The pharmacokinetics of single-dose oral atorvastatin and its metabolites support therapeutic use in cockatiels (Nymphicus hollandicus).

OBJECTIVE: To evaluate the plasma concentrations and determine the pharmacokinetic parameters of atorvastatin and its primary active metabolites (para- and orthohydroxyatorvastatin) after administration of a single oral dose in cockatiels (Nymphicus hollandicus). ANIMALS: 14 adult cockatiels (7 male, 7 female) around 2 years of age. METHODS: A compounded oral suspension of atorvastatin 10 mg/mL made with an oral suspending agent and an oral sweetener was administered via oral gavage at 20 mg/kg to each bird. Blood samples were collected at 7 different time points from 0.5 to 24 hours postadministration in a balanced incomplete block design with 3 blood samples per bird and 6 replicates per time point. Plasma concentrations of atorvastatin, parahydroxyatorvastatin, and orthohydroxyatorvastatin were determined by liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was performed using noncompartmental analysis. RESULTS: The estimated time to maximum concentration (tmax) for atorvastatin, parahydroxyatorvastatin, and orthohydroxyatorvastatin was 3 hours for each. The estimated maximum plasma concentration (Cmax) for atorvastatin, parahydroxyatorvastatin, and orthohydroxyatorvastatin was 152.6, 172.4, and 68.8 ng/mL, respectively. The terminal half-lives were 4, 6.8, and 4.6 hours, respectively. CLINICAL RELEVANCE: These results support the therapeutic use of atorvastatin at the dose evaluated in this species based on human pharmacokinetic data. A starting dose of 20 mg/kg PO every 12 to 24 hours could be used to treat lipid disorders in cockatiels pending more data on multidose use and hypolipidemic efficacy.

Hepatic lipid accumulation is associated with multiple metabolic pathway alterations but not dyslipidemia and insulin resistance in central bearded dragons (Pogona vitticeps).

OBJECTIVE: To investigate associations between hepatic fat accumulation, fibrosis, and plasma values of primary metabolites, biochemical measurands, insulin, and lipoproteins in bearded dragons. ANIMALS: 48 adult central bearded dragons (Pogona vitticeps). METHODS: Dragons were sedated with alfaxalone, and a blood sample was collected. Plasma was submitted for untargeted primary metabolomics using gas chromatography time-of-flight mass spectrometry, a biochemistry panel, and a lipoprotein panel determined by PAGE. Hepatic lipid content was quantified by liver attenuation measurements from CT images and digital image analysis of standardized histologic sections of the liver. Fibrosis was quantified by digital image analysis on Masson's trichrome-stained histologic sections. Severity was determined from pathologic review of liver sections according to a standardized grading system. Statistical associations were investigated using serial linear models adjusted for false discovery rate and multivariate statistics. RESULTS: Both hepatic fat and fibrosis had a significant effect on CT liver attenuation values. Several oligosaccharides (maltotriose, maltose, ribose, trehalose) and alkaline phosphatase were significantly and linearly increased with hepatic lipid content (all q < .05). On partial least square-discriminant analysis, ß-hydroxybutyric acid was the most important discriminatory variable between fatty liver severity grades on histology. No significant associations were found with insulin, lipoproteins, and succinic acid. CLINICAL RELEVANCE: Bearded dragons with hepatic lipid accumulation experienced multiple metabolic pathway disruptions, some being compatible with mitochondrial dysfunction. No evidence of insulin resistance or dyslipidemia was found. Hepatic biopsy and histopathology remain recommended for reliably diagnosing and staging fatty liver disease in bearded dragons.

Pharmacokinetics of single-dose oral atorvastatin and its metabolites support therapeutic use in orange-winged Amazon parrots (Amazona amazonica).

