OBJECTIVE To investigate use of the plethysmographic variability index (PVI) and perfusion index (PI) for evaluating changes in arterial blood pressure in anesthetized tigers (Panthera tigris). ANIMALS 8 adult tigers. PROCEDURES Each tiger was anesthetized once with a combination of ketamine, midazolam, medetomidine, and isoflurane. Anesthetic monitoring included assessment of PI, PVI, direct blood pressure measurements, anesthetic gas concentrations, esophageal temperature, and results of capnography and ECG. Mean arterial blood pressure (MAP) was maintained for at least 20 minutes at each of the following blood pressure conditions: hypotensive (MAP = 50 ± 5 mm Hg), normotensive (MAP = 70 ± 5 mm Hg), and hypertensive (MAP = 90 ± 5 mm Hg). Arterial blood gas analysis was performed at the beginning of anesthesia and at each blood pressure condition. RESULTS Mean ± SD PI values were 1.82 ± 2.38%, 1.17 ± 0.77%, and 1.71 ± 1.51% and mean PVI values were 16.00 ± 5.07%, 10.44 ± 3.55%, and 8.17 ± 3.49% for hypotensive, normotensive, and hypertensive conditions, respectively. The PI values did not differ significantly among blood pressure conditions. The PVI value for the hypotensive condition differed significantly from values for the normotensive and hypertensive conditions. The PVI values were significantly correlated with MAP (r = −0.657). The OR of hypotension to nonhypotension for PVI values ≥ 18% was 43.6. CONCLUSIONS AND CLINICAL RELEVANCE PVI was a clinically applicable variable determined by use of noninvasive methods in anesthetized tigers. Values of PVI ≥ 18% may indicate hypotension.

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 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 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.

OBJECTIVE To determine plasma concentrations of lidocaine after laryngeal administration or laryngeal and intratesticular administration in cats. ANIMALS 14 healthy adult sexually intact male cats (7 cats/treatment). PROCEDURES Cats were randomly allocated to receive 0.1 mL of 2% or 10% lidocaine hydrochloride solution (treatments L2 and L10, respectively) sprayed on the larynx for laryngeal desensitization, followed by endotracheal intubation and isoflurane anesthesia. After a 7-day washout period, cats were again randomly allocated to receive treatment L2 or L10, and castration was performed under isoflurane anesthesia following intratesticular administration of 2% lidocaine solution (0.1 mL/kg). In both experiments, a blood sample for measurement of plasma lidocaine concentration was obtained before (0 minutes) and 3, 5, 10, 15, 20, 30, 45, 60, and 75 minutes after laryngeal administration of lidocaine solution. Anesthesia was discontinued at 60 minutes. Plasma lidocaine concentrations were measured with high-performance liquid chromatography. RESULTS After treatments L2 and L10, median maximum plasma lidocaine concentrations were 34.1 ng/mL (range, 0 to 279.4 ng/mL) and 93.6 ng/mL (range, 79.3 to 182.2 ng/mL), respectively. Time to maximum plasma concentration was 10 minutes (range, 0 to 20 minutes) for each treatment. When cats received intratesticular lidocaine administration following L2 or L10 treatment, median maximum plasma concentration was 181.0 ng/mL (range, 103.7 to 600.2 ng/mL) and 301.2 ng/mL (range, 265.8 to 1,770.0 ng/mL), respectively. CONCLUSIONS AND CLINICAL RELEVANCE On the basis of these data, combined laryngeal and intratesticular administration of lidocaine solution at a total dose of approximately 5 mg/kg appears to be safe for use in healthy adult cats.

OBJECTIVE To compare the pharmacokinetics of 2 commercial florfenicol formulations following IM and SC administration to sheep. ANIMALS 16 healthy adult mixed-breed sheep. PROCEDURES In a crossover study, sheep were randomly assigned to receive florfenicol formulation A or B at a single dose of 20 mg/kg, IM, or 40 mg/kg, SC. After a 2-week washout period, each sheep was administered the opposite formulation at the same dose and administration route as the initial formulation. Blood samples were collected immediately before and at predetermined times for 24 hours after each florfenicol administration. Plasma florfenicol concentrations were determined by high-performance liquid chromatography. Pharmacokinetic parameters were estimated by noncompartmental methods and compared between the 2 formulations at each dose and route of administration. RESULTS Median maximum plasma concentration, elimination half-life, and area under the concentration-time curve from time 0 to the last quantifiable measurement for florfenicol were 3.76 μg/mL, 13.44 hours, and 24.88 μg•h/mL, respectively, for formulation A and 7.72 μg/mL, 5.98 hours, and 41.53 μg•h/mL, respectively, for formulation B following administration of 20 mg of florfenicol/kg, IM, and 2.63 μg/mL, 12.48 hours, and 31.63 μg•h/mL, respectively, for formulation A and 4.70 μg/mL, 16.60 hours, and 48.32 μg•h/mL, respectively, for formulation B following administration of 40 mg of florfenicol/kg, SC. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that both formulations achieved plasma florfenicol concentrations expected to be therapeutic for respiratory tract disease caused by Mannheimia haemolytica or Pasteurella spp at both doses and administration routes evaluated.

As little information is available on the reproductive system of guinea fowl (Numida meleagris), a study was conducted on 49 male guinea fowl to document the histological structure and developmental changes in the luminal diameter of the ducts within the excurrent duct system and associated changes in concentrations of testosterone. Age-related changes were analyzed using the Kruskal-Wallis test and medians separated by the Mann-Whitney U-test. Tubuli recti were clearly visible in the guinea fowl and the rete testes were both intracapsular and extracapsular. Regardless of age, the luminal diameter of the proximal ductuli efferentes was the largest, while that of the connecting duct was the smallest. The luminal diameter of all ducts within the epididymal region increased (P < 0.001) monthly until 20 wk of age, and then increased marginally every month thereafter. Peripheral testosterone concentrations also peaked at 20 wk of age and declined thereafter. In adult birds, the ductus deferens enlarged posteriorly, from an average of about 279 μm cranially to 678 μm caudally. Peripheral testosterone concentrations strongly and positively correlated with the luminal diameter of ducts within the excurrent duct system. The pattern of increase in the luminal diameter of all ducts followed the pattern of testosterone secretion in these birds, which indicates that testosterone concentrations may be closely related to the development of the excurrent duct system in male guinea fowl.