal serum concentration of gentamicin was 46.4 micrograms/ml. Pre and posttreatment values for serum urea nitrogen, serum creatinine, urine creatinine-to-gamma-glutamyltransferase ratio, and other urine analytes were not significantly different. Mean (+/- SD) values for T1% and fourth twitch-to-T1 ratio decreased significantly after gentamicin (depression was maximal at 5 minutes). Recovery time (50 to 75% T1) was not different between groups. Edrophonium restored twitch to baseline. CONCLUSIONS: Mean values for apparent volume of distribution and total body clearance of gentamicin were similar to values in unanesthetized dogs. Mean maximal serum concentration of gentamicin was greater than that in unanesthetized dogs. Renal function was unaffected. Gentamicin potentiated atracurium-induced neuromuscular blockade, but did not affect recovery time.