OBJECTIVE: To evaluate the plasma concentrations and determine pharmacokinetic parameters of atorvastatin and its primary active metabolites (para- and ortho-hydroxyatorvastatin) after administration of a single oral dose in orange-winged Amazon parrots (Amazona amazonica). ANIMALS: 8 adult orange-winged Amazon parrots (4 male, 4 female) of varying ages. METHODS: A compounded oral suspension of atorvastatin 10 mg/mL was administered via oral gavage at 20 mg/kg to each bird. Blood samples were collected at 10 different time points from 0 to 30 hours postadministration to evaluate plasma levels of atorvastatin, para-hydroxyatorvastatin, and ortho-hydroxyatorvastatin. Pharmacokinetic analysis was performed using noncompartmental analysis and commercially available software. RESULTS: Mean ± SD atorvastatin half-life, tmax, and Cmax were 5.96 ± 11.50 hours, 1.60 ± 0.80 hours, and 82.60 ± 58.30 ng/mL, respectively. For para-hydroxyatorvastatin, the half-life, tmax, and Cmax were 6.46 ± 54.20 hours, 5.00 ± 2.51 hours, and 34.10 ± 16.00 ng/mL, respectively, and 5.58 ± 9.92 hours, 3.38 ± 2.10 hours, and 7.35 ± 3.96 ng/mL for ortho-hydroxyatorvastatin. CLINICAL RELEVANCE: The plasma concentrations and pharmacokinetic profile shown support the therapeutic use of atorvastatin at the dose evaluated in this species based on human pharmacokinetic data. While 20 mg/kg PO q24 hours could be used as a starting dosage until further studies evaluating multiple dose administration and efficacy in this species become available, the high interindividual variability results warrant monitoring of the treatment response to make dosing adjustments if needed.

Effects of Atorvastatin and Rosuvastatin on Blood Lipids in Quaker Parrots (Myiopsitta monachus).

Statin drugs are the most effective class of hypolipidemic and antiatherosclerotic drugs, with atorvastatin and rosuvastatin being the most effective. While the use of statins would be a tremendous asset in the treatment of dyslipidemia and lipid-accumulation disorders in birds, there are only limited data available regarding their use and effectiveness in psittacine species. Two consecutive randomized crossover trials on Quaker parrots (Myiopsitta monachus) were performed to study the effect of atorvastatin and rosuvastatin. Ten birds were used in an initial balanced crossover experiment with 5 oral treatments (control; atorvastatin 10 mg/kg q12h and q24h; rosuvastatin 10 mg/kg q12h and q24h) for 2 weeks each. Plasma lipidomics and lipoprotein profiling were performed after each treatment. Twelve birds were used in a second experiment consisting of 2 parallel crossover studies, each with 6 birds either fed their regular diet or a 0.3% cholesterol diet. In the 2 parallel crossover studies, the treatment group was administered atorvastatin 20 mg/kg orally q12h and the control group a placebo suspension orally q12h. Plasma lipidomics, lipoprotein profiles, and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity were subsequently measured. Results were analyzed with serial linear mixed models and trends were assessed graphically. No statistically significant effect of any statin treatment was detected on plasma lipids, lipoproteins, creatinine kinase, or HMG-CoA reductase activity. In the first trial, all the rosuvastatin treatments led to some nonsignificant decreases in several triacylglycerol species, while in the second trial this was only observed in the birds on atorvastatin 20 mg/kg q12h being fed their regular diet. Quaker parrots may require much higher doses of statin drugs to show significant and clinically useful lipid-lowering effects.

Evaluation of Thermal Antinociceptive Effects of Intramuscular Hydromorphone Hydrochloride in Great Horned Owls (Bubo virginianus).

Across the Americas, great horned owls (Bubo virginianus) are often presented to veterinarians for conditions requiring pain management. Although recent studies have evaluated opioid drugs in raptor species, information in Strigiformes is lacking. The objective of this study was to evaluate the analgesic effect and duration of action of hydromorphone hydrochloride, a full µ-opioid receptor agonist, in great horned owls. In a randomized, blinded, balanced crossover study, 6 adult birds (5 females and 1 male) received hydromorphone (0.3 and 0.6 mg/kg) or saline (0.9% NaCl) solution (0.03 mL/kg; control) in the left pectoral muscle, with a 7-day washout interval between treatments. Each bird was assigned an agitation-sedation score, and the thermal foot withdrawal threshold (TFWT) was measured at predetermined times before (t = 0 hours) and after treatment administration (t = 0.5, 1.5, 3, and 6 hours). Measurements of the TFWT were obtained with a test box equipped with a thermal perch, which delivered a gradually increasing temperature 40-62°C (104-143.6°F) to the right plantar surface of the owl's foot. Compared with controls, hydromorphone at 0.3 mg/kg dose resulted in significantly higher mean TFWT at 0.5 hours (P < 0.001), 1.5 hours (P = 0.003), and 3 hours (P = 0.005), whereas the 0.6 mg/kg dose resulted in significantly higher mean TFWT from 0.5 hours (P = 0.035) to 1.5 hours (P = 0.001). Both hydromorphone doses were associated with a significant change in the agitation-sedation score (P = 0.001), consistent with mild to moderate sedation. Two owls were observed tremoring after administration of the 0.6 mg/kg dose, which was not noted after the 0.5-hour timepoint; no other adverse effects were identified. This study offers scientific evidence to support the use of a µ-opioid agonist in great horned owls for pain management. Pharmacokinetics and other pharmacodynamic studies of other pain models evaluating hydromorphone and other opioid drugs in this species are still needed.

