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.

Objective-To evaluate antinociceptive and selected effects associated with IM administration of xylazine hydrochloride in combination with tiletamine-zolazepam in llamas. Animals-8 adult male llamas. Procedures-Each llama received tiletamine-zolazepam (2 mg/kg) combined with either xylazine (0.1, 0.2, or 0.4 mg/kg) or saline (0.9% NaCl) solution IM (treatments designated as TZ-Xy0.1, TZ-Xy0.2, TZ-Xy0.4, and TZ-Sal, respectively) at 1-week intervals. Selected cardiorespiratory variables were assessed during lateral recumbency and anesthesia, and recovery characteristics were recorded. Duration of antinociception was evaluated by clamping a claw every 5 minutes. Results-Interval between treatment administration and lateral recumbency for TZ-Xy0.4 was shorter than that for TZ-Xy0.1 or TZ-Sal. Mean ± SEM duration of antinociception was longer for TZ-Xy0.4 (51.3 +/- 7. 0 minutes), compared with findings for TZ-Xy0.2 (31.9 +/- 6.0 minutes), TZ-Xy0.1 (8.1 +/- 4.0 minutes), and TZ-Sal (0.6 +/- 0.6 minutes). Interval between treatment administration and standing was longer for TZ-Xy0.4 (112 +/- 9 minutes) than it was for TZ-Xy0.2 (77 +/- 9 minutes) or TZ-Sal (68 +/- 9 minutes). Mean heart and respiratory rates during the first 30 minutes for TZ-Sal exceeded values for the other treatments. Administration of TZ-Xy0.2 and TZ-Xy0.4 resulted in Pao2 < 60 mm Hg at 5 minutes after llamas attained lateral recumbency, and values differed from TZ-Sal findings at 5, 10, and 15 minutes; Paco2 was greater for TZ-Xy0.2 and TZ-Xy0.4 than for TZ-Sal at 5, 10, 15, and 20 minutes. Conclusions and Clinical Relevance—Xylazine (0.2 and 0.4 mg/kg) increased the duration of antinociception in llamas anesthetized with tiletamine-zolazepam.

Objective—To determine the cardiopulmonary effects of 3 doses of isoflurane, with and without controlled mechanical ventilation and noxious stimulation, in healthy adult New Zealand white rabbits. Animals—6 adult female rabbits. Procedures—Each rabbit was administered isoflurane in oxygen at each of 3 anesthetic doses (1.0, 1.5, or 2.0 times the published minimum alveolar concentration of 2.07%). At each anesthetic dose, blood gas and cardiopulmonary measurements were obtained before and during application of a supramaximal noxious stimulus. Effects of spontaneous and mechanical ventilation were assessed during separate anesthetic episodes. Results—Mean ± SEM isoflurane concentrations used were 2.11 ± 0.04%, 3.14 ± 0.07%, and 4.15 ± 0.06%. During spontaneous ventilation, the rabbits’ Paco2 and mixed venous Pco2 significantly increased with concomitant reductions in both arterial and mixed venous pH as isoflurane concentration increased. Cardiac output and vascular resistance did not change significantly. Noxious stimulation minimally affected measured cardiopulmonary variables. During mechanical ventilation, significant reductions in arterial blood pressures and cardiac output occurred with increasing isoflurane dose. Systemic vascular resistance index at the highest anesthetic dose was significantly lower than the value at the lowest anesthetic dose. During noxious stimulation, systolic arterial blood pressure and cardiac output significantly increased at the 2 lower isoflurane concentrations, but not at the highest concentration. Conclusions and Clinical Relevance—In rabbits, isoflurane-induced dose-dependent cardiopulmonary depression was attributable to vasodilation and negative inotropy. At an isoflurane concentration of 4.15% with mechanical ventilation, cardiovascular depression was severe; use of unnecessarily high isoflurane concentrations in this species should be avoided.

