OBJECTIVE To assess and compare results of anterior segment angiography of ophthalmologically normal cats following IV injection with indocyanine green and sodium fluorescein dyes. ANIMALS 10 client-owned cats. PROCEDURES Anterior segment angiography was performed in anesthetized cats following administration of 0.25% indocyanine green (1.0 mg/kg, IV) or 10% sodium fluorescein (20 mg/kg, IV) solution. All cats received both treatments. Imaging (1 eye/cat) was performed with a full-spectrum digital single-lens reflex camera equipped with an adaptor (1 image/s for 30 seconds) immediately following IV dye injection and 1, 2, 3, 4, and 5 minutes after injection. Onset and duration of arterial, capillary, and venous phases of iris vasculature were identified and compared statistically between treatments. Degree of iridal pigmentation, leakage of dye from iris vasculature, and image quality were subjectively assessed. RESULTS No differences were found in onset or duration of vascular phases between treatments. Visibility of the iris vasculature was not impaired by poor or moderate iridal pigmentation with either method. Indocyanine green provided subjectively better vascular detail and image contrast than sodium fluorescein. No vascular dye leakage was observed following indocyanine green administration. Leakage of dye from blood vessels in the stroma (in 10 cats) and presence of dye in the anterior chamber (in 5 cats) were detected after sodium fluorescein administration. CONCLUSIONS AND CLINICAL RELEVANCE Images obtained with either fluorescent dye were considered to be of diagnostic quality. Lack of leakage following indocyanine green administration suggested this treatment may have better diagnostic utility for anterior segment angiography. The photographic equipment used provided a cost-effective alternative to existing imaging systems.

OBJECTIVE To determine pharmacokinetic and pharmacodynamic properties of the novel factor Xa inhibitor apixaban in clinically normal cats. ANIMALS 5 purpose-bred domestic shorthair cats. PROCEDURES A single dose of apixaban (0.2 mg/kg, PO) was administered to each cat (time 0), and blood samples were obtained at 0, 15, 30, 45, 60, 120, 240, 360, 480, and 1,440 minutes. After a 1-week washout period, another dose of apixaban (0.2 mg/kg, IV) was administered to each cat, and blood samples were obtained at 0, 5, 10, 15, 30, 45, 60, 120, 240, 360, 480, and 1,440 minutes. Apixaban concentrations in plasma were measured via liquid chromatography–tandem mass spectrometry. Pharmacodynamic effects of apixaban were determined with a commercial assay for factor × activity, which measures endogenous factor Xa activity chromogenically. RESULTS Factor Xa was inhibited as a function of time after a single dose of apixaban administered orally or IV, and a direct inverse correlation with the plasma apixaban concentration was detected. Pharmacokinetic analysis revealed moderate clearance, short half-life, and high bioavailability for apixaban. A 2-compartment model was fit to the IV pharmacokinetic data; compartmental modeling could not be used to adequately describe the oral data because of substantial interindividual variability. CONCLUSIONS AND CLINICAL RELEVANCE Results inticated that apixaban was an effective inhibitor of factor Xa in cats. Further studies will be needed to determine pharmacokinetics and pharmacodynamics after multidose administration, effects of cardiac disease on pharmacokinetics and pharmacodynamics, dosing recommendations, and efficacy of apixaban for use in the treatment and prevention of thromboembolic disease in cats.

OBJECTIVE To determine the pharmacokinetics of pergolide after IV administration to horses. ANIMALS 8 healthy adult horses. PROCEDURES Pergolide mesylate was administered IV at a dose of 20 μg/kg (equivalent to 15.2 μg of pergolide/kg) to each horse, and blood samples were collected over 48 hours. Pergolide concentrations in plasma were determined by means of high-performance liquid chromatography–tandem mass spectrometry, and pharmacokinetic parameters were determined on the basis of noncompartmental methods. RESULTS After IV administration of pergolide, mean ± SD clearance, elimination half-life, and initial volume of distribution were 959 ± 492 mL/h/kg, 5.64 ± 2.36 hours, and 0.79 ± 0.32 L/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE With an elimination half-life of approximately 6 hours, twice-daily dosing may be more appropriate than once-daily dosing to reduce peak-trough fluctuation in pergolide concentrations. Further pharmacodynamic and pharmacokinetic studies of pergolide and its metabolites will be necessary to determine plasma concentrations that correlate with clinical effectiveness to determine the therapeutic range for the treatment of pituitary pars intermedia dysfunction.

