Objective—To determine the effects of xylazine on
canine coronary artery smooth muscle tone.
Sample Population—Hearts of 26 healthy dogs.
Procedure—Dogs were anesthetized with pentobarbital,
and vascular rings of various diameters were
prepared from the epicardial coronary arteries.
Vascular rings were placed in tissue baths to which
xylazine was added (cumulative concentrations ranging
from 10–10 to 10–4M), and changes in vascular ring
tension were continuously recorded. Effects of the
nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME;
5mM), the α1-adrenoceptor antagonist prazosin
(10mM), and the α2-adrenoceptor antagonist atipamezole
(10mM) on xylazine-induced changes in
vascular ring tension were determined. Results were
expressed as percentage of maximal contraction for
each vascular ring preparation.
Results—Xylazine induced vasoconstriction of small
(< 500-µm-diameter) and medium (500- to 1,000-µmdiameter)
vascular rings but not of large (> 1,000-µmdiameter)
rings. For large vascular rings, L-NAME, atipamezole,
and prazosin did not significantly affect the
contractile response to xylazine. For small vascular
rings, the contractile response following addition of
xylazine to rings treated with L-NAME was not significantly
different from the contractile response following
addition of xylazine to control rings, except at a
xylazine concentration of 10–6M. Xylazine-induced
vasoconstriction of small vascular rings was blocked
by atipamezole, but the addition of prazosin had no
effect on xylazine-induced vasoconstriction.
Conclusions and Clinical Relevance—Results suggest
that xylazine increases smooth muscle tone of
small canine coronary arteriesand that this effect is predominantly
mediated by stimulation of α2adrenoceptors.(
Am J Vet Res 2004;65:431–435)
Objective—To evaluate the effects of the α2-adrenoceptor
agonist medetomidine on respiratory rate
(RR), tidal volume (VT), minute volume (VM), and central
respiratory neuromuscular drive as determined by
inspiratory occlusion pressure (IOP) during increasing
fractional inspired concentrations of carbon dioxide
(FiCO2) in conscious dogs.
Animals—6 healthy dogs (3 males and 3 females).
Procedure—Dogs were administered 0, 5, or 10 µg of
medetomidine/kg IV. We measured RR, VT, VM, and
IOP for the first 0.1 second of airway occlusion
(IOP0.1) during FiCO2 values of 0%, 2.5%, 5.0%, and
7.5% at 15 minutes before and 5, 30, and 60 minutes
after administration of medetomidine.
Results—Increases in FiCO2 significantly increased
RR, VT, and VM. The IV administration of 5 and 10 µg
of medetomidine/kg significantly decreased RR and
VM at 5, 30, and 60 minutes for FiCO2 values of 2.5%
and 5.0% and at 30 and 60 minutes for an FiCO2 value
of 7.5%. The IOP0.1 was decreased after 30 minutes
only for an FiCO2 value of 7.5% in dogs administered
5 and 10 µg of medetomidine/kg. The IOP0.1 was
decreased at 60 minutes after administration of 10 µg
of medetomidine/kg for an FiCO2 value of 7.5%.
Conclusions and Clinical Relevance—The IV administration
of medetomidine decreases RR, VM, and
central respiratory drive in conscious dogs.
Medetomidine should be used cautiously and with
careful monitoring in dogs with CNS depression or
respiratory compromise. (Am J Vet Res 2004;65:
To determine the hemodynamic effects
of IM administration of romifidine hydrochloride in
Animals—15 adult domestic shorthair cats.
Procedure—Cats were randomly assigned to receive
romifidine (0, 400, or 2,000 µg/kg, IM). Cats were
anesthetized with propofol and mechanically ventilated
with oxygen. The right jugular vein, left carotid
artery, and right femoral artery and vein were surgically
isolated and catheterized. Heart rate; duration of
the PR, QRS, and QT intervals; mean pulmonary
artery pressure; mean right atrial pressure; systolic,
diastolic, and mean arterial pressures; left ventricular
systolic pressure; left ventricular end-diastolic pressure;
and cardiac output were monitored. Systemic
vascular resistance, rate of change of left ventricular
pressure, and rate pressure product were calculated.
Arterial and venous blood samples were collected
anaerobically for determination of pH and blood gas
tensions (PO2 and PCO2).
Results—Administration of romifidine at 400 and
2,000 µg/kg, IM, decreased heart rate, cardiac output,
rate of change of left ventricular pressure, rate pressure
product, and pH. Arterial and pulmonary artery
pressures, left ventricular pressure, left ventricular
end-diastolic pressure, and right atrial pressure
increased and then gradually returned to baseline values.
Arterial blood gas values did not change, whereas
venous PCO2 increased and venous PO2 decreased.
Significant differences between low and high
dosages were rare, suggesting that the dosages
investigated produced maximal hemodynamic
Conclusion and Clinical Relevance—Romifidine
produces cardiovascular effects that are similar to
those of other α2-agonists. High dosages of romifidine
should be used with caution in cats with cardiovascular
compromise. (Am J Vet Res 2002;63:1241–1246)
Objective—To evaluate the effect of medetomidine on minimum alveolar concentration (MAC), respiratory rate, tidal volume, minute volume (VM), and maximum inspiratory occlusion pressure (IOCPmax) in halothane- and isoflurane-anesthetized dogs.
