Objective—To compare results of single-point kinetic gait analysis (peak and impulse) with those of complete gait waveform analysis.
Animals—15 healthy adult mixed-breed dogs.
Procedures—Dogs were trotted across 2 force platforms (velocity, 1.7 to 2.1 m/s; acceleration and deceleration, 0.5 m/s2). Five valid trials were recorded on each testing day. Testing days 1 and 2 were separated by 1 week, as were days 3 and 4. Testing days 1 and 2 were separated from days 3 and 4 by 1 year. A paired t test was performed to evaluate interday and interyear differences for vertical and craniocaudal propulsion peak forces and impulses. Vertical and craniocaudal propulsion force-time waveforms were similarly compared by use of generalized indicator function analysis (GIFA).
Results—Vertical and craniocaudal propulsion peak forces and impulses did not differ significantly between days 1 and 2 or days 3 and 4. When data were compared between years, no significant differences were found for vertical impulse and craniocaudal propulsion peak force and impulse, but differences were detected for vertical peak force. The GIFA of the vertical and craniocaudal force-time waveforms identified significant interday and interyear differences. These results were identical for both hind limbs.
Conclusions and Clinical Relevance—Findings indicated that when comparing kinetic data overtime, additional insight may be gleaned from GIFA of the complete waveform, particularly when subtle waveform differences are present.
Objective—To evaluate in vivo activityin dogs of
meloxicam or aspirin, previously shown in vitro to be a
selective cyclooxygenase-2 (COX-2) inhibitor (COX-1
sparing drug), or a nonselective COX inhibitor, respectively.
Animals—12 male dogs with unilateral osteoarthritis
of the stifle joint.
Procedure—Each dog was treated in a crossover
design with aspirin or meloxicam for 21 days.
Prostaglandin E2 (PGE2) concentrations were measured
at days 0 (baseline), 7, and 21 of each treatment
period in lipopolysaccharide (LPS)-stimulated blood,
synovial fluid collected by arthrocentesis, and endoscopic
gastric mucosal biopsy specimens.
Thromboxane B2 (TXB2) was evaluated in blood on
days 0, 7, and 21 of each treatment period.
Results—Aspirin administration significantly suppressed
PGE2 concentrations in blood, gastric
mucosa, synovial fluid, and suppressed TXB2 concentration
in blood at days 7 and 21. Meloxicam
administration significantly suppressed PGE2 concentrations
in blood and synovial fluid at days 7 and
21, but had no effect on concentrations of TXB2 in
blood or PGE2 in gastric mucosa. Suppression of
LPS-stimulated PGE2 concentrations in blood and
synovial fluid by aspirin and meloxicam administration
is consistent with activity against the COX-2
isoenzyme. Suppression of concentrations of PGE2
in the gastric mucosa and TXB2 in blood by aspirin
administration is consistent with activity against
COX-1. Meloxicam, in contrast, had a minimal effect
on functions mediated by COX-1.
Conclusions and Clinical Relevance—Meloxicam
acts in vivo in dogs as a COX-1 sparing drug on target
tissues by sparing gastric PGE2 synthesis while
retaining antiprostaglandin effects within inflamed
joints. (Am J Vet Res 2002;63:1527–1531)
Objective—To evaluate the effects of firocoxib, meloxicam, and tepoxalin administration in healthy cats by measuring the ability of stimulated tissues to synthesize eicosanoids ex vivo.
Animals—8 healthy adult male cats.
Procedures—In a blinded, randomized, crossover study design, cats were treated with firocoxib (1 mg/kg, PO, q 24 h), meloxicam (0.05 mg/kg, PO, q 24 h), tepoxalin (5.0 mg/kg, PO, q 12 h), or a placebo for 8 days. Blood samples and gastric and duodenal mucosal biopsy specimens were collected on days 0 (baseline; immediately before treatment), 3, and 8 of each treatment period. Thromboxane B2 (TXB2) concentrations were measured in serum, and prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) concentrations were measured in plasma. Prostaglandin E1 (PGE1) synthesis, PGE2 synthesis, and LTB4 concentrations were measured in mucosal biopsy specimens. A 21-day minimum washout period was observed between treatments. Repeated-measures analyses were performed.
Results—Firocoxib and meloxicam administration resulted in a lower plasma PGE2 concentration than at baseline on days 3 and 8 of administration, whereas tepoxalin administration did not. Tepoxalin administration resulted in a lower serum TXB2 concentration and pyloric and duodenal PGE1 synthesis on both days, compared with baseline and placebo administration. Neither firocoxib nor meloxicam administration altered pyloric or duodenal PGE1 synthesis on either day, compared with placebo administration. Tepoxalin administration also resulted in lower pyloric mucosal LTB4 concentrations on both days, compared with baseline values.