Carrageenan-induced inflammation elicits behavioral changes in cockatiels (Nymphicus hollandicus) for potential pain scale development.

OBJECTIVE: To evaluate behaviors associated with inflammatory pain induced by carrageenan injection in the cockatiel and determine interobserver agreement. ANIMALS: 16 adult cockatiels. METHODS: Cockatiels were randomly assigned as either treatment (carrageenan injection) or control (sham injection) group. The treatment group received a subcutaneous injection of 0.05 mL of a 1% lambda carrageenan solution into the left footpad. Following treatment or control procedures, all cockatiels were video recorded individually for 9.5 hours. Ten minutes of video at each of 11 time points postinjection and/or handling were evaluated by 3 different observers. Twenty-five behaviors within 6 categories (resting, locomotion, maintenance, intake, interaction with environment, and limb and body posture) were assessed, in addition to crest position and mentation. Differences in individual behaviors tallies were assessed using serial Wilcoxon sum rank tests. Interobserver agreement was assessed using an intraclass correlation coefficient for a 2-way design for consistency among multiple observers. RESULTS: Treatment cockatiels exhibited significantly increased focal preening (q = .023) and increased burst preening (q = .036), while control cockatiels spent significantly more time in an upright stance (q = .036). Although the remainder of behaviors observed were not statistically significant between groups, additional variables of interest seen more frequently in treatment cockatiels included non-weight-bearing stance, holding of the body low, and being nonvigilant. The level of agreement between observers was variable based on the specific behaviors; nevertheless, the dynamic behaviors were substantial to strong. CLINICAL RELEVANCE: Carrageenan-induced inflammation-associated behaviors may be valuable in developing a pain scale and evaluating mild inflammatory pain in small psittacine species.

COMPARISON OF KETAMINE-MIDAZOLAM AND KETAMINE-MIDAZOLAM-BUTORPHANOL PREMEDICATION PRIOR TO SEVOFLURANE ANESTHESIA IN WOODCHUCKS (MARMOTA MONAX).

Cardiovascular disease is a frequent cause of death in the critically endangered Vancouver Island marmots (Marmota vancouverensis). This warrants the use of anesthetic protocols with minimal cardiovascular adverse effects. In this study, 12 adult male woodchucks (Marmota monax) were used as models for Vancouver Island marmots. The objective was to compare the physiological effects of two premedication protocols during induction and maintenance of anesthesia with sevoflurane. The two premedications were ketamine 10 mg/kg and midazolam 0.5 mg/kg (KM) or ketamine 10 mg/kg, midazolam 0.5 mg/kg, and butorphanol 1.0 mg/kg (KMB), administered intramuscularly prior to mask induction. Each marmot underwent three anesthetic events and protocols were assigned using a blinded randomized crossover design. Heart rate, respiratory rate, oxygen saturation, and body temperature were recorded throughout, and blood gases were assessed following induction. Resistance to induction was scored and time to induction was recorded. Although mask induction with sevoflurane was successful in all events (mean induction time of 2.1 min), KMB premedication resulted in a faster induction (mean induction time reduced by 1.2 ± 0.3 min) and lower resistance scores. Both protocols resulted in significant cardiovascular and respiratory depression; however, animals that received KMB were more hypercapnic than KM by 8.8 ± 2.8 mm Hg (P = 0.03) (mean venous partial pressure of carbon dioxide [PvCO2] for all: 79.9 mm Hg). In conclusion, if shorter induction times are desired, KMB premedication is preferred. However, cardiorespiratory variables including blood pressure should be monitored, and endotracheal intubation is recommended to allow for ETCO2 monitoring and provision of intermittent positive pressure ventilation.

Biomechanics of landing in injured and uninjured chickens and the role of meloxicam.

