Objective: To evaluate the pharmacodynamic effects of dalteparin in dogs by means of viscoelastic coagulation monitoring with a thromboelastograph and a dynamic viscoelastic coagulometer. Animals: 6 healthy adult mixed-breed dogs. Procedures: Dalteparin (175 U/kg, SC, q 12 h) was administered for 4 days (days 1 through 4). Viscoelastic coagulation monitoring was performed hourly on the first and last days of treatment and included intermittent measurement of anti–activated coagulation factor X activity (AXA). Results: Dalteparin administration resulted in progressive hypocoagulability. On both day 1 and 4, activated clotting time and clot rate for the dynamic viscoelastic coagulometer differed significantly from baseline values, whereas the platelet function parameter did not change on day 1 but did on day 4. The R (reaction time), time from reaction time until the amplitude of the thromboelastography tracing is 20 mm, α-angle, and maximum amplitude differed from baseline values on days 1 and 4, although many thromboelastographic variables were not determined. The AXA was increased from baseline values at 3 and 6 hours after administration of the dalteparin injection on days 1 and 4, and all dogs had AXA values between 0.5 and 1.0 U/mL at 2 and 4 hours after administration. The AXA correlated well with activated clotting time (r = 0.761) and with R (r = 0.810), when values were available. Thromboelastography could not be used to distinguish AXA > 0.7 U/mL. Conclusions and Clinical Relevance: Viscoelastic coagulation monitoring with strong coagulation activators may be used to monitor treatment with dalteparin in healthy dogs.

Objective--To determine whether larkspur-derived N-(methylsuccinimido) anthranoyllycoctonine (MSAL)-type alkaloids alter heart rate and electrically evoked electromyographic (eEMG) response of the external anal sphincter (EAS) in cattle and whether these effects can be reversed by acetylcholinesterase inhibitors. Animals--12 beef heifers and 4 cows. Procedures--3 or 4 heifers were used in 1 or 2 of 7 dose-response experiments; heart rate and EAS eEMG response were assessed before and 24 hours after oral treatment with larkspur (doses equivalent to 0.5 to 15 mg of MSAL-type alkaloids/kg). In 3 subsequent experiments, 3 heifers (1 of which was replaced with another heifer in the control experiment) each received 10 mg of MSAL-type alkaloids/kg and were injected IV with physostigmine (0.04 mg/kg), neostigmine (0.04 mg/kg), or saline (0.9% NaCl) solution 24 hours later, prior to assessment. Additionally, EAS eEMG response was measured in 4 cows before and after epidural administration of 2% lidocaine hydrochloride. Results--Larkspur-treated heifers developed dose-related increases in heart rate and decreases in EAS eEMG response. Twenty-four hours after administration of MSAL-type alkaloids, neostigmine decreased heart rate but did not affect eEMG response, whereas physostigmine did not affect heart rate but caused a 2-fold increase in eEMG response. In cows, epidural anesthesia did not alter eEMG response, suggesting that transdermal stimulation of the EAS pudendal innervation did not occur. Conclusions and Clinical Relevance--In cattle, cardiac effects and muscle weakness or loss of EAS eEMG response induced by larkspur-derived MSAL-type alkaloids were reversed by neostigmine or physostigmine, respectively. Treatment with anticholinesterase inhibitors may alter the clinical effects of larkspur poisoning in cattle.

