Objective—To determine the effects of nitrous oxide
(N2O) on the speed and quality of mask induction with
sevoflurane or isoflurane in dogs.
Animals—7 healthy Beagles.
Procedure—Anesthesia was induced with sevoflurane
or isoflurane delivered in 100% oxygen or in a 2:1
mixture of N2O and oxygen via a face mask. Each dog
received all treatments with at least 1 week between
treatments. Initial vaporizer settings were 0.8% for
sevoflurane and 0.5% for isoflurane (0.4 times the
minimum alveolar concentration [MAC]). Vaporizer settings
were increased by 0.4 MAC at 15-second intervals
until settings were 4.8% for sevoflurane and
3.0% for isoflurane (2.4 MAC). Times to onset and cessation
of involuntary movements, loss of the palpebral
reflex, negative response to tail-clamp stimulation, and
endotracheal intubation were recorded, and cardiopulmonary
variables were measured.
Results—Administration of sevoflurane resulted in a
more rapid induction, compared with isoflurane.
However, N2O had no effect on induction time for
either agent. Heart rate, mean arterial blood pressure,
cardiac output, and respiratory rate significantly
increased and tidal volume significantly decreased
from baseline values immediately after onset of induction
in all groups. Again, concomitant administration of
N2O had no effect on cardiopulmonary variables.
Conclusions and Clinical Relevance—Administration
of N2O did not improve the rate or quality of
mask induction with sevoflurane or isoflurane. The
benefits provided by N2O attributable to concentrating
and second gas effects appear minimal in healthy
dogs when low solubility inhalation agents such as
isoflurane and sevoflurane are used for mask induction.
(Am J Vet Res 2001;62:1727–1733).
Objective—To characterize the effects of medetomidine-
midazolam, midazolam-butorphanol, or acepromazine-
butorphanol as premedicants for mask induction
of anesthesia with sevoflurane in dogs.
Animals—10 healthy Beagles.
Procedure—The following premedicants were administered
(20 µg/kg and 0.3 mg/kg, respectively), midazolambutorphanol
(0.1 and 0.2 mg/kg, respectively), and
acepromazine-butorphanol (0.05 and 0.2 mg/kg,
respectively). Saline (0.9% NaCl) solution (0.1 ml/kg)
was administered intramuscularly as a control.
Anesthesia was induced in each dog with sevoflurane
in a 100% O2 at a flow rate of 4 L/min developed by a
facemask. Vaporizer settings were increased by 0.8%
at 15-second intervals until the value corresponding to
4.8% sevoflurane was achieved. Time to onset and
cessation of involuntary movements, loss of the
palpebral reflex, negative response to tail-clamp stimulation,
and endotracheal intubation were recorded,
and the cardiopulmonary variables were measured.
Results—Mask induction with sevoflurane in dogs
that received each premedicant resulted in a shorter
induction time and milder changes in heart rate, mean
arterial blood pressure, cardiac output, and respiratory
rate, compared with mask induction without premedicants.
Treatment with medetomidine-midazolam
resulted in a shorter and smoother induction, compared
with acepromazine-butorphanol or midazolambutorphanol
treatment, whereas the cardiovascular
changes were greater. Cardiopulmonary variables of
dogs during induction following treatment with acepromazine-
butorphanol or midazolam-butorphanol
were maintained close to the anesthetic maintenance
values for sevoflurane, with the exception of mild
hypotension that was observed in dogs following
Conclusion and Clinical Relevance—In dogs use of
premedicants provides a smoother and better quality
mask induction with sevoflurane. (Am J Vet Res
Objective—To characterize and determine the sensory
innervation of respiratory reflexes elicited by nasal
administration of halothane to dogs.
Animals—10 healthy Beagles.
Procedure—Dogs underwent permanent tracheostomy
and, 2 to 3 weeks later, were anesthetized with
thiopental and α-chloralose administered IV. The nasal
passages were functionally isolated so that halothane
could be administered to the nasal passages while
dogs were breathing 100% O2 via the tracheostomy.
Respiratory reflexes in response to administration of
halothane at concentrations of 1.25, 1.75, and 2.5
times the minimum alveolar concentration (MAC), and
5% (administered in 100% O2 at a flow rate of 5 L/min)
were recorded. Reflexes in response to administration
of 5% halothane were also recorded following transection
of the infraorbital nerve, transection of the caudal
nasal nerve, and nasal administration of lidocaine.
Results—Nasal administration of halothane induced
an inhibition of breathing characterized by a dosedependent
increase in expiratory time and a resultant
decrease in expired volume per unit time. Effects
were noticeable immediately after the onset of
halothane administration and lasted until its cessation.
Reflex responses to halothane administration
were attenuated by transection of the caudal nasal
nerve and by nasal administration of lidocaine, but
transection of the infraorbital nerve had no effect.
Conclusions and Clinical Relevance—Nasal administration
of halothane at concentrations generally
used for mask induction of anesthesia induces reflex
inhibition of breathing. Afferent fibers in the caudal
nasal nerve appear to play an important role in the
reflex inhibition of breathing induced by halothane
administration. (Am J Vet Res 2000;61:260–267)
Objective—To evaluate dose-sparing effects of
medetomidine-midazolam (MM), acepromazinebutorphanol
(AB), and midazolam-butorphanol
(MB) on the induction dose of thiopental and
propofol and to examine cardiopulmonary changes
Animals—23 healthy Beagles.