Objective—To assess the anesthetic efficacy and local tolerance of topically applied 0.4% oxybuprocaine ophthalmic solution to in dogs and compare its effects with those of 1% tetracaine solution. Animals—34 ophthalmically normal Beagles. Procedures—Dogs were assigned to 2 groups, and baseline corneal touch threshold (CTT) was measured bilaterally with a Cochet-Bonnet aesthesiometer. Dogs of group 1 (n = 22) received a single drop of 0.4% oxybuprocaine ophthalmic solution in one eye and saline (0.9% NaCl) solution (control treatment) in the contralateral eye. Dogs of group 2 (n = 12) received a single drop of 0.4% oxybuprocaine ophthalmic solution in one eye and 1% tetracaine ophthalmic solution in the contralateral eye. The CTT of each eye was measured 1 and 5 minutes after topical application and then at 5-minute intervals until 75 minutes after topical application. Results—CTT changes over time differed significantly between oxybuprocaine-treated and control eyes. After instillation of oxybuprocaine, maximal corneal anesthesia (CTT = 0) was achieved within 1 minute, and CTT was significantly decreased from 1 to 45 minutes, compared with the baseline value. No significant difference in onset, depth, and duration of corneal anesthesia was found between oxybuprocaine-treated and tetracaine-treated eyes. Conjunctival hyperemia and chemosis were detected more frequently in tetracaine-treated eyes than in oxybuprocaine-treated eyes. Conclusions and Clinical Relevance—Topical application of oxybuprocaine and tetracaine similarly reduced corneal sensitivity in dogs, but oxybuprocaine was less irritating to the conjunctiva than was tetracaine.

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.

Objective-To evaluate the duration of effects on movement patterns of horses after sedation with equipotent doses of xylazine hydrochloride, detomidine hydrochloride, or romifidine hydrochloride and determine whether accelerometry can be used to quantify differences among drug treatments. Animals-6 healthy horses. Procedures-Each horse was injected IV with saline (0.9% NaCl) solution (10 mL), xylazine diluted in saline solution (0.5 mg/kg), detomidine diluted in saline solution (0.01 mg/kg), or romifidine diluted in saline solution (0.04 mg/kg) in random order. A triaxial accelerometric device was used for gait assessment 15 minutes before and 5, 15, 30, 45, 60, 75, 90, 105, and 120 minutes after each treatment. Eight variables were calculated, including speed, stride frequency, stride length, regularity, dorsoventral power, propulsive power, mediolateral power, and total power; the force of acceleration and 3 components of power were then calculated. Results-Significant differences were evident in stride frequency and regularity between treatments with saline solution and each α2-adrenoceptor agonist drug; in speed, dorsoventral power, propulsive power, total power, and force values between treatments with saline solution and detomidine or romifidine; and in mediolateral power between treatments with saline solution and detomidine. Stride length did not differ among treatments. Conclusions and Clinical Relevance-Accelerometric evaluation of horses administered α2-adrenoceptor agonist drugs revealed more prolonged sedative effects of romifidine, compared with effects of xylazine or detomidine. Accelerometry could be useful in assessing the effects of other sedatives and analgesics. Accelerometric data may be helpful in drug selection for situations in which a horse's balance and coordination are important.

A temporal study was carried out to determine Salmonella prevalence, trends, major serovars, and their clusters from environmental samples, in poultry breeder flocks in Ontario between January 1998 and December 2008. Surveillance data were obtained from the Ontario Hatchery and Supply Flock Policy. Logistic regression with a random effect for flock was used to identify factors [poultry type, year (trend) and season] associated with the prevalence of Salmonella. A cluster detection test was used to identify clusters of common serovars. The period prevalence of Salmonella was 47.4% in broiler-breeder, 25.7% in layer-breeder, and 19.6% in turkey-breeder flocks. The overall trend in the prevalence of Salmonella was decreasing for all breeder types, due primarily to decreasing trends of Salmonella Heidelberg. The seasonal effects varied by year with the highest probability of Salmonella occurring in different seasons. The 4 most common serovars identified were Salmonella Heidelberg, Kentucky, Hadar, and Typhimurium in broiler-breeders; Salmonella Heidelberg, Brandenburg, Thompson, and Typhimurium in layer-breeders; and Salmonella Heidelberg, Saintpaul, Brandenburg, and Muenster in turkey-breeders. Salmonella Enteritidis was infrequently isolated in all poultry breeder types. Temporal clusters of different serovars were identified in all poultry breeder types. Clusters of Salmonella Heidelberg, Typhimurium, and Hadar from environmental samples from breeder flocks were detected during a similar period to clusters from hatchery fluff samples from the same population. Therefore, interventions at the breeder flock-level might help to reduce transmission of Salmonella from breeder flocks to hatcheries and possibly, to lower levels of the poultry production chain.