Animals—6 healthy adult dogs (3 males and 3 females).
Procedure—The MAC of both inhalants was determined before and 5, 30, and 60 minutes after administration of medetomidine (5 μg/kg, IV). Dogs were subsequently anesthetized by administration of halothane or isoflurane and administered saline (0.9% NaCl) solution IV or medetomidine (5 μg/kg, IV). Respiratory variables and IOCPmax were measured at specific MAC values 15 minutes before and 5, 30, and 60 minutes after IV administration of medetomidine while dogs breathed 0% and 10% fractional inspired carbon dioxide (FICO2). Slopes of the lines for VM/FICO2 and IOCPmax/FICO2 were then calculated.
Results—Administration of medetomidine decreased MAC of both inhalants. Slope of VM/FICO2 increased in dogs anesthetized with halothane after administration of medetomidine, compared with corresponding values in dogs anesthetized with isoflurane. Administration of medetomidine with a simultaneous decrease in inhalant concentration significantly increased the slope for VM/FICO2, compared with values after administration of saline solution in dogs anesthetized with halothane but not isoflurane. Values for IOCPmax did not differ significantly between groups.
Conclusions and Clinical Relevance—Equipotent doses of halothane and isoflurane have differing effects on respiration that are most likely attributable to differences in drug effects on central respiratory centers. Relatively low doses of medetomidine decrease the MAC of halothane and isoflurane in dogs.
Objective—To compare the effects of lactated
Ringer's solution (LRS) with those of a physiologically
balanced 6% hetastarch plasma expander administered
to isoflurane-anesthetized dogs with hypotension
induced by blood withdrawal.
Animals—12 healthy Beagles.
Procedure—Blood was withdrawn from isofluraneanesthetized
dogs (volume withdrawn measured) to a
systolic arterial blood pressure (SAP) of 80 mm Hg.
Six dogs each received either LRS or hetastarch solution
(90 mL/kg/h, IV). Hemodynamic variables, pH,
blood gas concentrations, PCV, serum electrolyte and
total protein concentrations, and colloid osmotic pressure
(COP) were determined at baseline, while SAP
was 80 mm Hg, and after fluid treatment. The volume
of fluid administered and rate of return of SAP to within
10% of baseline values were recorded.
Results—Mean ± SD volume of blood withdrawn to
decrease SAP to 80 mm Hg was 173 ± 38 mL.
Hemodynamic variables decreased after blood withdrawal
but returned to baseline values more rapidly
after infusion of a smaller volume of hetastarch solution,
compared with the response to LRS infusion.
Whereas PCV and serum total protein concentration
decreased after administration of either solution, COP
decreased only after administration of LRS. The total
volume of hetastarch solution and LRS required to
restore and maintain SAP to within 10% of baseline
values was 1.1 ± 0.9 and 4.4 ± 1.7 times greater than
the volume of blood removed, respectively.
Conclusions and Clinical Relevance—Compared
with LRS infusion, smaller volumes of hetastarch
solution normalized and maintained SAP without lowering
COP in isoflurane-anesthetized dogs after blood
withdrawal. (Am J Vet Res 2004;65:1189–1194)
Objective—To determine the analgesic, hemodynamic,
and respiratory effects induced by caudal
epidural administration of meperidine hydrochloride in
Animals—7 healthy mares.
Procedure—Each mare received meperidine (5%;
0.8 mg/kg of body weight) or saline (0.9% NaCl) solution
via caudal epidural injection on 2 occasions. At
least 2 weeks elapsed between treatments. Degree
of analgesia in response to noxious electrical, thermal,
and skin and muscle prick stimuli was determined
before and for 5 hours after treatment. In addition,
cardiovascular and respiratory variables were
measured and degree of sedation (head position) and
ataxia (pelvic limb position) evaluated.
Results—Caudal epidural administration of meperidine
induced bilateral analgesia extending from the
coccygeal to S1 dermatomes in standing mares;
degree of sedation and ataxia was minimal. Mean (±
SD) onset of analgesia was 12 ± 4 minutes after
meperidine administration, and duration of analgesia
ranged from 240 minutes to the entire 300-minute
testing period. Heart and respiratory rates, rectal temperature,
arterial blood pressures, Hct, PaO2, PaCO2,
pHa, total solids and bicarbonate concentrations, and
base excess were not significantly different from
baseline values after caudal epidural administration of
either meperidine or saline solution.
Conclusions and Clinical Relevance—Caudal
epidural administration of meperidine induced prolonged
perineal analgesia in healthy mares. Degree of
sedation and ataxia was minimal, and adverse cardiorespiratory
effects were not detected. Meperidine
may be a useful agent for induction of caudal epidural
analgesia in mares undergoing prolonged diagnostic,
obstetric, or surgical procedures in the anal and
perineal regions. (Am J Vet Res 2001;62:1001–1007)
Objective—To compare the minimum alveolar concentration
(MAC) of isoflurane required to prevent
corticocerebral activation, autonomic responses, and
purposeful movements after somatic or visceral stimulation
in cats anesthetized with isoflurane.