Procedure—Dogs were administered MM, AB, MB,
or physiologic saline (0.9% NaCl) solution (PS) IM,
and anesthesia was induced with thiopental or
propofol. Cardiopulmonary measurements were
obtained before and after administration of medication
and 0, 5, 10, and 15 minutes after endotracheal
Results—Induction doses were reduced significantly
by preanesthetic administration of MM, AB, and
MB (thiopental, 20, 45, and 46% after administration
of PS; propofol, 42, 58, and 74% after administration
of PS, respectively). Recovery time in dogs administered
MM-thiopental or MM-propofol and AB-propofol
were significantly prolonged, compared with
recovery time in dogs administered PS-thiopental or
PS-propofol. Relatively large cardiovascular changes
were induced by administration of MM, which were
sustained even after the induction of anesthesia.
Administration of AB and MB induced cardiovascular
changes during and immediately after endotracheal
intubation that were significantly decreased by
induction with thiopental or propofol. However, mild
hypotension developed with AB-propofol. Apnea
was observed in dogs administered MM during
induction of anesthesia, but most respiratory variables
did not change significantly.
Conclusions and Clinical Relevance—Preanesthetic
medication with MM greatly reduced the anesthesia
induction dose of thiopental and propofol but caused
noticeable cardiopulmonary changes. Preanesthetic
medication with AB and MB moderately reduced the
induction dose of thiopental and propofol and ameliorated
cardiovascular changes induced by these anesthetics,
although AB caused mild hypotension.
(Am J Vet Res 2002;63:1671–1679)
Objective—To determine differentiation and
growth inhibition effects of retinoids on canine
Sample Population—3 osteosarcoma cell lines established
from osteosarcomas in dogs.
Procedure—Osteosarcoma cells were incubated
with various concentrations of all-trans-retinoic acid
and 9-cis-retinoic acid or control medium, counted
daily for 10 days, and evaluated for morphologic
changes. Synthesis of DNA was measured by use of
a cell proliferation ELISA. To analyze effect of
retinoids on colony formation on plastic dishes, cells
were cultured for 14 days, fixed, and stained; number
of colonies was counted.
Results—In a dose-dependent manner, both
retinoids induced morphologic differentiation and
growth inhibition in the 3 osteosarcoma cell lines and
inhibited each cell's ability to form anchorage-dependent
Conclusion and Clinical Relevance—Retinoids
induced differentiation of osteosarcoma cells of dogs,
resulting in altered expression of their malignant phenotype.
Induction of differentiation by retinoids may
have potential as an adjunctive treatment for
osteosarcoma in dogs. (Am J Vet Res 2000;61:69–73)
Procedure—1 × 107 POS osteosarcoma cells were
transplanted subcutaneously into the intrascapular
region of mice. All-trans RA (3 or 30 µg/kg of body
weight in 0.1 ml of sesame oil), 9-cis RA (3 or 30 mg/kg
in 0.1 ml of sesame oil), or sesame oil (0.1 ml; control
treatment) were administered intragastrically 5 d/wk
for 4 weeks beginning 3 days after transplantation (n =
4 mice/group) or after formation of a palpable tumor (5
mice/group). Tumor weight was estimated weekly by
measuring tumor length and width, and retinoid toxic
effects were evaluated daily. Two weeks after the final
treatment, mice were euthanatized, and number of
mice with pulmonary metastases was determined.
Results—Adverse treatment effects were not detected.
Tumor weight was less in mice treated with either
dose of 9-cis RA than in control mice, although this
difference was not significant. Treatment with 30 mg
of 9-cis RA/kg initiated after tumor formation significantly
reduced the incidence of pulmonary metastasis,
compared with the control group.
Conclusions and Clinical Relevance—9-cis RA
decreased the incidence of pulmonary metastasis in
nude mice transplanted with canine osteosarcoma
cells and may be a potential adjunct therapy for treatment
of osteosarcoma in dogs. (Am J Vet Res 2000;
Objective—To characterize respiratory reflexes elicited
by nasal administration of sevoflurane (Sevo),
isoflurane (Iso), or halothane (Hal) in anesthetized
Animals—8 healthy Beagles.
Procedure—A permanent tracheostomy was created
in each dog. Two to 3 weeks later, dogs were anesthetized
by IV administration of thiopental and α-chloralose.
Nasal passages were isolated such that
inhalant anesthetics could be administered to the
nasal passages while the dogs were breathing 100%
O2 via the tracheostomy. Respiratory reflexes in
response to administration of each anesthetic at 1.2
and 2.4 times the minimum alveolar concentration
(MAC) and the full vaporizer setting (5%) were recorded.
Reflexes in response to administration of 5% of
each anesthetic also were recorded following administration
of lidocaine to the nasal passages.
