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.

Objective--To characterize the localization, visible extent (ie, measurement of selected dimensions), and appearance of the liver, caudal vena cava, portal vein, and gallbladder during ultrasonography in healthy goats. Animals--27 female Saanen goats. Procedures--A 5.0-MHz linear transducer was used to ultrasonographically examine the localization, visible extent of various dimensions, and appearance of the liver, caudal vena cava, portal vein, and gallbladder from the right side of each goat. Results--Images of the liver were obtained in all goats. The dorsal margin of the liver extended in a cranioventral to caudodorsal direction parallel to the caudal margin of the lungs. The greatest visible extent of the liver was evident at the seventh and eighth intercostal spaces (mean value, 15.9 cm), and width was evident at the 10th intercostal space (mean value, 5.2 cm). The caudal vena cava had a triangular shape on cross section; the maximum width in cross section, circumference, and surface area ranged from 1.2 to 1.8 cm, 4.8 to 5.2 cm, and 0.8 to 1.1 cm2, respectively. The portal vein was round on cross section (diameter, 0.8 to 1.7 cm) with stellate ramifications into the liver parenchyma. The gallbladder was pear-shaped and variable in size; it extended beyond the ventral margin of the liver to a variable degree depending on the amount of bile. Conclusions and Clinical Relevance--Results provided information regarding the ultrasonographic appearance of the liver, caudal vena cava, portal vein, and gallbladder in healthy goats; these data may be useful during examination of goats with suspected liver disease.

Objective—To evaluate the ability of industrial polystyrene foam insulation pads to redistribute loads placed on clinically normal weight-bearing structures of the foot and shift the location of the center of pressure palmarly in horses. Animals—25 nonlame mature horses. Procedures—Both forefeet from each horse were evaluated. Center of pressure data and solar load distribution patterns were recorded during a 5-second trial by use of a commercial pressure measurement system prior to placement of foam sole support and at 0, 6, 12, 24, and 48 hours after placement. Total contact surface area, contact pressure, peak contact pressure, and center of pressure positions were compared by use of a linear mixed model with repeated measurements. Results—Total contact surface area was increased significantly at all time points, whereas contact pressure and peak contact pressure were significantly decreased at all time points following application of foam sole supports. Immediately following application of sole support, the position of the center of pressure was significantly moved cranially. However, by 48 hours, the center of pressure was significantly positioned more palmarly than prior to application of the foam supports. Conclusions and Clinical Relevance—Results indicated that the use of foam sole supports may be an effective, economical, and immediate treatment for acute laminitis.

Objective—To evaluate effects of long-term administration of carprofen on healing of a tibial osteotomy in dogs. Animals—12 healthy female Beagles. Procedures—A mid-diaphyseal transverse osteotomy (stabilized with an intramedullary pin) of the right tibia was performed in each dog. The carprofen group (n = 6 dogs) received carprofen (2.2 mg/kg, PO, q 12 h) for 120 days; the control group (6) received no treatment. Bone healing and change in callus area were assessed radiographically over time. Dogs were euthanized 120 days after surgery, and tibiae were evaluated biomechanically and histologically. Results—The osteotomy line was not evident in the control group on radiographs obtained 120 days after surgery. In contrast, the osteotomy line was still evident in the carprofen group. Callus area was significantly less in the carprofen group, compared with the area in the control group, at 20, 30, and 60 days after surgery. At 120 days after surgery, stiffness, elastic modulus, and flexural rigidity in the carprofen group were significantly lower than corresponding values in the control group. Furthermore, histologic evaluation revealed that the cartilage area within the callus in the carprofen group was significantly greater than that in the control group. Conclusions and Clinical Relevance—Long-term administration of carprofen appeared to inhibit bone healing in dogs that underwent tibial osteotomy. We recommend caution for carprofen administration when treating fractures that have delays in healing associated with a reduction in osteogenesis as well as fractures associated with diseases that predispose animals to delays of osseous repair.

