OBJECTIVE To evaluate the plasma disposition of mycophenolic acid (MPA) and its derivatives MPA glucuronide and MPA glucoside after twice-daily infusions of mycophenolate mofetil (MMF) in healthy cats for 3 days and to assess the effect of MMF administration on peripheral blood mononuclear cell (PBMC) counts and CD4+-to-CD8+ ratios. ANIMALS 5 healthy adult cats. PROCEDURES MMF was administered to each cat (10 mg/kg, IV, q 12 h for 3 days). Each dose of MMF was diluted with 5% dextrose in water and then administered over a 2-hour period with a syringe pump. Blood samples were collected for analysis. A chromatographic method was used to quantitate concentrations of MPA and its metabolites. Effects of MMF on PBMC counts and CD4+-to-CD8+ ratios were assessed by use of flow cytometry. RESULTS All cats biotransformed MMF into MPA. The MPA area under the plasma concentration–time curve from 0 to 14 hours ranged from 14.6 to 37.6 mg·h/L and from 14.4 to 22.3 mg·h/L after the first and last infusion, respectively. Total number of PBMCs was reduced in 4 of 5 cats (mean ± SD reduction, 25.9 ± 15.8% and 26.7 ± 19.3%) at 24 and 48 hours after the end of the first infusion of MMF, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Plasma disposition of MPA after twice-daily IV infusions for 3 days was variable in all cats. There were no remarkable changes in PBMC counts and CD4+-to-CD8+ ratios.

OBJECTIVE To compare dialysate sodium concentration and patient plasma sodium concentration of dogs during intermittent hemodialysis treatments. SAMPLE 211 intermittent hemodialysis treatments performed on 40 client-owned dogs for the management of dialysis-dependent uremia. PROCEDURES Medical records were reviewed to determine the plasma sodium concentration of each dog before and after routine hemodialysis treatments. Associations between detected changes in plasma sodium concentration and dialysate sodium concentration were evaluated by use of Spearman rank correlations and linear regression analysis. RESULTS Significant linear correlations were found between the dialysate sodium concentration and patient sodium concentration. The starting dialysate-to-patient sodium gradient was associated with the strongest correlation to the change in patient sodium concentration at the end of the dialysis session. Modest correlations existed between the dialysate sodium concentration and postdialysis patient sodium concentration as well as between the predialysis dialysate-to-patient sodium gradient and postdialysis dialysate-to-patient sodium gradient. CONCLUSIONS AND CLINICAL RELEVANCE The dialysate sodium concentration was correlated with the patient sodium concentration in dogs, and the dialysate-to-patient sodium gradient could be used to further refine this association to predict the postdialysis patient sodium concentration and potentially manage dysnatremia during hemodialysis. Prospective studies should be performed to determine how these associations can be used to correct aberrations as well as to avoid unwanted alterations in patient sodium concentrations.

The objective of this study was to compare clinical, microbiologic, immunologic, and pathologic parameters in pigs each concurrently administered porcine reproductive and respiratory syndrome virus (PRRSV), Mycoplasma hyopneumoniae, and porcine circovirus type 2 (PCV2) vaccine from 1 of 2 commercial sources at 21 days of age and challenged with field strains of each of the 3 pathogens. Pigs were challenged with PRRSV and M. hyopneumoniae at 42 days of age (-14 days post-challenge, dpc) followed by a challenge with PCV2 at 56 days of age (0 dpc). Significant differences were observed between vaccinated challenged and unvaccinated challenged groups in clinical (average daily gain and clinical signs), microbiologic (viremia and nasal shedding), immunologic (antibodies and interferon-γ secreting cells), and pathologic (lesions) outcomes. Significant differences were observed among the 3 vaccinated challenged groups in microbiologic (nasal shedding of M. hyopneumoniae and viremia of PCV2) and immunologic (M. hyopneumoniae- and PCV2-specific interferon-γ secreting cells) outcomes. The vaccination regimen for PRRSV vaccine, M. hyopneumoniae vaccine, and PCV2 vaccine is efficacious for controlling triple challenge with PRRSV, M. hyopneumoniae, and PCV2 from weaning to finishing period.