Objective-To compare quantitative magnetic resonance (QMR), dual-energy x-ray absorptiometry (DXA), and deuterium oxide (D2O) methods for measurement of total body water (TBW), lean body mass (LBM), and fat mass (FM) in healthy dogs and to assess QMR accuracy. Animals-58 Beagles (9 months to 11.5 years old). Procedures-QMR scans were performed on awake dogs. A D2O tracer was administered (100 mg/kg, PO) immediately before dogs were sedated, which was followed by a second QMR or DXA scan. Jugular blood samples were collected before and 120 minutes after D2O administration. Results-TBW, LBM, and FM determined via QMR were not significantly different between awake or sedated dogs, and means differed by only 2.0%, 2.2%, and 4.3%, respectively. Compared with results for D2O dilution, QMR significantly underestimated TBW (10.2%), LBM (13.4%), and FM (15.4%). Similarly, DXA underestimated LBM (7.3%) and FM (8.4%). A significant relationship was detected between FM measured via D2O dilution and QMR (r2 > 0.89) or DXA (r2 > 0.88). Even though means of TBW and LBM differed significantly between D2O dilution and QMR or DXA, values were highly related (r2 > 0.92). Conclusions and Clinical Relevance-QMR was useful for determining body composition in dogs and can be used to safely and rapidly acquire accurate data without the need for sedation or anesthesia. These benefits can facilitate frequent scans, particularly in geriatric, extremely young, or ill pets. Compared with the D2O dilution method, QMR correction equations provided accurate assessment over a range of body compositions.

Objective: To compare the degree of mRNA expression for matrix metalloproteinases (MMPs), tissue inhibitors (TIMPs), and lysyl oxidase in myocardial samples from dogs with cardiac and systemic diseases and from healthy control dogs. Sample: Myocardial samples from the atria, ventricles, and septum of 8 control dogs, 6 dogs with systemic diseases, 4 dogs with dilated cardiomyopathy (DCM), and 5 dogs with other cardiac diseases. Procedures: Degrees of mRNA expression for MMP-1, -2, -3, -9, and -13; TIMP-1, -2, -3, and -4; and lysyl oxidase were measured via quantitative real-time PCR assay. Histologic examination of the hearts was performed to identify pathological changes. Results: In myocardial samples from control dogs, only TIMP-3 and TIMP-4 mRNA expression was detected, with a significantly higher degree in male versus female dogs. In dogs with systemic and cardiac diseases, all investigated markers were expressed, with a significantly higher degree of mRNA expression than in control dogs. Furthermore, the degree of expression for MMP-2, TIMP-1, and TIMP-2 was significantly higher in dogs with DCM than in dogs with systemic diseases and cardiac diseases other than DCM. Expression was generally greater in atrial than in ventricular tissue for MMP-2, MMP-13, and lysyl oxidase in samples from dogs with atrial fibrillation. Conclusions and Clinical Relevance: Degrees of myocardial MMP, TIMP, and lysyl oxidase mRNA expression were higher in dogs with cardiac and systemic diseases than in healthy dogs, suggesting that expression of these markers is a nonspecific consequence of end-stage diseases. Selective differences in the expression of some markers may reflect specific pathogenic mechanisms and may play a role in disease progression, morbidity and mortality rates, and treatment response.

Objective: To compare immune responses following modified-live virus (MLV) vaccination at weaning after intranasal or SC administration of an MLV vaccine to beef calves at 2 or 70 days of age. Animals: 184 calves. Procedures: Calves were allocated to 1 of 5 groups. The IN2 (n = 37) and IN70 (37) groups received an MLV vaccine containing bovine herpesvirus 1 (BHV1), bovine viral diarrhea virus (BVDV) types 1 and 2, bovine respiratory syncytial virus (BRSV), and parainfluenza 3 virus intranasally and a Mannheimia haemolytica and Pasteurella multocida bacterin SC at median ages of 2 and 70 days, respectively. The SC2 (n = 36) and SC70 (37) groups received a 7-way MLV vaccine containing BHV1, BVDV1, BVDV2, BRSV, parainfluenza 3 virus, M haemolytica, and P multocida SC at median ages of 2 and 70 days, respectively; the control group (37) remained unvaccinated until weaning. All calves received the 7-way MLV vaccine SC at median ages of 217 (weaning) and 231 days. Serum neutralizing antibody (SNA) titers against BHV1, BVDV1, and BRSV and intranasal IgA concentrations were determined at median ages of 2, 70, 140, 217, and 262 days. Cell-mediated immunity (CMI) against BHV1, BRSV, BVDV1, and P multocida was determined for 16 calves/group. Results: At median ages of 140 and 217 days, BVDV1 SNA titers were significantly higher for the SC70 group than those for the other groups. Intranasal IgA concentrations and CMI increased over time for all groups. Vaccination at weaning increased SNA titers and CMI in all groups. Conclusions and Clinical Relevance: SC administration of an MLV vaccine to 70-day-old calves significantly increased BVDV1 antibody titers before weaning.