Objective-To determine whether dilution of blood samples from healthy dogs with 2 hydroxyethyl starch (HES) solutions, HES 130/0.4 and HES 200/0.5, would result in platelet dysfunction as measured by closure time (Ct) beyond a dilutional effect. Sample-Citrated blood samples from 10 healthy dogs with a Ct within reference limits (52 to 86 seconds). Procedures-Blood samples were diluted 1:9 and 1:3 with 6% HES 130/0.4 and 10% HES 200/0.5 solutions and saline (0.9% NaCl) solution. Dilutions at 1:9 and 1:3 mimicked 10 mL/kg and 30 mL/kg doses, respectively, ignoring in vivo redistribution. Closure time was measured with a platelet function analyzer and compared among dilutions. Results-A dilutional effect on Ct was evident for the 1:3 dilution, compared with the 1:9 dilution, but only HES 200/0.5 increased the Ct beyond the dilutional effect at the 1:3 dilution, to a median Ct of 125 seconds (interquartile range, 117.5 to 139.5 seconds). No effect of HES or dilution on Ct was identified at the 1:9 dilution. Conclusions and Clinical Relevance-1:3 dilution of blood samples from healthy dogs with HES 200/0.5 but not HES 130/0.4 significantly increased Ct beyond the dilutional effect, suggesting that IV administration of HES 200/0.5 in dogs might cause platelet dysfunction.

Objective: To compare the effects of 2 fractions of inspired oxygen, 50% and > 95%, on ventilation, ventilatory rhythm, and gas exchange in isoflurane-anesthetized horses. Animals: 8 healthy adult horses. Procedures: In a crossover study design, horses were assigned to undergo each of 2 anesthetic sessions in random order, with 1 week separating the sessions. In each session, horses were sedated with xylazine hydrochloride (1.0 mg/kg, IV) and anesthesia was induced via IV administration of diazepam (0.05 mg/kg) and ketamine (2.2 mg/kg) Anesthesia was subsequently maintained with isoflurane in 50% or > 95% oxygen for 90 minutes. Measurements obtained during anesthesia included inspiratory and expiratory peak flow and duration, tidal volume, respiratory frequency, end-tidal CO2 concentration, mixed expired partial pressures of CO2 and O2, Pao2, Paco2, blood pH, arterial O2 saturation, heart rate, and arterial blood pressure. Calculated values included the alveolar partial pressure of oxygen, alveolar-to-arterial oxygen tension gradient (Pao2 − Pco2), rate of change of Pao2 − Pao2, and physiologic dead space ratio. Ventilatory rhythm, based on respiratory rate and duration of apnea, was continuously observed and recorded. Results: Use of the lower inspired oxygen fraction of 50% resulted in a lower arterial oxygen saturation and Pao2 than did use of the higher fraction. No significant difference in Paco2, rate of change of Pao2 − Pao2, ventilatory rhythm, or other measured variables was observed between the 2 sessions. Conclusion and Clinical Relevance: Use of 50% inspired oxygen did not improve the ventilatory rhythm or gas exchange and increased the risk of hypoxemia in spontaneously breathing horses during isoflurane anesthesia. Use of both inspired oxygen fractions requires adequate monitoring and the capacity for mechanical ventilation.

Objective-To characterize and quantitatively assess the typical pulmonary anatomy of healthy adult alpacas with multidetector row CT. Animals-10 clinically normal adult female alpacas. Procedures-CT examination of the thorax was performed before and after IV administration of iodinated contrast medium in sedated alpacas in sternal recumbency. Measurements of the trachea, bronchi and related blood vessels, and selected vertebrae as well as the extent and density of lung parenchyma were performed with a Digital Imaging and Communications in Medicine (DICOM) viewer. Morphometric and quantitative data were summarized. Results-Separation of individual lung lobes could not be identified, except for the accessory lung lobe. In all alpacas, both lungs extended farther caudally at the medial aspect than at the lateral aspect. The right lung extended farther in both cranial and caudal directions than did the left lung. The branching pattern of the bronchial tree varied only slightly among alpacas and consisted of 1 cranial bronchus and 3 caudal bronchi bilaterally, with a right accessory bronchus. Luminal diameters of first-generation bronchi ranged from 3 to 9 mm. Mean +/- SD parenchymal lung density was −869 +/- 40 Hounsfield units (HU) before contrast injection and −825 +/- 51 HU after contrast injection. Mean difference in diameter between bronchi and associated arteries or veins was 0.8 +/- 0.9 mm. Conclusions and Clinical Relevance-Knowledge of the typical anatomy of the lungs and bronchial tree in healthy alpacas as determined via CT will aid veterinarians in clinical assessment and bronchoscopic evaluation of alpacas.