Objective-To assess gait abnormalities associated with selective anesthesia of the suprascapular nerve (SSN) achieved by use of perineural catheterization and thereby determine the function of that nerve as it relates to gait in horses. Animals-3 adult horses with no preexisting clinically apparent lameness at a walk. Procedure-Each horse was anesthetized; the right SSN was exposed surgically for placement of a perineural catheter to permit delivery of 1 mL of 2% mepivacaine hydrochloride. Six hours after recovery from anesthesia, each horse was videotaped while walking (50-step data acquisition period) before and after administration of mepivacaine. Videotapes were reviewed and the proportion of abnormal steps before and after selective SSN anesthesia was assessed. A step was considered abnormal if a marked amount of scapulohumeral joint instability (ie, lateral luxation of the proximal portion of the humerus) was observed during the weight-bearing phase of the stride. Results-Clinically apparent gait dysfunction was detected in all 3 horses following perineural administration of the local anesthetic agent. Anesthesia of the SSN resulted in scapulohumeral joint instability as evidenced by consistent lateral excursion of the shoulder region during the weight-bearing phase of gait at a walk. The proportion of abnormal steps before and after SSN anesthesia was significantly different in all 3 horses. Conclusions and Clinical Relevance-These data support the role of the SSN in shoulder joint stability in horses and define SSN dysfunction as 1 mechanism by which the syndrome and gait dysfunction clinically referred to as sweeny may develop.

Objective-To assess the biological response to recombinant feline interferon-omega (rFeIFN-omega) following ocular or oral administration in cats via estimation of Mx protein expression in conjunctival cells (CCs) and WBCs. Animals-10 specific pathogen-free cats. Procedures-In multiple single-dose drug experiments, each cat received various concentrations of rFeIFN-omega administered topically into both eyes (50 to 10,000 U/eye) and orally (200 to 20,000 units). The same cats received saline (0.9% NaCl) solution topically and orally as control treatments. The CCs and WBCs were collected prior to treatment (day 0), on day 1, and every third or seventh day thereafter until samples yielded negative results for Mx protein. Samples were examined for Mx protein expression via immunohistochemistry and immunoblotting procedures involving murine anti-Mx protein monoclonal antibody M143. Results-After topical application of 10,000 U of rFeIFN-omega/eye, CCs stained for Mx protein for a minimum of 7 days, whereas WBCs were positive for Mx protein for a minimum of 31 days. After topical application of lower concentrations, CCs did not express Mx protein, in contrast to WBCs, which stained for Mx protein at 1,000 units for at least 1 day. Following oral administration, Mx protein was expressed in WBCs at rFeIFN-omega concentrations as low as 200 units, whereas CCs did not stain for Mx protein at any concentration. Conclusions and Clinical Relevance-Results indicate that Mx protein expression (a marker of the biological response to rFeIFN-omega) in CCs and WBCs of rFeIFN-omega-treated cats depends on the dose of rFeIFN-omega, site of administration, and cell type.

Objective-To evaluate the efficacy and safety of intra-articular administration of ethyl alcohol for arthrodesis of tarsometatarsal joints in horses. Animals-8 healthy female horses without lameness or radiographic evidence of tarsal joint osteoarthritis. Procedure-In each horse, 1 tarsometatarsal joint was treated with 4 mL of 70% ethyl alcohol and the opposite joint was treated with 4 mL of 95% ethyl alcohol. Lameness examinations were performed daily for 2 weeks, followed by monthly evaluations for the duration of the 12-month study. Radiographic evaluations of both tarsi were performed 1 month after injection and every 3 months thereafter. Gross and histologic examinations of the tarsi were undertaken at completion of the study. Results-Horses had minimal to no lameness associated with the treatments. Radiography revealed that 8 of 16 joints were fused by 4 months after treatment, with significantly more joints fused in the 70% ethyl alcohol group. Fifteen of 16 joints were considered fused at postmortem examination at 12 months. Gross and histologic examinations revealed foci of dense mature osteonal bone spanning the joint spaces. Bony fusion appeared to be concentrated on the dorsolateral, centrolateral, and plantarolateral aspects of the joints. Significant differences were not detected between treatment groups for lameness or pathologic findings. Conclusions and Clinical Relevance-Administration of ethyl alcohol into the tarsometatarsal joint of healthy horses appeared to facilitate arthrodesis of the joint in a pain-free manner. Results warrant further investigation into the potential use of ethyl alcohol in horses clinically affected with osteoarthritis of the tarsometatarsal and distal intertarsal joints.