Birds use their legs and wings when transitioning from aerial to ground locomotion during landing. To improve our understanding of the effects of footpad dermatitis (FPD) and keel bone fracture (KBF) upon landing biomechanics in laying hens, we measured ground-reaction forces generated by hens (n = 37) as they landed on force plates (Bertec Corporation, Columbus, OH) from a 30 cm drop or 170 cm jump in a single-blinded placebo-controlled trial using a cross-over design where birds received an anti-inflammatory (meloxicam, 5 mg/kg body mass) or placebo treatment beforehand. We used generalized linear mixed models to test for effects of health status, treatment and their interaction on landing velocity (m/s), maximum resultant force (N), and impulse (force integrated with respect to time [N s]). Birds with FPD and KBF tended to show divergent alterations to their landing biomechanics when landing from a 30 cm drop, with a higher landing velocity and maximum force in KBF compared to FPD birds, potentially indicative of efforts to either reduce the use of their wings or impacts on inflamed footpads. In contrast, at 170 cm jumps fewer differences between birds of different health statuses were observed likely due to laying hens being poor flyers already at their maximum power output. Our results indicate that orthopedic injuries, apart from being welfare issues on their own, may have subtle influences on bird mobility through altered landing biomechanics that should be considered.

Comparison of Lipoprotein Analysis Using Gel-Permeation High-Performance Liquid Chromatography and a Biochemistry Analyzer in Normolipidemic and Dyslipidemic Quaker Parrots (Myiopsitta monachus).

Lipid accumulation disorders are common in psittacine birds and can be associated with changes in plasma lipoproteins, most notably low-density lipoprotein (LDL) and high-density lipoprotein (HDL). However, lipoprotein analysis by standard laboratory analyzers or an indirect method, such as the Friedewald formula, has not been validated in parrots. A research colony of 12 Quaker parrots (Myiopsitta monachus) were used to compare plasma values from the Roche Cobas c501 biochemistry analyzer for total cholesterol, total triglycerides, LDL, and HDL to gel-permeation high-performance liquid chromatography (GP-HPLC). To increase sample size and broaden the analytical range to include dyslipidemic samples, 2 cross-over studies were performed on a 0.3% cholesterol diet and a 20% fat diet. Agreement between methods was assessed by linear mixed models and Bland and Altman plots. The LDL concentrations calculated by the Friedewald formula and alternative formulas, and the effects of triglycerides on the biases, were also evaluated. Forty-five plasma samples were used. The cholesterol diet induced a marked increase in cholesterol and all lipoproteins, whereas the fat diet did not lead to dyslipidemia. Direct and indirect LDL measurements obtained with the clinical analyzer were not in clinical agreement with GP-HPLC, whereas HDL had acceptable agreement for normotriglyceridemic samples. Hypertriglyceridemic plasma samples were found to interfere with lipoprotein measurements. This study found LDL measured by the Roche Cobas c501 biochemistry analyzer and indirect estimations cannot be recommended in the Quaker parrot, and non-HDL cholesterol should be used instead. Lipoprotein panels obtained from hypertriglyceridemic samples should be interpreted with care.

Twice-daily oral administration of a cannabidiol and cannabidiolic acid-rich hemp extract was well tolerated in orange-winged Amazon parrots (Amazona amazonica) and has a favorable pharmacokinetic profile.

OBJECTIVE: To determine the pharmacokinetics of 8 cannabinoids and 5 metabolites after oral administration of single and multiple doses of a cannabidiol (CBD)-cannabidiolic acid (CBDA)-rich hemp extract to orange-winged Amazon parrots (Amazona amazonica) as well as to evaluate the extract's adverse effects. ANIMALS: 12 birds. PROCEDURES: Based on pilot studies, a single-dose study based on 30/32.5 mg/kg of cannabidiol/cannabidiolic acid of a hemp extract was administered orally to 8 fasted parrots, and 10 blood samples were collected over 24 hours after administration. After a 4-week washout period, the hemp extract was administered orally to 7 birds at the previous dose every 12 hours for 7 days, and blood samples were collected at the previous time points. Cannabidiol, Δ9-tetrahydrocannabinol, cannabinol, cannabichromene, cannabigerol, cannabidiolic acid, cannabigerolic acid, Δ9-tetrahydrocannabinolic acid, and 5 specific metabolites were measured by liquid chromatography-tandem/mass-spectrometry, and pharmacokinetic parameters were calculated. Adverse effects and changes in the plasma biochemistry and lipid panels were evaluated. RESULTS: Pharmacokinetic parameters for cannabidiol, cannabidiolic acid, Δ9-tetrahydrocannabinol, Δ9-tetrahydrocannabinolic acid, and the metabolite 11-hydroxy-9-tetrahydrocannabinol were established. For the multiple-dose study, cannabidiol/cannabidiolic acid mean Cmax was 337.4/602.1 ng/mL with a tmax of 30 minutes and a terminal half-life of 8.6/6.29 hours, respectively. No adverse effects were detected during the multidose study. The predominant metabolite was 11-hydroxy-9-tetrahydrocannabinol. CLINICAL RELEVANCE: Twice daily oral administration of the hemp extract based on 30 mg/kg/32.5 mg/kg of cannabidiol/cannabidiolic acid was well tolerated and maintained plasma concentrations considered to be therapeutic in dogs with osteoarthritis. Findings suggest different cannabinoid metabolism from mammals.

