Objective—To compare 3 dose levels of medetomidine
and dexmedetomidine for use as premedicants
in dogs undergoing propofol-isoflurane anesthesia.
Animals—6 healthy Beagles.
Procedure—Dogs received medetomidine or
dexmedetomidine intravenously at the following dose
levels: 0.4 µg of medetomidine or 0.2 µg of
dexmedetomidine/kg of body weight (M0.4/D0.2), 4.0
µg of medetomidine or 2.0 µg of dexmedetomidine/
kg (M4/D2), and 40 µg of medetomidine or 20 µg
of dexmedetomidine/kg (M40/D20). Sedation and
analgesia were scored before induction. Anesthesia
was induced with propofol and maintained with
isoflurane. End-tidal isoflurane concentration, heart
rate, and arterial blood pressures and gases were
Results—Degrees of sedation and analgesia were
significantly affected by dose level but not drug.
Combined mean end-tidal isoflurane concentration for
all dose levels was higher in dogs that received
medetomidine, compared with dexmedetomidine.
Recovery time was significantly prolonged in dogs
treated at the M40/D20 dose level, compared with
the other dose levels. After induction, blood pressure
decreased below reference range and heart rate
increased in dogs treated at the M0.4/D0.2 dose
level, whereas blood pressure was preserved in dogs
treated at the M40/D20 dose level. However, dogs in
these latter groups developed profound bradycardia
and mild metabolic acidosis during anesthesia.
Treatment at the M4/D2 dose level resulted in more
stable cardiovascular effects, compared with the
other dose levels. In addition, PaCO2 was similar
among dose levels.
Conclusions and Clinical Relevance—Dexmedetomidine
is at least as safe and effective as medetomidine
for use as a premedicant in dogs undergoing
propofol-isoflurane anesthesia. (Am J Vet Res
Objective—To determine whether a high dose of levomedetomidine
had any pharmacologic activity or
would antagonize the sedative and analgesic effects
of dexmedetomidine in dogs.
Animals—6 healthy Beagles.
Procedure—Each dog received the following treatments
on separate days: a low dose of levomedetomidine
(10 µg/kg), IV, as a bolus, followed by continuous
infusion at a dose of 25 µg/kg/h; a high dose of
levomedetomidine (80 µg/kg), IV, as a bolus, followed
by continuous infusion at a dose of 200 µg/kg/h; and
a dose of isotonic saline (0.9% NaCl) solution, IV, as a
bolus, followed by continuous infusion (control). For
all 3 treatments, the infusion was continued for 120
minutes. After 60 minutes, a single dose of
dexmedetomidine (10 µg/kg) was administered IV.
Sedation and analgesia were scored subjectively, and
heart rate, blood pressure, respiratory rate, arterial
blood gas partial pressures, and rectal temperatures
Results—Administration of levomedetomidine did
not cause any behavioral changes. However, administration
of the higher dose of levomedetomidine
enhanced the bradycardia and reduced the sedative
and analgesic effects associated with administration
Conclusion and Clinical Relevance—Results suggest
that administration of dexmedetomidine alone
may have some cardiovascular benefits over administration
of medetomidine, which contains both
dexmedetomidine and levomedetomidine. Further
studies are needed to confirm the clinical importance
of the effects of levomedetomidine in dogs. (Am J Vet
Objective—To detect monocarboxylate transporters (MCTs) in canine RBC membranes and to determine the distribution of lactate between plasma and RBCs.
Sample population—Blood samples obtained from 6 purpose-bred Beagles.
Procedures—Monocarboxylate transporter isoforms 1, 2, 4, 6, 7, and 8 and CD147 were evaluated in canine RBCs by use of western blot analysis. Lactate influx into RBCs was measured as incorporation of radioactive lactate.
Results—2 MCT isoforms, MCT1 and MCT7, were detected in canine RBC membranes on western blot analysis, whereas anti-MCT2, anti-MCT4, anti-MCT6, and anti-MCT8 antibodies resulted in no signal. No correlation was found between the amount of MCT1 or MCT7 and lactate transport activity, but the ancillary protein CD147 that is needed for the activity of MCT1 had a positive linear correlation with the rate of lactate influx. The apparent Michaelis constant for the lactate influx in canine RBCs was 8.8 ± 0.9mM. Results of in vitro incubation studies revealed that at lactate concentrations of 5 to 15mM, equilibrium of lactate was rapidly obtained between plasma and RBCs.
Conclusions and Clinical Relevance—These results indicated that at least half of the lactate transport in canine RBCs occurs via MCT1, whereas MCT7 may be responsible for the rest, although an additional transporter was not ruled out. For practical purposes, the rapid equilibration of lactate between plasma and RBCs indicated that blood lactate concentrations may be estimated from plasma lactate concentrations.
Objective—To investigate the effects of oral administration of activated charcoal (AC) and urine alkalinization via oral administration of sodium bicarbonate on the pharmacokinetics of orally administered carprofen in dogs.
Animals—6 neutered male Beagles.