Objective-To evaluate the effect of dietary supplementation with the probiotic strain Lactobacillus acidophilus DSM13241 in healthy adult cats. Animals-15 adult cats. Procedures-Cats were fed a nutritionally complete dry food for 5 weeks. Fecal character was assessed daily, and a single fecal sample and 3-mL blood sample were collected for bacterial enumeration and hematologic analysis, respectively. Cats were then fed the same diet supplemented with L acidophilus DSM13241 (2 X 10(8) CFU/d) for 4.5 weeks. Repeat fecal and hematologic measurements were taken prior to the return to control diet for a 4-week period. Results-The probiotic species was recovered from feces, demonstrating survival through the feline gastrointestinal tract. Probiotic supplementation was associated with increased numbers of beneficial Lactobacillus and L acidophilus groups in feces and decreased numbers of Clostridium spp and Enterococcus faecalis, indicating an altered bacterial balance in the gastrointestinal tract microflora. Fecal pH was also decreased suggesting a colonic environment selective for the beneficial lactic acid bacterial population. Systemic and immunomodulatory effects were associated with administration of L acidophilus DSM13241 including altered cell numbers within WBC subsets and enhanced phagocytic capacity in the peripheral granulocyte population. In addition, plasma endotoxin concentrations were decreased during probiotic feeding, and RBCs had a decreased susceptibility to osmotic pressure. Conclusions and Clinical Relevance-Probiotic strain L acidophilus DSM13241 fed at 2 X 10(8) CFU/d can alter the balance of gastrointestinal microflora in healthy cats. Furthermore, administration of this probiotic results in beneficial systemic and immunomodulatory effects in cats.

Objective-To investigate the effects of IV administration of ergotamine and ergovaline and intraruminal administration of ergotamine on electromyographic (EMG) activity of reticuloruminal smooth muscle in conscious sheep. Animals-3 sheep with indwelling electrodes in the musculature of the reticulum and rumen. Procedure-In a crossover design study, reticuloruminal motility before and after IV administration of ergotamine (5, 10, 20, and 40 nmol/kg) or ergovaline (2.5, 5, and 10 nmol/kg) was evaluated; EMG effects were compared with those of corresponding control treatments (IV administration of saline 0.9% NaCl solution or acetone, respectively) in sheep. Ergotamine (800 nmol/kg) or water was also administered intraruminally and their effects compared. Results-After IV administration of ergopeptides, vagally dependent cyclical A and B sequences of contraction of the reticulorumen were immediately inhibited, preceding increases in baseline EMG activity (tonus). The return of cyclical contractions was associated with an increase in contraction amplitude. The effects were dose dependent; administration of 40 nmol of ergotamine/kg resulted in responses that continued for 3 to 4 hours. The effects of intraruminal administration of ergotamine were variable; after 8 hours, EMG activity was increased from baseline for < 2 hours in 1 sheep, 10 hours in another, and > 15 hours in the third. Conclusions and Clinical Relevance-In sheep, the effects of ergotamine and ergovaline on reticuloruminal motility after IV administration and the duration of responses following intraruminal administration suggest that disruption of digestion may occur in animals grazing endophyte-infected pasture that has a high ergopeptide content.