Conclusions and Clinical Relevance—Firocoxib and meloxicam administration had no effect on cyclooxygenase-1 activity, whereas tepoxalin administration resulted in inhibition of cyclooxygenase-1 and 5-lipoxygenase. (Am J Vet Res 2010;71:1067–1073)
Objective—To determine pharmacodynamic and pharmacokinetic properties of clopidogrel and the metabolite SR 26334 in dogs.
Animals—9 mixed-breed dogs.
Procedures—8 dogs received clopidogrel (mean ± SD 1.13 ± 0.17 mg/kg, PO, q 24 h) for 3 days; 5 of these dogs subsequently received a lower dose of clopidogrel (0.5 ± 0.18 mg/kg, PO, q 24 h) for 3 days. Later, 5 dogs received clopidogrel (1.09 ± 0.12 mg/kg, PO, q 24 h) for 5 days. Blood samples were collected for optical platelet aggregometry, citrated native and platelet mapping thrombelastography (TEG), and measurement of plasma drug concentrations. Impedance aggregometry was performed on samples from 3 dogs in each 3-day treatment group.
Results—ADP-induced platelet aggregation decreased (mean ± SD 93 ± 6% and 80 ± 22% of baseline values, respectively) after 72 hours in dogs in both 3-day treatment groups; duration of effect ranged from > 3 to > 7 days. Platelet mapping TEG and impedance aggregometry yielded similar results. Citrated native TEG was not different among groups. Clopidogrel was not detected in any samples; in dogs given 1.13 ± 0.17 mg/kg, maximum concentration of SR 26334 (mean ± SD, 0.206 ± 0.2 μg/mL) was detected 1 hour after administration.
Conclusions and Clinical Relevance—Clopidogrel inhibited ADP-induced platelet aggregation in healthy dogs and may be a viable antiplatelet agent for use in dogs.
Impact for Human Medicine—Pharmacodynamic effects of clopidogrel in dogs were similar to effects reported in humans; clopidogrel may be useful in studies involving dogs used to investigate human disease.
Objective—To evaluate the in vivo effects of firocoxib, meloxicam, and tepoxalin on prostaglandin (PG) and leukotriene production in duodenal mucosa and other target tissues in dogs with chronic osteoarthritis (OA).
Animals—8 dogs with chronic, unilateral OA of the stifle joint.
Procedures—In a crossover design, each dog received placebo (no treatment), firocoxib, meloxicam, or tepoxalin for 7 days, followed by a 21-day washout period. On the first day of treatment (day 0; baseline) and days 2, 4, and 7, samples of whole blood, synovial fluid, and gastric and duodenal mucosae were collected. Prostaglandin E2 concentrations were measured in synovial fluid of the stifle joint and after ex vivo stimulation of whole blood samples. Synthesis of PGE1 and PGE2 was measured in samples of gastric and duodenal mucosae. Concentrations of thromboxane B2 (TxB2) were measured in whole blood samples. Leukotriene B4 (LTB4) concentrations were measured in samples of whole blood (ex vivo stimulation) and gastric and duodenal mucosae.
Results—Firocoxib, meloxicam, and tepoxalin significantly suppressed whole blood concentrations of PGE2, compared with baseline and placebo concentrations, at days 2, 4, and 7. Tepoxalin significantly suppressed serum TxB2 concentrations, compared with baseline, firocoxib, meloxicam, and placebo, at all 3 time points. Production of PGE1 and PGE2 was significantly lower in duodenal versus gastric mucosa. Tepoxalin significantly decreased rates of PGE1 and PGE2 in duodenal and gastric mucosae, compared with baseline rates.
Conclusions and Clinical Relevance—PG production was lower in the duodenum than in the stomach. Firocoxib had a COX-1–sparing effect in vivo.
Objective—To evaluate the accuracy of artificial neural networks (ANNs) for use in predicting subjective diagnostic scores of lameness with variables determined from ground reaction force (GRF) data.
Animals—21 adult mixed-breed dogs.
Procedures—The left cranial cruciate ligament of each dog was transected to induce osteoarthritis of the stifle joint as part of another study. Lameness scores were assigned and GRF data were collected 2 times before and 5 times after ligament transection. Inputs and the output for each ANN were GRF variables and a lameness score, respectively. The ANNs were developed by use of data from 14 dogs and evaluated by use of data for the remaining 7 dogs (ie, dogs not used in model development).
Results—ANN models developed with 2 preferred input variables had an overall accuracy ranging from 96% to 99% for 2 data configurations (data configuration 1 contained patterns or observations for 7 dogs, whereas data configuration 2 contained patterns or observations for 7 other dogs). When additional variables were added to the models, the highest overall accuracy ranged from 97% to 100%.
Conclusions and Clinical Relevance—ANNs provided a method for processing GRF data of dogs to accurately predict subjective diagnostic scores of lameness. Processing of GRF data via ANNs could result in a more precise evaluation of surgical and pharmacological intervention by detecting subtle lameness that could have been missed by visual analysis of GRF curves.