OBJECTIVE To compare the attenuation of the angiotensin I–induced blood pressure response by once-daily oral administration of various doses of angiotensin receptor blockers (irbesartan, telmisartan, and losartan), benazepril hydrochloride, or lactose monohydrate (placebo) for 8 days in clinically normal cats. ANIMALS 6 healthy cats (approx 17 months old) with surgically implanted arterial telemetric blood pressure–measuring catheters. PROCEDURES Cats were administered orally the placebo or each of the drug treatments (benazepril [2.5 mg/cat], irbesartan [6 and 10 mg/kg], telmisartan [0.5, 1, and 3 mg/kg], and losartan [2.5 mg/kg]) once daily for 8 days in a crossover study. Approximately 90 minutes after capsule administration on day 8, each cat was anesthetized and arterial blood pressure measurements were recorded before and after IV administration of each of 4 boluses of angiotensin I (20, 100, 500, and 1,000 ng/kg). This protocol was repeated 24 hours after benazepril treatment and telmisartan (3 mg/kg) treatment. Differences in the angiotensin I–induced change in systolic arterial blood pressure (ΔSBP) among treatments were determined. RESULTS At 90 minutes after capsule administration, only losartan did not significantly reduce ΔSBP in response to the 3 higher angiotensin doses, compared with placebo. Among drug treatments, telmisartan (3 mg/kg dosage) attenuated ΔSBP to a significantly greater degree than benazepril and all other treatments. At 24 hours, telmisartan was more effective than benazepril (mean ± SEM ΔSBP, 15.7 ± 1.9 mm Hg vs 55.9 ± 12.42 mm Hg, respectively). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that telmisartan administration may have advantages over benazepril administration for cats with renal or cardiovascular disease.

OBJECTIVE To establish the minimum alveolar concentration (MAC) of desflurane and evaluate the effects of 2 opioids on MAC in sheep. ANIMALS 8 adult nulliparous mixed-breed sheep. PROCEDURES A randomized crossover design was used. Each sheep was evaluated individually on 2 occasions (to allow assessment of the effects of each of 2 opioids), separated by a minimum of 10 days. On each occasion, sheep were anesthetized with desflurane in 100% oxygen, MAC of desflurane was determined, oxymorphone (0.05 mg/kg) or hydromorphone (0.10 mg/kg) was administered IV, and MAC was redetermined. Physiologic variables and arterial blood gas and electrolyte concentrations were measured at baseline (before MAC determination, with end-tidal desflurane concentration maintained at 10%) and each time MAC was determined. Timing of various stages of anesthesia was recorded for both occasions. RESULTS Mean ± SEM MAC of desflurane was 8.6 ± 0.2%. Oxymorphone or hydromorphone administration resulted in significantly lower MAC (7.6 ± 0.4% and 7.9 ± 0.2%, respectively). Cardiac output at MAC determination for desflurane alone and for desflurane with opioid administration was higher than that at baseline. No difference was identified among hematologic values at any point. Effects of oxymorphone and hydromorphone on durations of various stages of anesthesia did not differ significantly. CONCLUSIONS AND CLINICAL RELEVANCE MAC of desflurane in nulliparous adult sheep was established. Intravenous administration of oxymorphone or hydromorphone led to a decrease in MAC; however, the clinical importance of that decrease was minor relative to the effect in other species.

OBJECTIVE To determine effects of IV transfusion with fresh (3-day-old) or stored (35-day-old) autologous erythrocyte concentrate on serum labile iron concentration, iron-binding capacity, and protein interaction with iron in dogs. ANIMALS 10 random-source healthy dogs. PROCEDURES Dogs were randomly assigned to receive autologous erythrocyte concentrate stored for 3 days (n = 5) or 35 days (5). One unit of whole blood was collected from each dog, and erythrocyte concentrates were prepared and stored as assigned. After erythrocyte storage, IV transfusion was performed, with dogs receiving their own erythrocyte concentrate. Blood samples were collected from each dog before and 5, 9, 24, 48, and 72 hours after transfusion. Serum was harvested for measurement of total iron, labile iron, transferrin, ferritin, hemoglobin, and haptoglobin concentrations. RESULTS For dogs that received fresh erythrocytes, serum concentrations of the various analytes largely remained unchanged after transfusion. For dogs that received stored erythrocytes, serum concentrations of total iron, labile iron, hemoglobin, and ferritin increased markedly and serum concentrations of transferrin and haptoglobin decreased after transfusion. CONCLUSIONS AND CLINICAL RELEVANCE Transfusion with autologous erythrocyte concentrate stored for 35 days resulted in evidence of intravascular hemolysis in healthy dogs. The associated marked increases in circulating concentrations of free iron and hemoglobin have the potential to adversely affect transfusion recipients.