Results—Nasal administration of Sevo, Iso, and Hal
induced an immediate ventilatory response characterized
by a dose-dependent increase in expiratory time
and a resulting decrease in expired volume per unit of
time. All anesthetics had a significant effect, but for
Sevo, the changes were smaller in magnitude.
Responses to administration of each anesthetic were
attenuated by administration of lidocaine to the nasal
Conclusions and Clinical Relevance—Nasal administration
of Sevo at concentrations generally used for
mask induction of anesthesia induced milder reflex
inhibition of breathing, presumably via afferent neurons
in the nasal passages, than that of Iso or Hal.
Respiratory reflexes attributable to stimulation of the
nasal passages may contribute to speed of onset and
could promote a smoother induction with Sevo, compared
with Iso or Hal. (Am J Vet Res 2001;62:311–319)
Objective—To characterize the clinical features of visceral
mast cell tumors (MCT) without associated cutaneous
involvement in dogs.
Animals—10 dogs with histologically confirmed MCT
without associated cutaneous lesions.
Procedure—Information on signalment, clinical signs,
laboratory examinations, and time from first admission
to death was obtained from the medical record
of each dog.
Results—Purebred male dogs of miniature breeds
appeared to have a higher prevalence of visceral MCT.
Clinical signs included anorexia, lethargy, vomiting,
and diarrhea. Anemia (n = 7), hypoproteinemia (5), and
mastocythemia (5) were detected. Treatments, including
glucocorticoids, were not successful. Primary sites
of tumors were the gastrointestinal tract (n = 6) and
the spleen or liver (1); the primary site was not confirmed
in the remaining 3 dogs. In 7 dogs, tumors
were categorized as grade II or III, on the basis of histologic
findings. The prognoses were poor, and all
dogs died within 2 months after first admission.
Conclusions and Clinical Relevance—Visceral MCT
is uncommon in dogs, and the prognosis is extremely
poor. Biological behavior and drug susceptibility of
visceral MCT may be different from cutaneous MCT.
The lack of specific clinical signs may result in delay of
a definitive diagnosis. The rapid progression of clinical
signs and difficulty in diagnosis contributes to a short
survival time. ( J Am Vet Med Assoc 2000;216:
Objective—To measure telomere length and telomerase
activity in naturally occurring canine mammary
Sample Population—27 mammary gland tumor
specimens obtained during resection or necropsy and
12 mammary gland tissue specimens obtained from
healthy (control) dogs.
Procedure—Telomere length in tissue specimens
was measured by use of restriction endonuclease
digestion and Southern blot analysis. Telomerase
activity was measured by use of a telomeric repeat
amplification protocol assay.
Results—Telomere length in mammary gland tumors
ranged from 11.0 to 21.6 kilobase pairs (kbp; mean ±
SEM, 14.5 ± 0.5 kbp) but did not differ among tumor
types. Telomeres in mammary gland tumors were
slightly shorter than in normal tissue specimens, but
telomere length could not be directly compared
between groups, because mean age of dogs was significantly
different between groups. Age was negatively
correlated with telomere length in control dogs
but was not significantly correlated with length in
affected dogs. Telomerase activity was detected in 26
of 27 mammary gland tumors and in 4 of 12 normal
tissue specimens. However, telomerase activity and
telomere length were not correlated in tumor specimens.
Conclusion and Clinical Relevance—Telomere
length is maintained in canine mammary gland
tumors regardless of the age of the affected dog.
Measurement of telomere length may be a useful
tool for monitoring the in vivo effects of telomerase
inhibitors in dogs with tumors. (Am J Vet Res 2001;
Objective—To evaluate aberrations of the p53 tumor
suppressor gene in naturally developing tumors in
Sample Population—Tumor specimens from 15
dogs with various tumors, including malignant lymphoma
(7 dogs), monocytic leukemia (1), mammary
gland adenoma (1), mammary gland benign mixed
tumor (1), rhabdomyosarcoma (1), colon cancer (1),
and osteosarcoma (3).
Procedure—Aberrations of the p53 gene in these
tumor tissues were examined by reverse transcriptase-
polymerase chain reaction and single-strand conformation
polymorphism analysis, using 3 fragments
that covered the entire open reading frame of the
canine p53 gene, followed by nucleotide sequencing
of the abnormal bands.
Results—Point mutations, deletions, and insertions
resulting in a number of amino acid substitutions of
wild-type p53 were detected in 7 of the 15 tumor
specimens from dogs with malignant lymphoma,
monocytic leukemia, rhabdomyosarcoma, colon cancer,
and osteosarcoma. Of these 7 dogs, 2 had aberrations
of the p53 gene on both alleles, whereas 5
had aberrations of the p53 gene on 1 allele and concurrently
lacked the wild-type p53 transcript. Many of
the aberrations of the p53 gene detected in these
tumors were located in the transactivation, DNA binding,
and oligomerization domains.
Conclusions and Clinical Relevance—Various naturally
developing tumors in dogs often have inactivation
of the p53 tumor suppressor gene, which may be
1 of the multiple step-wise genetic changes during
tumorigenesis. This study indicates that p53 gene can
be a target for gene therapy for tumors in dogs. (Am
J Vet Res 2001;62:433–439)