Objective-To evaluate the effects of deracoxib and aspirin on serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) in healthy dogs. Animals-24 dogs. Procedure-Dogs were allocated to 1 of 3 groups of 8 dogs each. Dogs received the vehicle used for deracoxib tablets (PO, q 8 h; placebo), aspirin (23 to 25 mg/kg, PO, q 8 h), or deracoxib (1.25 to 1.8 mg/kg, PO, q 24 h) and placebo (PO, q 8 h) for 28 days. Measurement of serum concentrations of T4, T3, fT4, and TSH were performed 7 days before treatment (day -7), on days 14 and 28 of treatment, and 14 days after treatment was discontinued. Plasma total protein, albumin, and globulin concentrations were measured on days -7 and 28. Results-Mean serum T4, fT4, and T3 concentrations decreased significantly from baseline on days 14 and 28 of treatment in dogs receiving aspirin, compared with those receiving placebo. Mean plasma total protein, albumin, and globulin concentrations on day 28 decreased significantly in dogs receiving aspirin, compared with those receiving placebo. Fourteen days after administration of aspirin was stopped, differences in hormone concentrations were no longer significant. Differences in serum TSH or the free fraction of T4 were not detected at any time. No significant difference in any of the analytes was detected at any time in dogs treated with deracoxib. Conclusions and Clinical Relevance-Aspirin had substantial suppressive effects on thyroid hormone concentrations in dogs. Treatment with high dosages of aspirin, but not deracoxib, should be discontinued prior to evaluation of thyroid function.

Objective-To investigate effects of isoflurane at approximately the minimum alveolar concentration (MAC) on the nociceptive withdrawal reflex (NWR) of the forelimb of ponies as a method for quantifying anesthetic potency. Animals-7 healthy adult Shetland ponies. Procedure-Individual MAC (iMAC) for isoflurane was determined for each pony. Then, effects of isoflurane administered at 0.85, 0.95, and 1.05 iMAC on the NWR were assessed. At each concentration, the NWR threshold was defined electromyographically for the common digital extensor and deltoid muscles by stimulating the digital nerve; additional electrical stimulations (3, 5, 10, 20, 30, and 40 mA) were delivered, and the evoked activity was recorded and analyzed. After the end of anesthesia, the NWR threshold was assessed in standing ponies. Results-Mean +/- SD MAC of isoflurane was 1.0 +/- 0.2%. The NWR thresholds for both muscles increased significantly in a concentration-dependent manner during anesthesia, whereas they decreased in awake ponies. Significantly higher thresholds were found for the deltoid muscle, compared with thresholds for the common digital extensor muscle, in anesthetized ponies. At each iMAC tested, amplitudes of the reflex responses from both muscles increased as stimulus intensities increased from 3 to 40 mA. A concentration-dependent depression of evoked reflexes with reduction in slopes of the stimulus-response functions was detected. Conclusions and Clinical Relevance-Anesthetic-induced changes in sensory-motor processing in ponies anesthetized with isoflurane at concentrations of approximately 1.0 MAC can be detected by assessment of NWR. This method will permit comparison of effects of inhaled anesthetics or anesthetic combinations on spinal processing in equids.

Objective-To evaluate various sampling strategies for potential use in measuring prevalence of antimicrobial susceptibility in cattle. Sample Population-500 isolates of non-type-specific Escherichia coli (NTSEC) isolated from the feces of 50 cows from 2 dairy farms (25 cows/farm and 10 isolates/cow). Procedures-Diameters of inhibition zones for 12 antimicrobials were analyzed to estimate variation among isolates, cows, and farms and then used to determine sampling distributions for a stochastic simulation model to evaluate 4 sampling strategies. These theoretic sampling strategies used a total of 100 isolates in 4 allocations (1 isolate from 100 cows, 2 isolates from 50 cows, 3 isolates from 33 cows, or 4 isolates from 25 cows). Results-Analysis of variance composition revealed that 74.2% of variation was attributable to isolates, 18.5% to cows, and 7.3% to farms. Analysis of results of simulations suggested that when most of the variance was attributable to differences among isolates within a cow, culturing 1 isolate from each of 100 cows underestimated overall prevalence, compared with results for culturing more isolates per cow from fewer cows. When variance was not primarily attributable to differences among isolates, all 4 sampling strategies yielded similar results. Conclusions and Clinical Relevance-It is not always possible to predict the hierarchical level at which clustering will have its greatest impact on observed susceptibility distributions. Results suggested that sampling strategies that use testing of 3 or 4 isolates/cow from a representative sample of all animals better characterize herd prevalence of antimicrobial resistance when impacted by clustering.