OBJECTIVE To evaluate the efficacy of each of 3 incremental doses of MK-467 for alleviation of dexmedetomidine-induced hemodynamic depression in isoflurane-anesthetized cats. ANIMALS 6 healthy adult domestic shorthair cats. PROCEDURES Each cat was anesthetized with isoflurane and received a target-controlled infusion of dexmedetomidine estimated to maintain the plasma dexmedetomidine concentration at 10 ng/mL throughout the experiment. Heart rate (HR) and direct arterial pressures were measured at baseline (isoflurane administration only), during dexmedetomidine infusion, and before and after IV administration of each of 3 serially increasing doses (15, 30, and 60 μg/kg) of MK-467. Cardiac index (CI) and systemic vascular resistance (SVR) were recorded at baseline, during dexmedetomidine infusion, and at the mean arterial pressure nadir after administration of the 30- and 60-μg/kg doses of MK-467. RESULTS Compared with baseline values, the dexmedetomidine infusion significantly decreased HR and increased arterial pressures. Each dose of MK-467 caused a significant decrease in arterial pressures and a significant, albeit clinically irrelevant, increase in HR (≤ 10%). Following administration of the 30- and 60-μg/kg doses of MK-467, all cats developed clinical hypotension (mean arterial pressure, < 60 mm Hg) even though CI and SVR returned to baseline values. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated administration of small doses of MK-467 to isoflurane-anesthetized cats receiving dexmedetomidine restored CI and SVR, but caused a substantial decrease in arterial pressures and only a marginal increase in HR. Therefore, caution should be used when MK-467 is administered to alleviate dexmedetomidine-induced hemodynamic depression in isoflurane-anesthetized cats.

OBJECTIVE To evaluate effects of 2 levels of partial neuromuscular block on the ventilatory response to a hypercapnic challenge in anesthetized dogs and to evaluate effects of edrophonium for reversing partial neuromuscular block. ANIMALS 6 healthy adult Beagles. PROCEDURES Each dog was anesthetized twice with propofol and dexmedetomidine. End-tidal partial pressure of CO2 (P(etco2)), tidal volume (V(t)), and peak inspiratory flow (PIF) were measured during breathing at rest. Maximal V(t) and PIF (V(tMAX) and PIF(MAX), respectively) in response to a hypercapnic challenge consisting of 10% CO2 inhaled for 1 minute were measured. Variables were measured before administration of atracurium (baseline), during moderate (train-of-four [TOF] ratio, 0.3 to 0.5) and mild (TOF ratio, 0.6 to 0.8) atracurium-induced neuromuscular block, and after neuromuscular block recovery (TOF ratio, ≥ 0.9) following administration of edrophonium or saline (0.9% NaCl) solution. Dogs for which any variable returned to < 80% of the baseline value were identified. RESULTS Partial neuromuscular block increased P(etco2); it impaired V(t) at rest and Vt(MAX) but not PIF at rest and PIF(MAX). All variables except P(etco2) returned to baseline values when the TOF returned to ≥ 0.9. After recovery from neuromuscular block, significantly more dogs had a V(tMAX) < 80% of the baseline value when edrophonium was not administered. CONCLUSIONS AND CLINICAL RELEVANCE Partial neuromuscular block in anesthetized Beagles decreased spontaneous ventilation at rest and impaired the response to a hypercapnic challenge. Response to hypercapnic challenge might remain partially impaired after recovery of the TOF ratio to ≥ 0.9.

