Objective: To determine repeatability of a wireless, inertial sensor–based lameness evaluation system in horses. Animals: 236 horses. Procedures: Horses were from 2 to 29 years of age and of various breeds and lameness disposition. All horses were instrumented with a wireless, inertial sensor-based motion analysis system on the head (accelerometer), pelvis (midline croup region [accelerometer]), and right forelimb (gyroscope) before evaluation in 2 consecutive trials, approximately 5 minutes apart, as the horse was trotted in a straight line. Signal-processing algorithms generated overall trial asymmetry measures for vertical head and pelvic movement and stride-by-stride differences in head and pelvic maximum and minimum positions between right and left sides of each stride. Repeatability was determined, and trial difference was determined for groups of horses with various numbers of strides for which data were collected per trial. Results: Inertial sensor–based measures of torso movement asymmetry were repeatable. Repeatability for measures of torso asymmetry for determination of hind limb lameness was slightly greater than that for forelimb lameness. Collecting large numbers of strides degraded stride-to-stride repeatability but did not degrade intertrial repeatability. Conclusions and Clinical Relevance: The inertial sensor system used to measure asymmetry of head and pelvic movement as an aid in the detection and evaluation of lameness in horses trotting in a straight line was sufficiently repeatable to investigate for clinical use.

Objective—To identify and characterize cytochrome P450 enzymes (CYPs) responsible for the metabolism of racemic ketamine in 3 mammalian species in vitro by use of chemical inhibitors and antibodies. Sample—Human, canine, and equine liver microsomes and human single CYP3A4 and CYP2C9 and their canine orthologs. Procedures—Chemical inhibitors selective for human CYP enzymes and anti-CYP antibodies were incubated with racemic ketamine and liver microsomes or specific CYPs. Ketamine N-demethylation to norketamine was determined via enantioselective capillary electrophoresis. Results—The general CYP inhibitor 1-aminobenzotriazole almost completely blocked ketamine metabolism in human and canine liver microsomes but not in equine microsomes. Chemical inhibition of norketamine formation was dependent on inhibitor concentration in most circumstances. For all 3 species, inhibitors of CYP3A4, CYP2A6, CYP2C19, CYP2B6, and CYP2C9 diminished N-demethylation of ketamine. Anti-CYP3A4, anti-CYP2C9, and anti-CYP2B6 antibodies also inhibited ketamine N-demethylation. Chemical inhibition was strongest with inhibitors of CYP2A6 and CYP2C19 in canine and equine microsomes and with the CYP3A4 inhibitor in human microsomes. No significant contribution of CYP2D6 to ketamine biotransformation was observed. Although the human CYP2C9 inhibitor blocked ketamine N-demethylation completely in the canine ortholog CYP2C21, a strong inhibition was also obtained by the chemical inhibitors of CYP2C19 and CYP2B6. Ketamine N-demethylation was stereoselective in single human CYP3A4 and canine CYP2C21 enzymes. Conclusions and Clinical Relevance—Human-specific inhibitors of CYP2A6, CYP2C19, CYP3A4, CYP2B6, and CYP2C9 diminished ketamine N-demethylation in dogs and horses. To address drug-drug interactions in these animal species, investigations with single CYPs are needed.