Procedures—Each dog underwent 3 experiments (6-week interval between experiments). The dogs received a single dose of carprofen (16 mg/kg) orally at the beginning of each experiment; after 30 minutes, sodium bicarbonate (40 mg/kg, PO), AC solution (2.5 g/kg, PO), or no other treatments were administered. Plasma concentrations of unchanged carprofen were determined via high-performance liquid chromatography at intervals until 48 hours after carprofen administration. Data were analyzed by use of a Student paired t test or Wilcoxon matched-pairs rank test.
Results—Compared with the control treatment, administration of AC decreased plasma carprofen concentrations (mean ± SD maximum concentration was 85.9 ± 11.9 mg/L and 58.1 ± 17.6 mg/L, and area under the time-concentration curve was 960 ± 233 mg/L•h and 373 ± 133 mg/L•h after control and AC treatment, respectively). The elimination half-life remained constant. Administration of sodium bicarbonate had no effect on plasma drug concentrations.
Conclusions and Clinical Relevance—After oral administration of carprofen in dogs, administration of AC effectively decreased maximum plasma carprofen concentration, compared with the control treatment, probably by decreasing carprofen absorption. Results suggest that AC can be used to reduce systemic carprofen absorption in dogs receiving an overdose of carprofen. Oral administration of 1 dose of sodium bicarbonate had no apparent impact on carprofen kinetics in dogs.
Objective—To compare the effects of pretreatment
with dexamethasone, physical stress (exercise), or
both on sedation and plasma hormone and glucose
concentrations in dogs treated with dexmedetomidine
Animals—6 healthy purpose-bred Beagles.
Procedure—Dogs received 4 treatments each in a
randomized order prior to IV administration of DEX (5
µg/kg). Pretreatments were as follows: (1) IV administration
of saline (0.9% NaCl) solution and no exercise
(control group); (2) IV administration of dexamethasone
(0.05 mg/kg) and no exercise (DM group);
(3) IV administration of saline solution and exercise
(EX group; 15 minutes of trotting on a treadmill at a
speed of 2 m/s); and 4) IV administration of dexamethasone
and exercise (DM+EX group).
Results—Following DEX administration, all dogs
had similar times to recumbency and sedation index
values, irrespective of pretreatment with dexamethasone
or exercise. Plasma catecholamine concentrations
decreased after DEX administration.
Compared with control group dogs, plasma cortisol
concentrations were higher in EX-group dogs prior
to DEX administration and lower in DM- and
DM+EX-group dogs following DEX administration.
Administration of DEX decreased plasma cortisol
concentration in EX-group dogs only. Plasma glucose
concentration was not influenced by exercise
or dexamethasone administration but was lower
than baseline concentrations at 30 minutes after
DEX administration and returned to baseline values
by 90 minutes. Heart and respiratory rates and rectal
temperature increased during exercise. After
DEX administration, these values decreased below
baseline values. The decrease in heart rate was of
shorter duration in dogs that underwent pretreatment
with dexamethasone, exercise, or both than
in control group dogs
Conclusions and Clinical Relevance—Pretreatment
with dexamethasone, moderate physical stress (exercise),
or both did not influence sedation or cause
adverse effects in healthy dogs treated with DEX.
(Am J Vet Res 2005;66:260–265)
Objective—To compare the perioperative stress
response in dogs administered medetomidine or acepromazine
as part of the preanesthetic medication.
Animals—42 client-owned dogs that underwent
Procedure—Each dog was randomly allocated to
receive medetomidine and butorphanol tartrate
(20 µg/kg and 0.2 mg/kg, respectively, IM) or acepromazine
maleate and butorphanol (0.05 and 0.2 mg/kg,
respectively, IM) for preanesthetic medication.
Approximately 80 minutes later, anesthesia was
induced by administration of propofol and maintained
by use of isoflurane in oxygen. Each dog was also
given carprofen before surgery and buprenorphine
after surgery. Plasma concentrations of epinephrine,
norepinephrine, cortisol, and β-endorphin were measured
at various stages during the perioperative period.
In addition, cardiovascular and clinical variables
Results—Concentrations of epinephrine, norepinephrine,
and cortisol were significantly lower for dogs
administered medetomidine. Concentrations of
β-endorphin did not differ between the 2 groups.
Heart rate was significantly lower and mean arterial
blood pressure significantly higher in dogs administered
medetomidine, compared with values for dogs
Conclusions and Clinical Relevance—Results indicate
that for preanesthetic medications, medetomidine
may offer some advantages over acepromazine
with respect to the ability to decrease perioperative
concentrations of stress-related hormones. In particular,
the ability to provide stable plasma catecholamine
concentrations may help to attenuate perioperative
activation of the sympathetic nervous system.
(Am J Vet Res 2002;63:969–975)
Objective—To evaluate perfusion of abdominal organs in healthy cats by use of contrastenhanced ultrasonography.
Animals—10 young healthy anesthetized cats.
Procedures—Contrast-enhanced ultrasonography of the liver, left kidney, pancreas, small intestine, and mesenteric lymph nodes was performed on anesthetized cats.