Objective—To quantify the 3-D kinematics and collateral ligament strain of stifle joints in cadaveric canine limbs before and after cranial cruciate ligament transection followed by total knee replacement (TKR) involving various tibial plateau angles and spacer thicknesses.
Sample—6 hemi-pelvises collected from clinically normal nonchondrodystrophic dogs (weight range, 25 to 35 kg).
Procedures—Hemi-pelvises were mounted on a modified Oxford knee rig that allowed 6 degrees of freedom of the stifle joint but prevented mechanical movement of the hip and tarsal joints. Kinematics and collateral ligament strain were measured continuously while stifle joints were flexed. Data were again collected after cranial cruciate ligament transection and TKR with combinations of 3 plateau angles (0°, 4°, and 8°) and spacer thicknesses (5, 7, and 9 mm).
Results—Presurgical (ie, normal) stifle joint rotations were comparable to those previously documented for live dogs. After TKR, kinematics recorded for the 8°, 5-mm implant most closely resembled those of unaltered stifle joints. Decreasing the plateau angle and increasing spacer thickness altered stifle joint adduction, internal rotation, and medial translation. Medial collateral ligament strain was minimal in unaltered stifle joints and was unaffected by TKR. Lateral collateral ligament strain decreased with steeper plateau angles but returned to a presurgical level at the flattest plateau angle.
Conclusions and Clinical Relevance—Among the constructs tested, greatest normalization of canine stifle joint kinematics in vitro was achieved with the steepest plateau angle paired with the thinnest spacer. Furthermore, results indicated that strain to the collateral ligaments was not negatively affected by TKR.
To investigate the ability of a proprietary antagonist of E-type prostanoid receptor (EP) 4, grapiprant, and carprofen to attenuate lameness attributable to urate-induced synovitis in dogs.
5 purpose-bred hound-cross dogs.
A blinded, 3-way crossover study was performed. Dogs received each of 3 treatments (L-766, a proprietary antagonist of EP4; 4.0 mg/kg), grapiprant (an antagonist of EP4; 2.0 mg/kg), and carprofen (4.4 mg/kg); dogs received 4 doses of each treatment (14 and 2 hours before and 22 and 46 hours after urate injection). Synovitis was induced by intra-articular injection of sodium urate. Measurements (vertical ground reaction forces and clinical lameness scores) were obtained immediately before (0 hours; baseline) and 6, 12, 24, 36, and 48 hours after sodium urate injection. All data were analyzed with repeated-measures ANOVA.
Lameness scores at 6 hours were significantly higher than baseline lameness scores for all treatments. Lameness scores for the grapiprant treatment remained significantly higher at 12 and 24 hours, compared with baseline lameness scores. Lameness scores for the carprofen treatment were significantly lower than lameness scores for the grapiprant treatment at 6, 12, and 24 hours. Analysis of peak vertical force and vertical impulse data revealed a pattern similar to that for lameness scores. Treatment with L-766 resulted in a significantly higher vertical impulse at 48 hours than did treatment with carprofen or grapiprant.
CONCLUSIONS AND CLINICAL RELEVANCE
In these dogs, carprofen was the most effective treatment for attenuating lameness induced by injection of sodium urate, and grapiprant was the least effective treatment.
Objective—To determine whether 1% diclofenac
liposomal suspension (DLS) ointment would be
absorbed transdermally and attenuate experimentally
induced subcutaneous inflammation in horses.
Animals—7 healthy adult horses
Procedure—Inflammation was produced by injecting
1% sterile carrageenan into subcutaneously implanted
tissue cages 8 hours before (time –8) and at the
time of application of test ointment. A crossover
design was used. Horses received 1 of 2 treatments
(topically administered control or DLS ointments) during
48 hours of carrageenan-induced subcutaneous
inflammation. A single application of test ointment
(7.2 g) was applied over each tissue cage (time 0).
Samples of transudate and blood were collected at
–8, 0, 6, 12, 18, 24, 30, 36, and 48 hours. Plasma and
transudate diclofenac concentrations were determined
by use of high-performance liquid chromatography.
Transudate concentrations of prostaglandin E2
(PGE2) were determined with a competitive enzyme
Results—DLS was absorbed transdermally. The highest
concentration (mean ± SEM, 76.2 ± 29 ng/mL)
was detectable in tissue-cage fluid within 18 hours
after application. Minimal concentrations of diclofenac
were detectable in plasma. Application of DLS significantly
decreased transudate concentrations of PGE2
at 6 and 30 hours. Decreases in PGE2 concentration
were observed in the DLS group at all collection
Conclusions and Clinical Relevance—A single topical
application of DLS resulted in concentrations of
diclofenac in transudate within 6 hours and significantly
attenuated carrageenan-induced local production
of PGE2. Results of this study suggest that DLS
is readily absorbed transdermally and may be efficacious
for reducing subcutaneous inflammation in
horses. ( Am J Vet Res 2004;65:271–276)