Objective—To describe changes in vertical ground
reaction forces (GRF) over 48 months in dogs with
osteoarthritis (OA) of the stifle joint induced by transection
of a cranial cruciate ligament (CCL).
Animals—12 clinically normal adult dogs.
Procedure—Vertical GRF (eg, peak force and
impulse) were determined prior to and 1, 2, 3, 6, 10,
and 12 months after transection of the right CCL. In 7
dogs, data were also collected 24, 32, 38, 42, and 48
months after transection.
Results—Vertical peak force and impulse were significantly
decreased in the right hind limb at all times
after transection, compared with baseline values.
From 10 through 48 months after transection, vertical
GRF remained essentially static. Ground reaction
forces in the unoperated (left) hind limb also changed
significantly during the study. Left vertical impulse significantly
increased 3 months after transection,
whereas at 24, 38, 42, and 48 months after transection,
left vertical peak force was significantly
decreased, compared with the baseline value .Mean
intradog coefficients of variation (CV) for peak vertical
force and impulse ranged from 7.38 and 9.32, respectively,
1 month after transection to 1.96 and 2.76,
respectively, at 42 months.
Conclusions and Clinical Relevance—Vertical GRF
in the affected hind limb equilibrated approximately 10
months after CCL transection. Prior to this, force
transmission across the affected stifle joint changed
significantly over time. Intradog CV were small, indicating
that GRF may be an appropriate outcome measurement
for evaluation of OA development induced
by CCL transection in dogs. (Am J Vet Res 2001;62:1207–1211)
To develop a 3-D kinematic model to measure truncal motion in dogs and assess changes in truncal motion in dogs when wearing each of 2 service vests.
5 adult mixed-breed dogs.
27 reflective markers were placed on the pelvis, trunk, and scapula of each dog. Six infrared cameras were placed around a treadmill to track the location of the markers within a calibrated space. Dogs were recorded during walking and trotting on the treadmill. Local and global coordinate systems were established, and a segmental rigid-body model of the trunk was created. Dogs were then recorded while wearing a custom vest and an adjustable vest during walking and trotting on the treadmill. Range of motion of the trunk when dogs were and were not wearing vests was compared by repeated-measures ANOVA.
An anatomic coordinate system was established by use of markers located at T1, T13, and the xiphoid process. Range of motion of the trunk during a gait cycle did not differ significantly regardless of the day of the test for both walking and trotting gaits. Trunk motion of dogs when walking and trotting was significantly reduced when dogs were wearing a vest, compared with trunk motion when not wearing a vest.
CONCLUSIONS AND CLINICAL RELEVANCE
A 3-D kinematic model for measuring truncal rotation was developed. Results indicated measurable differences in the gait of dogs when wearing each of the 2 service vests, compared with the gait when not wearing a vest.
Objective—To evaluate cyclooxygenase (COX) selectivity
of several nonsteroidal anti-inflammatory drugs
(NSAID) in canine blood in vitro.
Animals—11 healthy adult male hound crosses.
Procedure—9 NSAID were studied at 5 concentrations.
Thromboxane B2 (TxB2) was assayed as a
measure of COX-1 activity in clotted blood.
Prostaglandin E2 (PGE2) was assayed as a measure
of COX-2 activity in heparinized, lipopolysaccharide
(LPS)-stimulated blood. All assays were competitive
ELISA tests. Cyclooxygenase selectivity was
expressed as a ratio of the concentration of an
NSAID that inhibited 50% of the activity (IC50) of
COX-1 to the IC50 of COX-2. A separate ratio of the
concentration that inhibited 80% of COX activity
(IC80) was also determined. A ratio of
< 1.0 indicated selectivity for COX-1, whereas a
ratio of > 1.0 indicated COX-2 selectivity.
Results—Ketoprofen, aspirin, and etodolac were
COX-1 selective. Piroxicam, meloxicam, and carprofen
had COX-2 selectivity. The IC50 and IC80 values
were similar for most NSAID.
Conclusion and Clinical Relevance—This methodology provides repeatable
data from individual dogs and is comparable to results
of previous in vitro and ex vivo models. Findings are
also consistent with those of canine studies performed
in vivo, suggesting that this is a viable in vitro
assessment of the COX selectivity of NSAID in dogs.
(Am J Vet Res 2002;63:91–94)
Objective—To evaluate in vivo activity of carprofen,
deracoxib, and etodolac on prostanoid production in
several target tissues in dogs with chronic
Animals—8 dogs with chronic unilateral osteoarthritis
of the stifle joint.