Results—Typical perfusion patterns were found for each of the studied organs. Differences in perfusion among organs were associated with specific physiologic features. The liver was enhanced gradually and had a more heterogeneous perfusion pattern because of its dual blood supply and close proximity to the diaphragm, compared with other organs. An obvious and significant difference in perfusion was detected between the renal cortex and medulla. No significant differences in perfusion were detected among the pancreas, small intestine, and mesenteric lymph nodes.
Conclusions and Clinical Relevance—Results indicated that contrast-enhanced ultrasonography can be used in cats to estimate organ perfusion as in other species. Observed differences in perfusion variables can be mostly explained by physiologic differences in vascularity. (Am J Vet Res 2010;71:1305–1311)
Objective—To evaluate protein expression in bronchoalveolar lavage fluid (BALF) obtained from West Highland White Terriers with idiopathic pulmonary fibrosis (IPF), dogs with chronic bronchitis, and healthy control dogs to identify potential biomarkers for IPF.
Samples—BALF samples obtained from 6 West Highland White Terriers with histologically confirmed IPF, 5 dogs with chronic bronchitis, and 4 healthy Beagles.
Procedures—Equal amounts of proteins in concentrated BALF samples were separated via 2-D differential gel electrophoresis. Proteins that were differentially expressed relative to results for healthy control dogs were identified with mass spectrometry and further verified via western blotting.
Results—Expression of 6 proteins was upregulated and that of 1 protein was downregulated in dogs with IPF or chronic bronchitis, compared with results for healthy dogs. Expression of proteins β-actin, complement C3, α-1-antitrypsin, apolipoprotein A-1, haptoglobin, and transketolase was upregulated, whereas expression of lysozyme C was downregulated.
Conclusions and Clinical Relevance—Proteomics can be used to search for biomarkers and to reveal disease-specific mechanisms. The quantitative comparison of proteomes for BALF obtained from dogs with IPF and chronic bronchitis and healthy dogs revealed similar changes for the dogs with IPF and chronic bronchitis, which suggested a common response to disease processes in otherwise different lung diseases. Specific biomarkers for IPF were not identified.
Animals—22 dogs with osteoarthritis in the hip or elbow joint.
Procedure—13 dogs received orally administered carprofen daily for 2 months, and 9 dogs received a placebo for 2 months. Dogs were weighed, and serum and urine samples were collected before initiation of treatment and 4 and 8 weeks after initiation of treatment. Serum concentrations of total protein, albumin, urea, and creatinine and serum activities of alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were measured. Urinary ALP-to-creatinine, γ-glutamyltransferase (GGT)-to-creatinine, and protein-to-creatinine ratios were calculated. Dogs were observed by owners for adverse effects.
Results—Serum protein and albumin concentrations were lower in treated dogs than in those that received placebo at 4 weeks, but not at 8 weeks. No changes were observed in serum urea or creatinine concentrations; ALP or ALT activity; or urinary ALP-to-creatinine, GGT-to-creatinine, or protein-to-creatinine ratios. Dogs' weights did not change. Severity of vomiting, diarrhea, and skin reactions did not differ between groups, but appetite was better in dogs receiving carprofen than in dogs in the placebo group.
Conclusions and Clinical Relevance—It is possible that the transient decreases in serum protein and albumin concentrations in dogs that received carprofen were caused by altered mucosal permeability of the gastrointestinal tract because no indications of renal or hepatic toxicity were observed. Carprofen appeared to be well tolerated by dogs after 2 months of administration.
To determine whether concurrent vatinoxan administration affects the antinociceptive efficacy of medetomidine in dogs at doses that provide circulating dexmedetomidine concentrations similar to those produced by medetomidine alone.
8 healthy Beagles.
Dogs received 3 IV treatments in a randomized crossover-design trial with a 2-week washout period between experiments (medetomidine [20 μg/kg], medetomidine [20 μg/kg] and vatinoxan [400 μg/kg], and medetomidine [40 μg/kg] and vatinoxan [800 μg/kg]; M20, M20V400, and M40V800, respectively). Sedation, visceral and somatic nociception, and plasma drug concentrations were assessed. Somatic and visceral nociception measurements and sedation scores were compared among treatments and over time. Sedation, visceral antinociception, and somatic antinociception effects of M20V400 and M40V800 were analyzed for noninferiority to effects of M20, and plasma drug concentration data were assessed for equivalence between treatments.
Plasma dexmedetomidine concentrations after administration of M20 and M40V800 were equivalent. Sedation scores, visceral nociception measurements, and somatic nociception measurements did not differ significantly among treatments within time points. Overall sedative effects of M20V400 and M40V800 and visceral antinociceptive effects of M40V800 were noninferior to those produced by M20. Somatic antinociception effects of M20V400 at 10 minutes and M40V800 at 10 and 55 minutes after injection were noninferior to those produced by M20.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggested coadministration with vatinoxan did not substantially diminish visceral antinociceptive effects of medetomidine when plasma dexmedetomidine concentrations were equivalent to those produced by medetomidine alone. For somatic antinociception, noninferiority of treatments was detected at some time points.