Association of plasma metabolites and diagnostic imaging findings with hepatic lipidosis in bearded dragons (Pogona vitticeps) and effects of gemfibrozil therapy.

OBJECTIVES: To evaluate the association between plasma metabolites, biochemical analytes, diagnostic imaging findings, and the histologic diagnosis of hepatic lipidosis in bearded dragons. To assess the effects of gemfibrozil therapy on hepatic lipid accumulation and associated diagnostic tests. ANIMALS: Fourteen bearded dragons (Pogona vitticeps) with varying severity of hepatic lipid accumulation (with and without hepatic lipidosis) were included. PROCEDURES: Animals underwent coelomic ultrasound, computed tomography (CT) scans, and coelioscopic hepatic biopsies. Clinical pathology tests included lipidologic tests, hepatic biomarkers, and mass spectrometry-based metabolomics. Animals were medicated with gemfibrozil 6mg/kg orally once a day for 2 months in a randomized blinded clinical trial prior to repeating previous diagnostic testing. RESULTS: Hounsfield units on CT were negatively associated with increased hepatic vacuolation, while ultrasound and gross evaluation of the liver were not reliable. Beta-hydroxybutyric-acid (BHBA) concentrations were significantly associated with hepatic lipidosis. Metabolomics and lipidomics data found BHBA and succinic acid to be potential biomarkers for diagnosing hepatic lipidosis in bearded dragons. Succinic acid concentrations were significantly lower in the gemfibrozil treatment group. There was a tendency for improvement in the biomarkers and reduced hepatic fat in bearded dragons with hepatic lipidosis when treated with gemfibrozil, though the improvement was not statistically significant. CONCLUSIONS: These findings provide information on the antemortem assessment of hepatic lipidosis in bearded dragons and paves the way for further research in diagnosis and treatment of this disease.

Comparison between mainstream (Capnostat 5) and a low-flow sidestream capnometer (Capnostream) in mechanically ventilated, sevoflurane-anesthetized rabbits using a Bain coaxial delivery system.

OBJECTIVE: To evaluate agreement between end-tidal carbon dioxide (Pe'CO2) and PaCO2 with sidestream and mainstream capnometers in mechanically ventilated anesthetized rabbits, with two ventilatory strategies. STUDY DESIGN: Prospective experimental study. ANIMALS: A total of 10 New Zealand White rabbits weighing 3.6 ± 0.3 kg (mean ± standard deviation). METHODS: Rabbits anesthetized with sevoflurane were intubated with an uncuffed endotracheal tube (3.0 mm internal diameter) and adequate seal. For Pe'CO2, the sidestream capnometer sampling adapter or the mainstream capnometer was placed between the endotracheal tube and Bain breathing system (1.5 L minute-1 oxygen). PaCO2 was obtained from arterial blood collected every 5 minutes. A time-cycled ventilator delivered an inspiratory time of 1 second and 12 or 20 breaths minute-1. Peak inspiratory pressure was initially set to achieve Pe'CO2 normocapnia of 35-45 mmHg (4.6-6.0 kPa). A total of five paired Pe'CO2 and PaCO2 measurements were obtained with each ventilation mode for each capnometer. Anesthetic episodes were separated by 7 days. Agreement was assessed using Bland-Altman analysis and linear mixed models; p < 0.05. RESULTS: There were 90 and 83 pairs for the mainstream and sidestream capnometers, respectively. The mainstream capnometer underestimated PaCO2 by 12.6 ± 2.9 mmHg (proportional bias 0.44 ± 0.06 mmHg per 1 mmHg PaCO2 increase). With the sidestream capnometer, ventilation mode had a significant effect on Pe'CO2. At 12 breaths minute-1, Pe'CO2 underestimated PaCO2 by 23.9 ± 8.2 mmHg (proportional bias: 0.81 ± 0.18 mmHg per 1 mmHg PaCO2 increase). At 20 breaths minute-1, Pe'CO2 underestimated PaCO2 by 38.8 ± 5.0 mmHg (proportional bias 1.13 ± 0.10 mmHg per 1 mmHg PaCO2 increase). CONCLUSIONS AND CLINICAL RELEVANCE: Both capnometers underestimated PaCO2. The sidestream capnometer underestimated PaCO2 more than the mainstream capnometer, and was affected by ventilation mode.