OBJECTIVE To evaluate pharmacokinetics of ammonium tetrathiomolybdate (TTM) after IV and oral administration to dogs and effects of TTM administration on trace mineral concentrations. ANIMALS 8 adult Beagles and Beagle crossbreds (4 sexually intact males and 4 sexually intact females). PROCEDURES Dogs received TTM (1 mg/kg) IV and orally in a randomized crossover study. Serum molybdenum and copper concentrations were measured via inductively coupled plasma mass spectrometry in samples obtained 0 to 72 hours after administration. Pharmacokinetics was determined via noncompartmental analysis. RESULTS For IV administration, mean ± SD terminal elimination rate constant, maximum concentration, area under the curve, and half-life were 0.03 ± 0.01 hours−1, 4.9 ± 0.6 μg/mL, 30.7 ± 5.4 μg/mL•h, and 27.7 ± 6.8 hours, respectively. For oral administration, mean ± SD terminal elimination rate constant, time to maximum concentration, maximum concentration, area under the curve, and half-life were 0.03 ± 0.01 hours−1, 3.0 ± 3.5 hours, 0.2 ± 0.4 μg/mL, 6.5 ± 8.0 μg/mL•h, and 26.8 ± 8.0 hours, respectively. Oral bioavailability was 21 ± 22%. Serum copper concentrations increased significantly after IV and oral administration. Emesis occurred after IV (2 dogs) and oral administration (3 dogs). CONCLUSIONS AND CLINICAL RELEVANCE Pharmacokinetics for TTM after a single IV and oral administration was determined for clinically normal dogs. Absorption of TTM after oral administration was variable. Increased serum copper concentrations suggested that TTM mobilized tissue copper. Further studies will be needed to evaluate the potential therapeutic use of TTM in copper-associated chronic hepatitis of dogs.

OBJECTIVE To monitor concentrations of sulfadimidine in the paranasal sinus mucosa (PSM) of unsedated horses following IV administration of trimethoprim-sulfadimidine via in vivo microdialysis. ANIMALS 10 healthy adult horses. PROCEDURES Concentric microdialysis probes were implanted into the subepithelial layers of the frontal sinus mucosa of standing sedated horses. Four hours after implantation, trimethoprim-sulfadimidine (30 mg/kg) was administered IV every 24 hours for 2 days; dialysate and plasma samples were collected at intervals during that 48-hour period and analyzed for concentrations of sulfadimidine. The dialysate concentration and relative loss of sulfadimidine from the perfusate were used to calculate the PSM concentration. RESULTS Microdialysis probe implantation and subsequent in vivo microdialysis were successfully performed for all 10 horses. Following the first and second administration of trimethoprim-sulfadimidine, mean ± SD peak concentrations of sulfadimidine were 55.3 ± 10.3 μg/mL and 51.5 ± 8.7 μg/mL, respectively, in plasma and 9.6 ± 4.5 μg/mL and 7.0 ± 3.3 μg/mL, respectively, in the PSM. Peak sulfadimidine concentrations in the PSM were detected at 5.9 ± 2.7 hours and 5.4 ± 2.3 hours following the first and second drug administrations, respectively. For 12 hours, mean PSM sulfadimidine concentration remained greater than the minimum inhibitory concentration indicative of sulfonamide susceptibility of equine bacterial isolates (4.75 μg/mL). CONCLUSIONS AND CLINICAL RELEVANCE In vivo microdialysis for continuous monitoring of PSM sulfadimidine concentrations in unsedated horses was feasible. Intravenous administration of trimethoprim (5 mg/kg) and sulfadimidine (25 mg/kg) proved likely to be efficient for treating sinusitis caused by highly susceptible pathogens, providing that the dosing interval is 12 hours.