Objective-To investigate the mechanisms by which corticosteroid administration may predispose cats to congestive heart failure (CHF). Animals-12 cats receiving methylprednisolone acetate (MPA) for the treatment of dermatologic disorders. Procedure-The study was conducted as a repeated-measures design. Various baseline variables were measured, after which MPA (5 mg/kg, IM) was administered. The same variables were then measured at 3 to 6 days and at 16 to 24 days after MPA administration. Evaluations included physical examination, systolic blood pressure measurement, hematologic analysis, serum biochemical analysis, thoracic radiography, echocardiography, and total body water and plasma volume determination. Results-MPA resulted in a substantial increase in serum glucose concentration at 3 to 6 days after administration. Concurrently, RBC count, Hct, and hemoglobin concentration as well as serum concentrations of the major extracellular electrolytes, sodium and chloride, decreased. Plasma volume increased by 13.4% (> 40% in 3 cats), whereas total body water and body weight slightly decreased. All variables returned to baseline by 16 to 24 days after MPA administration. Conclusions and Clinical Relevance-These data suggest that MPA administration in cats causes plasma volume expansion as a result of an intra- to extracellular fluid shift secondary to glucocorticoid-mediated extracellular hyperglycemia. This mechanism is analogous to the plasma volume expansion that accompanies uncontrolled diabetes mellitus in humans. Any cardiovascular disorders that impair the normal compensatory mechanisms for increased plasma volume may predispose cats to CHF following MPA administration.

Objective-To biomechanically and histologically compare single-layer continuous Cushing and simple continuous appositional cystotomy closure in rats with xylene-induced cystitis. Animals-40 female Sprague-Dawley rats. Procedure-Rats were anesthetized, their urinary bladders catheterized and evacuated, and xylene instilled in each bladder for 5 minutes and then aspirated. Forty-eight hours later, ventral midline celiotomy and cystotomy (8 mm) were performed. Cystotomies were closed with 6-0 poliglecaprone 25 by use of a single-layer continuous Cushing or simple continuous appositional pattern (20 rats/group), and cystotomy times were recorded. Rats were allocated to healing durations (5 rats/group) of 0, 3, 7, and 14 days. Celiotomies were closed in a routine manner. After the allotted healing interval, another celiotomy was performed, the urethra cannulated, and ureters ligated. The cannula was secured to the urethra, and the bladder infused at 0.1 mL/min. Leak pressure volume, leak pressure, peak pressure volume, and peak pressure were recorded via a pressure transducer. Bladders were harvested and histologically assessed. Results-Cystotomy time, biomechanical testing values, and overall inflammation scores did not differ between closure methods for any healing duration. Both methods had significantly greater leak pressures, with the appositional method also having significantly greater peak pressures on day 7, compared to day 0. Biomechanical testing values decreased from day 7 to 14 as a result of juxtaincisional weakening of the bladder and xylene-induced changes in collagen. Conclusions and Clinical Relevance-Simple continuous appositional was equal biomechanically and histologically to continuous Cushing for all comparison variables. Poliglecaprone 25 was acceptable for cystotomy closure.

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 determine the pharmacokinetics of marbofloxacin after single IV and orally administered doses in blue and gold macaws. Animals-10 healthy blue and gold macaws. Procedures-In a crossover study, marbofloxacin (2.5 mg/kg) was administered orally (via crop gavage) to 5 birds and IV to 5 birds. Blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hours after marbofloxacin administration. After a 4-week washout period, the study was repeated, with the first 5 birds receiving the dose IV and the second 5 birds receiving the dose orally. Serum marbofloxacin concentrations were quantitated by use of a validated liquid chromatography-mass spectrometry assay. Results-After oral administration, mean +/- SD area under the curve was 7.94 +/- 2.08 microgram.h/mL, maximum plasma concentration was 1.08 +/- 0.316 microgram/mL, and bioavailability was 90.0 +/- 31%. After IV administration of marbofloxacin, the apparent volume of distribution was 1.3 +/- 0.32 L/kg, plasma clearance was 0.29 +/- 0.078 L/h/kg, area under the curve was 9.41 +/- 2.84 microgram.h/mL, and the harmonic mean terminal half-life was 4.3 hours. Conclusions and Clinical Relevance-Single IV and orally administered doses of marbofloxacin were well tolerated by blue and gold macaws. The orally administered dose was well absorbed. Administration of marbofloxacin at a dosage of 2.5 mg/kg, PO, every 24 hours may be appropriate to control bacterial infections susceptible to marbofloxacin in this species.

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.

Objectives-To measure serum polymyxin B concentration after single and repeated IV infusions in horses. Animals-5 healthy horses. Procedures-In study 1, 1 mg (6,000 U) of polymyxin B/kg was given IV and blood samples were collected for 24 hours. In study 2, 1 mg of polymyxin B/kg was given IV every 8 hours for 5 treatments and blood samples were collected until 24 hours after the last dose. Polymyxin B concentration was measured as the ability to suppress nitrite production by murine macrophages stimulated with lipopolysaccharide and interferon-alpha. Urine was collected prior to the first drug infusion and 24 hours after the fifth drug infusion for determination of urinary gamma-glutamyl transferase (GGT)-to-creatinine ratios. Results-In study 1, mean +/- SEM maximal serum polymyxin B concentration was 2.93 +/- 0.38 microgram/mL. Polymyxin B was undetectable 18 hours after infusion. In study 2, maximal polymyxin B concentrations after the first and fifth doses were 2.98 +/- 0.81 microgram/mL and 1.91 +/- 0.50 microgram/mL, respectively. Mean trough concentration for all doses was 0.22 +/- 0.01 microgram/mL. A significant effect of repeated administration on peak and trough serum concentration was not detected. Urine GGT-to-creatinine ratios were not affected by polymyxin B administration. Conclusions and Clinical Relevance-Polymyxin B given as multiple infusions to healthy horses by use of this protocol did not accumulate in the vascular compartment and appeared safe. Results support repeated IV use of 1 mg of polymyxin B/kg at 8-hour intervals as treatment for endotoxemia.