OBJECTIVE To assess pharmacokinetics of tranexamic acid (TXA) in dogs and assess antifibrinolytic properties of TXA in canine blood by use of a thromboelastography-based in vitro model of hyperfibrinolysis. ANIMALS 6 healthy adult dogs. PROCEDURES Dogs received each of 4 TXA treatments (10 mg/kg, IV; 20 mg/kg, IV; approx 15 mg/kg, PO; and approx 20 mg/kg, PO) in a randomized crossover-design study. Blood samples were collected at baseline (time 0; immediately prior to drug administration) and predetermined time points afterward for pharmacokinetic analysis and pharmacodynamic (thromboelastography) analysis by use of an in vitro hyperfibrinolysis model. RESULTS Maximum amplitude (MA [representing maximum clot strength]) significantly increased from baseline at all time points for all treatments. The MA was lower at 360 minutes for the 10-mg/kg IV treatment than for other treatments. Percentage of clot lysis 30 minutes after MA was detected was significantly decreased from baseline at all time points for all treatments; at 360 minutes, this value was higher for the 10-mg/kg IV treatment than for other treatments and higher for the 20-mg/kg IV treatment than for the 20-mg/kg PO treatment. Maximum plasma TXA concentrations were dose dependent. At 20 mg/kg, IV, plasma TXA concentrations briefly exceeded concentrations suggested for complete inhibition of fibrinolysis. Oral drug administration resulted in a later peak antifibrinolytic effect than did IV administration. CONCLUSIONS AND CLINICAL RELEVANCE Administration of TXA improved clot strength and decreased fibrinolysis in blood samples from healthy dogs in an in vitro hyperfibrinolysis model. Further research is needed to determine clinical effects of TXA in dogs with hyperfibrinolysis.

OBJECTIVE To determine effects for 2 IV regional limb perfusion (IVRLP) protocols involving tiludronate on lameness of horses with navicular syndrome. ANIMALS 15 horses with bilateral forelimb navicular syndrome. PROCEDURES Shoeing and anti-inflammatory injection into the distal interphalangeal joint (DIPJ) of both forelimbs (day 0) were performed on all horses. On day 14, horses received 1 of 3 IVRLPs consisting of 0.1 mg of tiludronate/kg (low-dose tiludronate [LDT]; n = 5), 0.2 mg of tiludronate/kg (high-dose tiludronate [HDT]; 5), or saline (0.9% NaCl) solution (placebo; 5); treatments were repeated at days 24 and 34. Lameness severity of both forelimbs was evaluated via subjective evaluation and force plate analysis before and after shoeing on day 0 and at days 14, 34, 60, and 120. Mean subjective lameness score and peak vertical ground reaction force (PVGRF) for the more severely lame forelimb (LFL) and both (combined) forelimbs (CFL) were compared over time. RESULTS For all horses, mean PVGRF for the LFL and CFL was increased at 14 days. No difference in mean subjective lameness score or mean PVGRF was detected within groups at any time. Mean PVGRF of the CFL was higher for the HDT group than the LDT and placebo groups only at 120 days. CONCLUSIONS AND CLINICAL RELEVANCE Use of the tiludronate IVRLP protocols described here provided no further improvement in lameness over therapeutic shoeing and anti-inflammatory injection of the DIPJ in horses with navicular syndrome. However, HDT-treated horses were objectively less lame than LDT- or placebo-treated horses at 120 days.

OBJECTIVE To evaluate the effect of a bovine albumin–derivatized glutaraldehyde (BA-DG) biopolymer sealant on leakage pressures of intestinal anastomoses in jejunal tissue collected from fresh canine cadavers and to evaluate changes in circumference and cross-sectional area of the anastomotic site resulting from sealant application. SAMPLE 24 jejunal anastomoses from 4 fresh canine cadavers. PROCEDURES Jejunal tissue specimens were collected, and adjacent segment anastomoses were created within 12 hours after euthanasia of each dog. The tissue constructs were randomly assigned to 1 of 2 groups in which sealant was or was not applied. The outer circumference of all anastomoses in the sealant group was measured before and after application of the sealant; the cross-sectional area at the anastomotic site was then calculated at each time point. Tissue constructs were pressure tested, and leakage pressure and site were recorded. All testing was completed within 24 hours after tissue collection. RESULTS Compared with preapplication findings, there were no significant changes in outer circumference or cross-sectional area at the anastomotic site after sealant application. Leakage pressures in the sealant group were significantly higher than those in the no-sealant group. CONCLUSIONS AND CLINICAL RELEVANCE The use of surgical sealant on fresh canine cadaver jejunal anastomoses resulted in significantly higher leakage pressure at the anastomotic site; no immediate tissue deformation of the outer circumference or cross-sectional area occurred after sealant application. Future in vivo investigations are warranted to evaluate the effects of this sealant and potential benefits for clinical patients undergoing enterectomy.