Objective—To evaluate and compare circulating concentrations of islet amyloid polypeptide (IAPP), insulin, and glucose in nondiabetic cats classified by body condition score (BCS) and in cats with naturally occurring diabetes mellitus. Animals—109 (82 nondiabetic, 21 nonketoacidotic diabetic, and 6 ketoacidotic diabetic) cats. rocedures—Cats were examined and BCSs were assessed on a scale of 1 to 9. After food was withheld for 12 hours, blood was collected and plasma concentrations of IAPP and serum concentrations of insulin and glucose were measured. Differences in these values were evaluated among nondiabetic cats grouped according to BCS and in diabetic cats grouped as ketoacidotic or nonketoacidotic on the basis of clinicopathologic findings. Correlations were determined among variables. Results—In nondiabetic cats, BCS was significantly and positively correlated with circulating IAPP and insulin concentrations. Mean plasma IAPP concentrations were significantly different between cats with BCSs of 5 and 7, and mean serum insulin concentrations were significantly different between cats with BCSs of 5 and 8. Serum glucose concentrations were not significantly different among nondiabetic cats. Mean IAPP concentrations were similar between nonketoacidotic diabetic cats and nondiabetic cats with BCSs of 8 or 9. Mean IAPP concentrations were significantly reduced in ketoacidotic diabetic cats, compared with those of nondiabetic cats with BCSs of 6 through 8 and of nonketoacidotic diabetic cats. Conclusions and Clinical Relevance—Results indicated that increased BCS (a measure of obesity) is associated with increased circulating concentrations of IAPP and insulin in nondiabetic cats.

Objective—To evaluate effects of transplantation of bone marrow stromal cells (BMSCs) into the CSF for the treatment of chronic spinal cord injury in dogs that had not responded by 1 month after decompressive surgery. Animals—23 dogs. Procedures—Dogs with paraplegia and loss of nociception in the pelvic limbs for at least 1 month after decompressive surgery were assigned to transplantation or control groups. Dogs in the transplantation group received BMSCs injected into the CSF 1 to 3 months after decompressive surgery. Dogs in the control group did not receive additional treatments. Improvements in gait, proprioceptive positioning, and nociception were evaluated by use of the Texas Spinal Cord Injury Scale for ≥ 6 months after BMSC transplantation. Results—6 of 10 dogs in the transplantation group regained the ability to walk, whereas only 2 of 13 dogs in the control group regained the ability to walk. Scores for the Texas Spinal Cord Injury Scale in the transplantation group were significantly higher than scores in the control group at the endpoint of the study (6 months after BMSC transplantation or after decompressive surgery for the transplantation and control groups, respectively). Only 1 dog (transplantation group) recovered nociception. All dogs from both groups had fecal and urinary incontinence. No complications were observed in relation to BMSC transplantation. Conclusions and Clinical Relevance—Injection of BMSCs into the CSF caused no complications and could have beneficial effects on pelvic limb locomotion in dogs with chronic spinal cord injuries.

Objective—To determine selected cardiopulmonary values and baroreceptor response in conscious green iguanas (Iguana iguana) and to evaluate the use of blood gas analysis and pulse oximetry in this species. Animals—15 healthy juvenile green iguanas. Procedures—Baseline cardiopulmonary values were determined in 15 conscious iguanas breathing room air. Effects of 100% O2 inspiration were also measured (n = 6), and the baroreceptor reflex was characterized by exponential sigmoidal curve fitting analysis. Results—Conscious iguanas had a mean ± SD resting heart rate of 52 ± 8 beats/min, respiratory rate of 28 ± 6 breaths/min, and systolic, mean, and diastolic arterial blood pressures of 69 ± 10 mm Hg, 62 ± 12 mm Hg, and 56 ± 13 mm Hg, respectively. Mean arterial pH at 37°C was 7.29 ± 0.11, Pao2 was 81 ± 10 mm Hg, and Paco2 was 42 ± 9 mm Hg; corrected for a body temperature of 30°C, mean arterial pH at 37°C was 7.382 ±0.12, Pao2 was 54 ± 15 mm Hg, and Paco2 was 32 ± 7 mm Hg. Inspiration of 100% O2 did not change heart and respiratory rates but increased Pao2 to 486 ± 105 mm Hg (corrected value, 437 ± 96 mm Hg). A baroreceptor reflex was evident, with mean heart rates ranging from 30 ± 3 beats/min to 63 ± 5 beats/min and mean arterial blood pressures ranging from 42 ± 3 mm Hg to 58 ± 3 mm Hg. Conclusions and Clinical Relevance—This study provided needed information on cardiopulmonary values in healthy green iguanas, the application and limitation of arterial and venous blood gas analysis, and the accuracy of pulse oximetry.