Some cardiopulmonary effects of capnoperitoneum in anesthetized guinea pigs (Cavia porcellus): spontaneous ventilation versus intubation and mechanical ventilation.

OBJECTIVE: To compare cardiopulmonary variables and blood gas analytes in guinea pigs (Cavia porcellus) during anesthesia with and without abdominal carbon dioxide (CO2) insufflation at intra-abdominal pressures (IAPs) 4 and 6 mmHg, with and without endotracheal intubation. STUDY DESIGN: Prospective experimental trial. ANIMALS: A total of six intact female Hartley guinea pigs. METHODS: A crossover study with sequence randomization for IAP and intubation status was used. The animals were sedated with intramuscular midazolam (1.5 mg kg-1) and buprenorphine (0.2 mg kg-1) and anesthetized with isoflurane, and an abdominal catheter was inserted for CO2 insufflation. Animals with endotracheal intubation were mechanically ventilated and animals maintained using a facemask breathed spontaneously. After 15 minutes of insufflation, the following variables were obtained at each IAP: pulse rate, respiratory rate, rectal temperature, oxygen saturation, end-tidal CO2 (intubated only), peak inspiratory pressure (intubated only), noninvasive blood pressure and blood gas and electrolyte values, with a rest period of 5 minutes between consecutive IAPs. After 4 weeks, the procedure was repeated with the guinea pigs assigned the opposite intubation status. RESULTS: Intubated guinea pigs had significantly higher pH and lower partial pressure of CO2 in cranial vena cava blood (PvCO2) than nonintubated guinea pigs. An IAP of 6 mmHg resulted in a significantly higher PvCO2 (65.9 ± 19.0 mmHg; 8.8 ± 2.5 kPa) than at 0 (53.2 ± 17.2 mmHg; 7.1 ± 2.3 kPa) and 4 mmHg (52.6 ± 10.8 mmHg; 7.01 ± 1.4 kPa), mean ± standard deviation, with intubated and nonintubated animals combined. CONCLUSIONS AND CLINICAL RELEVANCE: Although the oral anatomy of guinea pigs makes endotracheal intubation difficult, capnoperitoneum during anesthesia induces marked hypercapnia in the absence of mechanical ventilation. An IAP of 4 mmHg should be further evaluated for laparoscopic procedures in guinea pigs because hypercapnia may be less severe than with 6 mmHg.

Morphological features of hepatic lipid changes in bearded dragons (Pogona vitticeps), and a proposed grading system.

Hepatic lipidosis is commonly diagnosed in pet bearded dragons (Pogona vitticeps). However, there are no studies detailing the histological features of hepatic lipid changes in this species. This study describes the microscopic features of lipid change and details an associated scoring system. Histologic hepatic sections were retrospectively evaluated from 252 bearded dragons submitted for necropsy. Pathologic assessment was used to develop a grading scheme with 2 qualitative, 1 quantitative, and 6 semi-quantitative microscopic parameters, which were refined based on variability. The final grading system developed for diffuse and panlobular lipid accumulation included 2 semi-quantitative and 1 quantitative categories: percentage of hepatocellular vacuolation, fibrosis, and hepatocellular swelling, respectively. Hepatocellular swelling was indirectly quantified by counting the number of nuclei per unit area. There was a strong positive correlation (P < .001) between the percentage of hepatocellular vacuolation and lipid content, a strong negative correlation (P < .001) between nuclear count and lipid content, and a moderate correlation (P < .001) between fibrosis and lipid content. Each category was given a numerical value ranging from 0 to 4, with the sum of each representing the final grade. Cutoff values stratified microscopic changes into mild (final grade 1-4), moderate (5-7), and severe (≥8). There was strong interrater agreement for assessment of vacuolization, fibrosis, and severity classification and moderate for hepatocellular swelling. This study documents the features of hepatic lipid changes in bearded dragons. Although a cutoff to differentiate pathologic from nonpathologic lipid accumulation could not be estimated, the proposed grading scheme can be used to inform future studies.