Procedure—Each dog received carprofen, deracoxib,
or etodolac for 10 days with a 30- to 60-day washout
period between treatments. On days 0, 3, and 10,
prostaglandin (PG) E2 concentrations were measured
in lipopolysaccharide-stimulated blood, synovial fluid,
and gastric mucosal biopsy specimens; PGE1 concentrations
were measured in gastric mucosal biopsy
specimens; and thromboxane B2 (TXB2) was evaluated
Results—Carprofen and deracoxib significantly suppressed
PGE2 concentrations in blood at days 3 and
10, compared with baseline, whereas etodolac did
not. None of the drugs significantly suppressed TXB2
concentrations in blood or gastric PGE1 synthesis at
any time point. All 3 drugs significantly decreased
gastric synthesis of PGE2 at day 3 but not day 10 of
each treatment period. All 3 drugs decreased synovial
fluid PGE2 concentrations in the affected and unaffected
stifle joints at days 3 and 10.
Conclusions and Clinical Relevance—Results indicate
that carprofen and deracoxib act in vivo on target
tissues as COX-1–sparing drugs by sparing gastric
PGE1 and PGE2 synthesis and production of TXB2 by
platelets. Etodolac also appears to be COX-1 sparing
but may have variable effects on COX-2 depending on
the tissue. In gastric mucosa and synovial fluid, there
were no significant differences in PG production
between compounds at recommended concentrations.
(Am J Vet Res 2005;66:812–817)
Objective—To evaluate a 3-D kinematic model of the hind limb developed by use of a joint coordinate system in dogs.
Animals—6 clinically normal adult mixed-breed dogs.
Procedures—17 retroreflective markers were affixed to the skin on the right hind limb of each dog. Eight infrared cameras were arranged around a gait platform to record marker locations as dogs were recorded moving through the calibrated space 5 times during a walk and trot at velocities of 0.9 to 1.2 m/s and 1.7 to 2.1 m/s, respectively. Local and global coordinate systems were established, and a segmental rigid-body model of the canine hind limb was produced. Dynamic 3-D joint kinematic measurements were collected for the hip, stifle, and tarsal joints.
Results—Sagittal (flexion-extension), transverse (internal-external rotation), and frontal (abduction-adduction) plane kinematic measurements were acquired during each trial for the hip, stifle, and tarsal joints.
Conclusions and Clinical Relevance—The joint coordinate system allowed acquisition of 3-D kinematic measurements of the hip, stifle, and tarsal joints of the canine hind limb. Methods were described to model 3-D joint motion of the canine hind limb. (Am J Vet Res 2010;71:1118-1122)
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 in vivo effects of tepoxalin, an
inhibitor of cyclooxygenase (COX) and lipoxygenase
(LOX), on prostaglandin (PG) and leukotriene production
in osteoarthritic dogs.
Animals—7 mixed-breed adult dogs with chronic unilateral
arthritis of a stifle joint.
Procedure—Dogs were treated in accordance with a
randomized 3-way crossover design. Each dog
received an inert substance, meloxicam, or tepoxalin
for 10 days. On day 0 (baseline), 3, and 10, dogs were
anesthetized and samples of blood, stifle joint synovial
fluid, and gastric mucosa were collected.
Concentrations of PGE2 were measured in synovial
fluid and after lipopolysaccharide stimulation of whole
blood; PGE1 and PGE2 synthesis was measured in
gastric mucosa. Thromboxane B2 (TxB2) concentration
was measured in whole blood. Leukotriene B4 (LTB4)
concentration was determined in gastric mucosa and
in whole blood after ex vivo stimulation with a calcium
Results—Tepoxalin significantly decreased LTB4 concentrations
in the blood and gastric mucosa at day 10
and TxB2 concentrations in the blood and PGE2 in the
gastric mucosa and synovial fluid at days 3 and 10,
compared with baseline values. Meloxicam significantly
decreased PGE2 concentrations in the blood at
days 3 and 10 and synovial fluid at day 3. Meloxicam
also decreased PGE1 and PGE2 synthesis in the gastric
mucosa at day 3. Meloxicam did not affect LTB4
synthesis in the blood or LTB4 concentrations in the
Conclusions and Clinical Relevance—Tepoxalin has
in vivo inhibitory activity against COX-1, COX-2, and
5-LOX in dogs at the current approved recommended
dosage. (Am J Vet Res 2005;66:966–972)
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.