Objective--To characterize the temporal and spatial distribution and reproductive ratio of vesicular stomatitis (VS) outbreaks reported in Mexico in 2008. Procedures--The Poisson model of the space-time scan statistic was used to identify periods and geographical locations at highest risk for VS in Mexico in 2008. The herd reproductive ratio (Rh) of the epidemic was computed by use of the doubling-time method. Results--1 significant space-time cluster of VS was detected in the state of Michoacan from September 4 through December 10, 2008. The temporal extent of the VS outbreaks and the value and pattern of decrease of the Rh were different in the endemic zone of Tabasco and Chiapas, compared with findings in the region included in the space-time cluster. Conclusions and Clinical Relevance--The large number of VS outbreaks reported in Mexico in 2008 was associated with the spread of the disease from the endemic zone in southern Mexico to areas sporadically affected by the disease. Results suggested that implementation of a surveillance system in the endemic zone of Mexico aimed at early detection of changes in the value of Rh and space-time clustering of the disease could help predict occurrence of future VS outbreaks originating from this endemic zone. This information will help prevent VS spread into regions of Mexico and neighboring countries that are only sporadically affected by the disease.

Objective--To investigate the roles of transforming growth factor-β (TGF-β) isoforms and matrix metalloproteinases (MMPs) in development of chronic mitral valvular disease (CMVD) in dogs. Sample Population--12 mitral valve leaflets collected from cadavers of 5 clinically normal dogs and from 7 dogs with CMVD. Procedures--Expression of TGF-β isoforms 1, 2, and 3; MMPs 1, 2, 3, and 9; TGF-β receptor II (TβR-II); and α smooth muscle actin (αSMA) in mitral valves of dogs with CMVD was compared with that in mitral valves from clinically normal dogs. Additionally, responses of valvular interstitial cells (VICs) to TGF-β3, MMP-3, and angiotensin-converting enzyme inhibitor (ACEI) as a suppressor of TGF-β3 were examined in vitro. Results--Expression of TGF-β3, TβR-II, αSMA, and MMP-3 was only detected in mitral valves of dogs with CMVD. Concentrations of αSMA and proteoglycans in cultured VICs were significantly increased following incubation with TGF-β3; treatment with MMP-3 resulted in increased amounts of active and total TGF-β3, and total TGF-β3 in VICs was significantly decreased by incubation with ACEI. Conclusions and Clinical Relevance--Findings suggested that increased TGF-β3 and MMP-3 contribute to the pathogenesis of valvular degeneration associated with CMVD. In addition, it is possible that the use of ACEI could effectively block pathological alterations in VICs associated with CMVD in vitro. Impact on Human Medicine--CMVD is associated with primary mitral valve prolapse and Marfan syndrome in humans. Results of the study reported here will help to elucidate the molecular mechanisms of CMVD in dogs and humans.

Objective—To describe daily, hourly, and animal-to-animal effects on lying behavior in steers. Animals—25 crossbred beef steers. Procedures—Wireless accelerometers were used to record behavioral data for cattle housed in a drylot cattle research facility during two 20-day periods (winter 2007 [n = 10 steers] and spring 2008 [15]). Behavioral data were categorized into lying, standing, and walking behaviors for each time point recorded. Logistic regression models were used to determine potential associations between the percentage of time spent lying and several factors, including time (hour) of day, day of trial, and steer. Results—Lying behavior was significantly associated with hour of day, and a distinct circadian rhythm was identified. Steers spent > 55% of the time between 8:00 pm and 4:00 am lying and were most active (<30% lying behavior) during feeding periods (6:00 am to 7:00 am and 4:00 pm to 5:00 pm). Model-adjusted mean percentage of time spent lying was significantly associated with study day and was between 45% and 55% on most (27/40 [67.5%]) days. Lying behavior varied significantly among steers, and mean ± SD percentage of time spent lying ranged from 28.9 ± 6.1 % to 66.1 ± 6.6%. Conclusions and Clinical Relevance—Cattle had distinct circadian rhythm patterns for lying behavior, and percentage of time spent lying varied by day and among steers. Researchers need to account for factors that affect lying patterns of cattle (ie, time of day, day of trial, and individual animal) when performing research with behavioral outcomes.