Prevalence and risk factors of hepatic lipid changes in bearded dragons (Pogona vitticeps).

Hepatic lipidosis is a common disease of captive bearded dragons (Pogona vitticeps). Diagnosis, prevention, and treatment of this condition are challenging, as there is minimal information in the literature. Our study determined the prevalence and epidemiological risk factors associated with the grade and severity of hepatic lipid changes in bearded dragons submitted for necropsy in 2 North American institutions. A total of 571 postmortem cases were retrieved, and from each pathology report the demographic data (age, sex) and the list of final diagnoses were extracted. For each case diagnosed with hepatic lipidosis, the archived sections of liver were reviewed and the severity of lipid change was stratified using a standardized histologic grading system. Descriptive statistics were used to estimate the prevalence of each grade and severity class. Associations between grade and severity, as well as demographic data and concurrent diseases, were explored using ordinal logistic regression analysis. On multiple logistic models, the occurrence of infectious disease and neoplasia was associated with decreased grade and severity of hepatic lipid changes, while the female sex and adult age were associated with an increased grade and severity. None of the other variables were significantly associated with hepatic lipid changes. These results suggest that reproductively active females and adult bearded dragons are predisposed to increasing hepatic lipid changes, while those with an underlying disease process have reduced hepatic lipid accumulation and changes, possibly due to increased fat catabolism. Data in this study can serve to benchmark the prevalence of hepatic lipidosis in bearded dragons and allow further investigations.

Evaluation of Oral Transmucosal Administration of Pentobarbital for Euthanasia of Conscious Wild Birds.

This prospective study evaluated oral transmucosal pentobarbital sodium at three doses in 110 wild-caught wild birds requiring euthanasia. Birds received transmucosal pentobarbital at five (430 mg/kg), six (516 mg/kg), and seven times (602 mg/kg) the intravenous dose for mammals. Time to first effects and loss of consciousness, presence of pupillary light and corneal reflexes, apnea, and asystole were recorded each minute. When asystole was not achieved at 5 minutes, IV pentobarbital was administered. Combining data for all doses, loss of consciousness occurred at a median (range) of 2 minutes (0-4.75 min), apnea at 3 minutes (0-6 min), and asystole at 4 minutes (0.5-5 min). Loss of consciousness and apnea occurred significantly faster in the 602 mg/kg dose group than in the 430 mg/kg group (p = 0.009, difference of 0.6 ± 0.2 min; p = 0.024, difference of 0.7 ± 0.3 min), respectively. Apnea and asystole were achieved in 80/110 birds within 5 minutes. Oral transmucosal pentobarbital results in rapid loss of consciousness and respiratory arrest and provides a reliable alternative euthanasia method compared to intravenous administration.

Comparison of blood leptin and vitamin E and blood and adipose fatty acid compositions in wild and captive populations of critically endangered Vancouver Island marmots (Marmota vancouverensis).

Vancouver Island marmots (Marmota vancouverensis) (VIMs) are a critically endangered species of fat-storing hibernators, endemic to Vancouver Island, British Columbia, Canada. In addition to in-situ conservation efforts, a captive breeding program has been ongoing since 1997. The captive diet is mostly pellet-based and rich in n-6 polyunsaturated fatty acids (PUFAs). In captivity, overall length of hibernation is shortened, and marmots have higher adipose tissue reserves compared to their wild-born counterparts, which may be a risk factor for cardiovascular disease, the leading cause of mortality in captive marmots. To investigate differences in lipid metabolism between wild and captive populations of VIMs, blood vitamin E, fatty acid (FA) profiles and leptin, and white adipose tissue (WAT) FA profiles were compared during the active season (May to September 2019). Gas chromatography, high-performance liquid chromatography, and multiplex kits were used to obtain FA profiles, α-tocopherol, and leptin values, respectively. In both plasma and WAT, the concentration of the sum of all FA in the total lipids was significantly increased in captive VIMs. The n-6/n-3 ratio, saturated FAs, and n-6 PUFAS were higher in captive marmots, whereas n-3 PUFAs and the HUFA score were higher in wild marmots. Serum concentrations of α-tocopherol were greater by an average of 45% in captive marmots, whereas leptin concentrations did not differ. Results from this study may be applied to improve the diet and implement weight management to possibly enhance the quality of hibernation and decrease the risk of cardiovascular and metabolic diseases of captive VIMs.