OBJECTIVE To evaluate the thermal antinociceptive effects and pharmacokinetics of hydromorphone hydrochloride after IM administration to cockatiels (Nymphicus hollandicus). ANIMALS 16 healthy adult cockatiels. PROCEDURES During the first of 2 study phases, each cockatiel received each of 4 treatments (hydromorphone at doses of 0.1, 0.3, and 0.6 mg/kg and saline [0.9% NaCl] solution [0.33 mL/kg; control], IM), with a 14-day interval between treatments. For each bird, foot withdrawal to a thermal stimulus was determined following assignment of an agitation-sedation score at predetermined times before and for 6 hours after each treatment. During the second phase, a subset of 12 birds received hydromorphone (0.6 mg/kg, IM), and blood samples were collected at predetermined times for 9 hours after drug administration. Plasma hydromorphone concentration was determined by liquid chromatography–mass spectrometry. Noncompartmental analysis of sparse data was used to calculate pharmacokinetic parameters. RESULTS Thermal withdrawal response did not differ among the 4 treatment groups at any time. Agitation-sedation scores following administration of the 0.3-and 0.6-mg/kg doses of hydromorphone differed significantly from those treated with saline solution and suggested the drug had a sedative effect. Plasma hydromorphone concentrations were > 1 ng/mL for 3 to 6 hours after drug administration in all birds. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that IM administration of hydromorphone at the evaluated doses did not increase the thermal withdrawal threshold of cockatiels despite plasma drug concentrations considered therapeutic for other species. Further research is necessary to evaluate the analgesic effects of hydromorphone in cockatiels.

OBJECTIVE To characterize delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) features of healthy hyaline cartilage of the distal interphalangeal joint (DIPJ) of horses, to determine whether dGEMRIC can be used to differentiate various stages of naturally occurring osteoarthritis of the DIPJ, and to correlate relaxation times determined by dGEMRIC with the glycosaminoglycan concentration, water content, and macroscopic and histologic findings of hyaline cartilage of DIPJs with and without osteoarthritis. SAMPLE 1 cadaveric forelimb DIPJ from each of 12 adult warmblood horses. PROCEDURES T1-weighted cartilage relaxation times were obtained for predetermined sites of the DIPJ before (T1preGd) and after (T1postGd) intra-articular gadolinium administration. Corresponding cartilage sites underwent macroscopic, histologic, and immunohistochemical evaluation, and cartilage glycosaminoglycan concentration and water content were determined. Median T1preGd and T1postGd were correlated with macroscopic, histologic, and biochemical data. Mixed generalized linear models were created to evaluate the effects of cartilage site, articular surface, and macroscopic and histologic scores on relaxation times. RESULTS 122 cartilage specimens were analyzed. Median T1postGd was lower than the median T1preGd for normal and diseased cartilage. Both T1preGd and T1postGd were correlated with macroscopic and histologic scores, whereby T1preGd increased and T1postGd decreased as osteoarthritis progressed. There was topographic variation of T1preGd and T1postGd within the DIPJ. Cartilage glycosaminoglycan concentration and water content were significantly correlated with T1preGd and macroscopic and histologic scores but were not correlated with T1postGd. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that dGEMRIC relaxation times varied for DIPJs with various degrees of osteoarthritis. These findings may help facilitate early detection of osteoarthritis.