Objective: To compare pharmacokinetics after IV, IM, and oral administration of a single dose of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis). Animals: 11 healthy parrots. Procedures: Cohorts of 8 of the 11 birds comprised 3 experimental groups for a crossover study. Pharmacokinetics were determined from plasma concentrations measured via high-performance liquid chromatography after IV, IM, and oral administration of meloxicam at a dose of 1 mg/kg. Results: Initial mean ± SD plasma concentration of 17.3 ± 9.0 μg/mL was measured 5 minutes after IV administration, whereas peak mean concentration was 9.3 ± 1.8 μg/mL 15 minutes after IM administration. At 12 hours after administration, mean plasma concentrations for IV (3.7 ± 2.5 μg/mL) and IM (3.5 ± 2.2 μg/mL) administration were similar. Peak mean plasma concentration (3.5 ± 1.2 μg/mL) was detected 6 hours after oral administration. Absolute systemic bioavailability of meloxicam after IM administration was 100% but was lower after oral administration (range, 49% to 75%). Elimination half-lives after IV, IM, and oral administration were similar (15.9 ± 4.4 hours, 15.1 ± 7.7 hours, and 15.8 ± 8.6 hours, respectively). Conclusions and Clinical Relevance: Pharmacokinetic data may provide useful information for use of meloxicam in Hispaniolan Amazon parrots. A mean plasma concentration of 3.5 μg/mL would be expected to provide analgesia in Hispaniolan Amazon parrots; however, individual variation may result in some birds having low plasma meloxicam concentrations after IV, IM, or oral administration. After oral administration, meloxicam concentration slowly reached the target plasma concentration, but that concentration was not sustained in most birds.

Objective-To test the hypothesis that inflammatory responses to endotoxemia differ between healthy horses and horses with equine metabolic syndrome (EMS). Animals-6 healthy horses and 6 horses with EMS. Procedures-Each horse randomly received an IV infusion of lipopolysaccharide (20 ng/kg [in 60 mL of sterile saline {0.9% NaCl} solution]) or saline solution, followed by the other treatment after a 7-day washout period. Baseline data were obtained 30 minutes before each infusion. After infusion, a physical examination was performed hourly for 9 hours and at 15 and 21 hours; a whole blood sample was collected at 30, 60, 90, 120, 180, and 240 minutes for assessment of inflammatory cytokine gene expression. Liver biopsy was performed between 240 and 360 minutes after infusion. Results-Following lipopolysaccharide infusion in healthy horses and horses with EMS, mean rectal temperature, heart rate, and respiratory rate increased, compared with baseline findings, as did whole blood gene expression of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-α. The magnitude of blood cytokine responses did not differ between groups, but increased expression of IL-6, IL-8, IL-10, and tumor necrosis factor-α persisted for longer periods in EMS-affected horses. Lipopolysaccharide infusion increased liver tissue gene expressions of IL-6 in healthy horses and IL-8 in both healthy and EMS-affected horses, but these gene expressions did not differ between groups. Conclusions and Clinical Relevance-Results supported the hypothesis that EMS affects horses’ inflammatory responses to endotoxin by prolonging cytokine expression in circulating leukocytes. These findings are relevant to the association between obesity and laminitis in horses with EMS.