Blood Lipid Diagnostics in Psittacine Birds.

Lipids are the main biomolecular constituents of plasma and occupy a central place in the pathophysiology of several common diseases of parrots. Dyslipidemias frequently occur in psittacine birds in relation to a variety of lipid accumulation disorders and female reproductive disorders. The five main lipid classes in the plasma are sterols, fatty acyls, glycerolipids, glycerophospholipids, and sphingolipids. Most lipids are transported in the blood within lipoproteins. Lipidologic diagnostic tests to characterize dyslipidemias and risk factors of lipid disorders include routine biochemical tests such as cholesterol and triglycerides, lipoprotein testing, and newer comprehensive techniques to assess whole lipid pathways using lipidomics.

Assessment of laparoscopic working space in guinea pigs (Cavia porcellus) undergoing carbon dioxide insufflation at different intra-abdominal pressures.

OBJECTIVE: To evaluate pneumoperitoneal volumes (laparoscopic working space) in guinea pigs (Cavia porcellus) undergoing pneumoperitoneum via carbon dioxide insufflation at different intra-abdominal pressures (IAPs) (4, 6, and 8 mm Hg) and recumbencies (dorsal, right lateral, and left lateral). ANIMALS: Six 3- to 4-month-old sexually intact female Hartley guinea pigs. PROCEDURES: Guinea pigs were anesthetized, intubated, and had an abdominal insufflation catheter placed. A baseline abdominal CT scan was performed. Guinea pigs underwent insufflation, with each IAP given in a random order for 10 to 15 minutes with a washout period of 5 minutes between pressures. Abdominal CT scans were acquired at each IAP and at each recumbency. Pneumoperitoneal volumes were calculated using software. RESULTS: Increases in IAP increased working space significantly (P < .001). The 6- and 8-mm Hg pressures increased working space from 4 mm Hg by 7.3% and 19.8%, respectively. Recumbent positioning (P = .60) and body weight (P = .73) did not affect working space. Order of IAP had a significant (P = .006) effect on working space. One of the guinea pigs experienced oxygen desaturation and bradycardia at 6- and 8-mm Hg IAP. CLINICAL RELEVANCE: Although an increased working space occurred at 6 and 8 mm Hg compared to 4 mm Hg, further research is needed concerning the cardiovascular effects of pneumoperitoneum in guinea pigs to determine whether those higher IAPs are safe in this species. An IAP of 6 mm Hg can be considered for laparoscopic cannula placement, followed by a lower IAP for laparoscopic procedures.

Anesthetic effects of alfaxalone-ketamine-midazolam and alfaxalone-ketamine-dexmedetomidine administered intramuscularly in black-tailed prairie dogs (Cynomys ludovicianus).

OBJECTIVE: To evaluate and compare the anesthetic effects of alfaxalone-ketamine-midazolam (AKM) and alfaxalone-ketamine-dexmedetomidine (AKD) in black-tailed prairie dogs (Cynomys ludovicianus). ANIMALS: 9 male black-tailed prairie dogs. PROCEDURES: Prairie dogs were anesthetized with AKM (6 mg/kg alfaxalone, 30 mg/kg ketamine, and 1.5 mg/kg midazolam) and AKD (6 mg/kg alfaxalone, 30 mg/kg ketamine, and 0.15 mg/kg dexmedetomidine) in a prospective, complete cross-over study. Atipamezole (1.5 mg/kg) after AKD or flumazenil (0.1mg/kg) after AKM was administered 45 minutes after induction of anesthesia. Onset of general anesthesia, physiologic parameters, depth of anesthesia, and time to recovery after reversal administration were evaluated for each treatment. RESULTS: Both AKM and AKD produced a deep plane of anesthesia in black-tailed prairie dogs that varied in duration. The median induction times for AKM and AKD were 82 and 60 seconds, respectively. The median recovery times for AKM and AKD were 27 and 21 minutes, respectively. There were no significant differences between protocols for induction (P = .37) and recovery (P = .51) times. All measured reflexes were absent in all animals at 5 minutes postinduction, with hindlimb reflexes returning prior to forelimb reflexes. Heart rate was lower but respiratory rate was higher in the AKD treatment. Body temperature decreased significantly for both protocols (P < .001) and was significantly lower with AKM than AKD (P < .001). CLINICAL RELEVANCE: Both AKM and AKD produced a deep plane of anesthesia in black-tailed prairie dogs. For both protocols, heat support and oxygen support are indicated.