Objective—To evaluate whether guaifenesin can prevent adverse anesthetic induction events caused by propofol and whether a guaifenesin-propofol induction combination has brief cardiovascular effects commensurate with rapid drug washout. Animals—8 healthy adult horses. Procedures—Guaifenesin was administered IV for 3 minutes followed by IV injection of a bolus of propofol (2 mg/kg). Additional propofol was administered if purposeful movement was detected. Anesthesia was maintained for 2 hours with isoflurane or sevoflurane at 1.2 times the minimum alveolar concentration with controlled normocapnic ventilation. Normotension was maintained via a dobutamine infusion. Plasma concentrations of propofol and guaifenesin were measured every 30 minutes. Results—Mean ± SD guaifenesin and propofol doses inducing anesthesia in half of the horses were 73 ± 18 mg/kg and 2.2 ± 0.3 mg/kg, respectively. No adverse anesthetic induction events were observed. By 70 minutes, there was no significant temporal change in the dobutamine infusion rate required to maintain normotension for horses anesthetized with isoflurane or sevoflurane. Mean plasma guaifenesin concentrations were 122 ± 30µM, 101 ± 33µM, 93 ± 28µM, and 80 ± 24µM at 30, 60, 90, and 120 minutes after anesthetic induction, respectively. All plasma propofol concentrations were below the limit of quantitation. Conclusions and Clinical Relevance—Guaifenesin prevented adverse anesthetic induction events caused by propofol. Guaifenesin (90 mg/kg) followed by propofol (3 mg/kg) should be sufficient to immobilize > 99% of calm healthy adult horses. Anesthetic drug washout was rapid, and there was no change in inotrope requirements after anesthesia for 70 minutes.

Objective—To compare the toxic effects of a Delphinium occidentale chemotype containing -(methylsuccinimido) anthranoyllycoctonine (MSAL)—type alkaloids and a D occidentale chemotype lacking MSAL-type alkaloids in mice and cattle. Animals—225 male Swiss Webster mice and 11 Black Angus steers. Procedures—4 collections of larkspur containing MSAL-type alkaloids and 4 collections of larkspur lacking MSAL-type alkaloids were used. From each collection, total alkaloid extracts (0.05 to 0.20 mL) were administered via tail-vein injection in 27 to 29 mice. Dried, finely ground plant material from 1 collection with and 1 collection without MSAL-type alkaloids (doses equivalent to 37.6 mg of total alkaloids/kg) were each administered to 8 cattle via oral gavage in a crossover experiment; 3 cattle received a single dose equivalent to 150.4 mg of total alkaloids/kg (no MSAL-type alkaloids). In mice, clinical effects were monitored; in cattle, heart rate was monitored before (baseline) and 24 hours after treatment. At the 24-hour time point, cattle were exercised as a measure of muscle weakness. Results—In mice, mean LD50 associated with alkaloid extracts prepared from plants that did or did not contain MSAL-type alkaloids was 2.3 and 54.2 mg/kg, respectively. In cattle at 24 hours after treatment, plant material containing MSAL-type alkaloids significantly increased heart rate from baseline and was associated with exercise-induced collapse; plant material lacking MSAL-type alkaloids had no similar effects. Conclusions and Clinical Relevance—Taxonomic classification of D occidentale alone was not a good indicator of the toxic risk to grazing cattle.