Objective: To establish an in vivo method for matrix metalloproteinase (MMP)-2 and MMP-9 induction in horses via IV administration of lipopolysaccharide (LPS) and to evaluate the ability of doxycycline, oxytetracycline, flunixin meglumine, and pentoxifylline to inhibit equine MMP-2 and MMP-9 production. Animals: 29 adult horses of various ages and breeds and either sex. Procedures: In part 1, horses received an IV administration of LPS (n = 5) or saline (0.9% NaCl) solution (5). Venous blood samples were collected before and at specified times for 24 hours after infusion. Plasma was harvested and analyzed for MMP-2 and MMP-9 activities via zymography. In part 2, horses received doxycycline (n = 5), oxytetracycline (5), flunixin meglumine (5), or pentoxifylline (4) before and for up to 12 hours after administration of LPS. Plasma was obtained and analyzed, and results were compared with results from the LPS-infused horses of part 1. Results: Administration of LPS significantly increased MMP-2 and MMP-9 activities in the venous circulation of horses. All MMP inhibitors significantly decreased LPS-induced increases in MMP activities but to differing degrees. Pentoxifylline and oxytetracycline appeared to be the most effective MMP-2 and MMP-9 inhibitors, whereas doxycycline and flunixin meglumine were more effective at inhibiting MMP-2 activity than MMP-9 activity. Conclusions and Clinical Relevance: IV administration of LPS to horses caused increased venous plasma activities of MMP-2 and MMP-9. These MMP activities were reduced by pentoxifylline and oxytetracycline, suggesting that further evaluation of these medications for treatment and prevention of MMP-associated diseases in horses is indicated.

Objective-To compare effects of anesthetic induction with midazolam-propofol or midazolam-etomidate on intraocular pressure (IOP), pupillary diameter (PD), pulse rate, blood pressure, and respiratory rate in clinically normal dogs. Animals-18 dogs. Procedures-Dogs undergoing ophthalmic surgery received midazolam (0.2 mg/kg, IV) and either propofol or etomidate (IV) until intubatable. For all dogs, results of physical examinations, ophthalmic examinations of the nonoperated eye, and preanesthetic blood analyses were normal. Intraocular pressure, PD, blood pressure, pulse rate, and respiratory rate were measured in the nonoperated eye at 5 time points: just prior to the anesthetic induction sequence, after 5 minutes of preanesthetic oxygenation via face mask, after IV administration of midazolam, after IV anesthetic induction, and after endotracheal intubation. Results-PD decreased significantly from baseline by 4.4 +/- 0.4 mm (mean +/- SD) after anesthetic induction and 5.3 +/- 0.4 mm after intubation in the etomidate group and by 1. 2 +/- 0.4 mm after intubation in the propofol group. Intraocular pressure was increased significantly from baseline by 3.2 +/- 1.0 mm Hg after anesthetic induction in the etomidate group and by 4.7 +/- 1.2 mm Hg after anesthetic induction and 4.5 +/- 1. 2 mm Hg after intubation in the propofol group. Pulse rate was significantly lower by 28.6 +/- 12.6 beats/min after anesthetic induction in the etomidate group, compared with the propofol group. Conclusions and Clinical Relevance-At the studied doses, midazolam-etomidate caused clinically important miosis and increased IOP. Midazolam-propofol caused an even greater increase in IOP but had minimal effects on PD.