Objective-To determine plasma concentrations and behavioral, antinociceptive, and physiologic effects of methadone administered via IV and oral transmucosal (OTM) routes in cats. Animals-8 healthy adult cats. Procedures-Methadone was administered via IV (0.3 mg/kg) and OTM (0.6 mg/kg) routes to each cat in a balanced crossover design. On the days of drug administration, jugular catheters were placed in all cats under anesthesia; a cephalic catheter was also placed in cats that received methadone IV. Baseline measurements were obtained greater than 90 minutes after extubation, and methadone was administered via the predetermined route. Heart and respiratory rates were measured; sedation, behavior, and antinociception were evaluated, and blood samples were collected for methadone concentration analysis at predetermined intervals for 24 hours after methadone administration. Data were summarized and evaluated statistically. Results-Plasma concentrations of methadone were detected rapidly after administration via either route. Peak concentration was detected 2 hours after OTM administration and 10 minutes after IV administration. Mean +/- SD peak concentration was lower after OTM administration (81.2 +/- 14.5 ng/mL) than after IV administration (112.9 +/- 28.5 ng/mL). Sedation was greater and lasted longer after OTM administration. Antinociceptive effects were detected 10 minutes after administration in both groups; these persisted greater than 2 hours after IV administration and greater than 4 hours after OTM administration. Conclusions and Clinical Relevance-Despite lower mean peak plasma concentrations, duration of antinociceptive effects of methadone was longer after OTM administration than after IV administration. Methadone administered via either route may be useful for perioperative pain management in cats.

Objective-To assess the accuracy of isoflurane, halothane, and sevoflurane vaporizers during high oxygen flow and at maximum dial settings at room temperature and to test sevoflurane vaporizers similarly during heating and at low-fill states. Sample-5 isoflurane, 5 halothane, and 5 sevoflurane vaporizers. Procedures-Vaporizers were tested at an oxygen flow of 10 L/min and maximum dial settings for 15 minutes under various conditions. All 3 vaporizer types were filled and tested at room temperature (21 degrees to 23 degrees C). Filled sevoflurane vaporizers were wrapped with circulating hot water (42 degrees C) blankets for 2 hours and tested similarly, and near-empty sevoflurane vaporizers were tested similarly at room temperature. During each 15-minute test period, anesthetic agent concentration was measured at the common gas outlet with a portable refractometer and temperature of the vaporizer wall was measured with a thermistor. Results-For each vaporizer type, anesthetic agent concentrations and vaporizer wall temperatures decreased during the 15-minute test period. Accuracy of isoflurane and halothane vaporizers remained within the recommended 20% (plus or minus) deviation from dial settings. Heated and room-temperature sevoflurane vaporizers were accurate to within 23% and 11.7% (plus or minus) of dial settings, respectively. Sevoflurane vaporizers at low-fill states performed similarly to vaporizers at full-fill states. Conclusions and Clinical Relevance-Under these study conditions, the isoflurane and halothane vaporizer models tested were accurate but the sevoflurane vaporizers were not. Sevoflurane vaporizer accuracy was not affected by fill state but may be improved with vaporizer heating; measurements of inspired anesthetic agent concentrations should be obtained during the use of heated vaporizers.

Objective—To determine the effect of differences in structural and mechanical tendon properties on functionality of the passive stay apparatus in horses. Sample—5 forelimbs each from nondwarf Friesians, dwarf Friesians, and ponies. Procedures—Harvested forelimbs were loaded to test the passive stay apparatus. Tendons that stabilize the distal portion of the limb (superficial digital flexor tendon, deep digital flexor tendon, and tendo interosseus [suspensory ligament]) were isolated, and force-elongation data were obtained. Bone lengths, initial tendon lengths, and initial tendon cross-sectional areas were measured, and Young moduli were calculated. A model was used to determine whether joint angles could be explained by these 4 factors only. Results—Dwarf limbs were unable to stand passively under loading because tendons that prevent overextension of the distal limb joints were too long and compliant to prevent over-extension. Tendon properties of limbs of nondwarf Friesians appeared to be intermediate between those of ponies and dwarf Friesians. Conclusions and Clinical Relevance—Dysfunction of the passive stay apparatus in dwarf Friesians could be related to differences in structural and material properties of the tendons that result in hyperextension of the joints under loading. Nondwarf Friesians had intermediate tendon properties, which might be a breed-specific variation. Results indicated that certain tendon properties were associated with load failure of the stay apparatus and provided additional information about the functionality and requirements of the passive stay apparatus.