Objective: To describe the pharmacokinetics of N-acetylcysteine (NAC) in healthy cats after oral and IV administration. Animals: 6 healthy cats. Procedures: In a crossover study, cats received NAC (100 mg/kg) via IV and oral routes of administration; there was a 4-week washout period between treatments. Plasma samples were obtained at 0, 5, 15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 36, and 48 hours after administration, and NAC concentrations were quantified by use of a validated high-performance liquid chromatography–mass spectrometry protocol. Data were analyzed via compartmental and noncompartmental pharmacokinetic analysis. Results: Pharmacokinetics for both routes of administration were best described by a 2-compartment model. Mean ± SD elimination half-life was 0.78 ± 0.16 hours and 1.34 ± 0.24 hours for the IV and oral routes of administration, respectively. Mean bioavailability of NAC after oral administration was 19.3 ± 4.4%. Conclusions and Clinical Relevance: The pharmacokinetics of NAC for this small population of healthy cats differed from values reported for humans. Assuming there would be similar pharmacokinetics in diseased cats, dose extrapolations from human medicine may result in underdosing of NAC in cats with acute disease. Despite the low bioavailability, plasma concentrations of NAC after oral administration at 100 mg/kg may be effective in the treatment of chronic diseases.

Objective: To determine the pharmacokinetics of meloxicam after IV and PO administration to 6 healthy sheep. Animals: 6 healthy adult Dorset cross sheep (5 males and 1 female). Procedures: Meloxicam (0.5 mg/kg, IV, or 1.0 mg/kg, PO) was administered in a randomized crossover design with a 10-day washout period. Blood samples were collected at predetermined times over 96 hours. Serum drug concentrations were determined by high-pressure liquid chromatography with mass spectrometry. Computer software was used to estimate values of pharmacokinetic parameters through noncompartmental methods. Results: Following IV administration (n = 5), the geometric mean (range) elimination half-life was 14.0 hours (10.5 to 17.0 hours), volume of distribution was 0.204 L/kg (0.171 to 0.272 L/kg), and clearance was 0.17 mL/min/kg (0.12 to 0.27 mL/min/kg). Following oral administration (n = 6), maximum serum concentration was 1.72 μg/mL (1.45 to 1.93 μg/mL), time to maximum serum concentration was 19.0 hours (12.0 to 24.0 hours), clearance per bioavailability was 0.22 mL/min/kg (0.16 to 0.30 mL/min/kg), and terminal half-life was 15.4 hours (13.2 to 17.7 hours). Bioavailability of orally administered meloxicam was calculated as 72% (40% to 125%; n = 5). No adverse effects were evident following meloxicam administration via either route. Conclusions and Clinical Relevance: Meloxicam administered PO at 1.0 mg/kg has good bioavailability with slow elimination kinetics in sheep. These data suggested that meloxicam may be clinically useful, provided the safety and analgesic efficacy of meloxicam as well as feed-related influences on its pharmacokinetics are established in ruminants.

Objective: To determine pharmacokinetic and pharmacodynamic properties of midazolam after IV and IM administration in alpacas. Animals: 6 healthy alpacas. Procedures: Midazolam (0.5 mg/kg) was administered IV or IM in a randomized crossover design. Twelve hours prior to administration, catheters were placed in 1 (IM trial) or both (IV trial) jugular veins for drug administration and blood sample collection for determination of serum midazolam concentrations. Blood samples were obtained at intervals up to 24 hours after IM and IV administration. Midazolam concentrations were determined by use of tandem liquid chromatography–mass spectrometry. Results: Maximum concentrations after IV administration (median, 1,394 ng/mL [range, 1,150 to 1,503 ng/mL]) and IM administration (411 ng/mL [217 to 675 ng/mL]) were measured at 3 minutes and at 5 to 30 minutes, respectively. Distribution half-life was 18.7 minutes (13 to 47 minutes) after IV administration and 41 minutes (30 to 80 minutes) after IM administration. Elimination half-life was 98 minutes (67 to 373 minutes) and 234 minutes (103 to 320 minutes) after IV and IM administration, respectively. Total clearance after IV administration was 11.3 mL/min/kg (6.7 to 13.9 mL/min/kg), and steady-state volume of distribution was 525 mL/kg (446 to 798 mL/kg). Bioavailability of midazolam after IM administration was 92%. Peak onset of sedation occurred at 0.4 minutes (IV) and 15 minutes (IM). Sedation was significantly greater after IV administration. Conclusions and Clinical Relevance: Midazolam was well absorbed after IM administration, had a short duration of action, and induced moderate levels of sedation in alpacas.