Animals—17 healthy spayed female cats.
Procedure—Bispectral index (BIS), autonomic parameters,
and purposeful movements were monitored
before and after somatic or visceral stimuli in cats
anesthetized with isoflurane. End-tidal (ET) isoflurane
concentration was varied to determine MAC values
for cortical arousal (MACBIS), autonomic responsiveness
(MACBAR), and purposeful movement (MAC).
Bispectral index values ≥ 60 were considered to represent
Results—Minimum alveolar concentration for purposeful
movement was significantly less than MACBIS
and MACBAR for both somatic and visceral stimulation.
Individual MAC values for somatic stimulation were
not significantly different from respective MAC values
for visceral stimulation. The percentage of cats that
had a BIS response ≥ 60 was inversely related to the
end-tidal isoflurane concentration.
Conclusions and Clinical Relevance—Corticocerebral
arousal and subcortical autonomic reflexes occured at
isoflurane anesthetic concentrations at which reflexive
or purposeful movements were absent. These results
suggested that isoflurane had a preferential effect on
voluntary motor output at low end-tidal isoflurane concentrations,
and that sensory pathways, subcortical
sympathetic output, and cortical responsiveness are
less susceptible to the anesthetic effects of isoflurane.
Bispectral index values obtained after somatic or visceral
stimulation were sensitive for the detection of early
changes in cortical excitability. (Am J Vet Res 2003;
Objective—To determine whether the prestimulation
bispectral index (BIS) value or relative change in BIS
after noxious stimulation can be used to assess the
depth of isoflurane anesthesia in cats.
Animals—17 healthy female cats.
Procedure—Electroencephalogram (EEG) patterns
and BIS values were examined in cats that received
increasing end-tidal (ET) isoflurane concentrations.
Subsequently, BIS values were determined before
and after either a noxious somatic or visceral stimulus
in cats that received ET isoflurane concentrations
ranging from 1.8% to 2.4%. Electrical stimuli of the
tail base and bladder distension to 50 cm of water
were the somatic and visceral stimuli, respectively.
Results—The resting BIS at ET isoflurane concentrations
from 1.4% to 1.9% steadily decreased concurrently
with increasing degrees of EEG suppression.
Prestimulation BIS values, however, were not related
to 1.8% to 2.4% ET isoflurane concentrations and not
useful for prediction of BIS values or hemodynamic
and movement responses after a noxious stimulus.
The poststimulation BIS value and the difference
between mean BIS values before and after stimulation
were inversely correlated with increasing ET
isoflurane concentrations. Poststimulation BIS values
> 60 were observed at ET isoflurane concentrations
greater than those associated with a movement
response after a stimulus.
Conclusions and Clinical Relevance—The prestimulation
BIS value has limited use in assessing anesthetic
depth in cats during isoflurane anesthesia. The
change in BIS values after a noxious somatic or visceral
stimulus was a reliable measure of anesthetic
depth and may be a useful measure of early arousal
from the hypnotic state. (Am J Vet Res 2003;64:1534–1541)
Objective—To compare effects of electroacupuncture
and butorphanol on hemodynamic and respiratory
variables and rectal analgesia in mares after controlled
Animals—8 healthy mares.
Procedure—Each horse received saline (0.9% NaCl)
solution (0.01 mL/kg, IV; control treatment), butorphanol
tartrate (0.1 mg/kg, IV), or 2 hours of electroacupuncture
(EA) at acupoints Bladder 21, 25, and
27 on both sides of the vertebral column, Bai hui, and
Stomach 36 (right side only). Order of treatments in
each mare was randomized. At least 7 days elapsed
between treatments. A balloon was inserted in the
rectum of each mare, and controlled distention of the
balloon (pressures of ≤ 220 mm Hg) was used to measure
nociceptive rectal pain threshold. Rectal temperature
and cardiovascular and respiratory variables
were measured before (baseline) and 5, 15, 30, 60, 90,
and 120 minutes after onset of each treatment.
Results—Butorphanol produced greater increases in
rectal pain threshold, compared with EA (mean ± SD,
214 ± 24 vs 174 ± 35 mm Hg of balloon pressure).
Electroacupuncture produced minimal cardiovascular
and respiratory changes. Although clinically not important,
butorphanol produced moderate significant
increases in heart and respiratory rates, arterial blood
pressure, and rectal temperature and decreases in
arterial oxygen tension. Arterial pH, carbon dioxide
tension, bicarbonate concentrations, base excess,
Hct, and concentration of total solids were not significantly
different from baseline values after EA, butorphanol,
and control treatments.
Conclusions and Clinical Relevance—Electroacupuncture
and butorphanol (0.1 mg/kg, IV) may provide
useful rectal analgesia in horses. (Am J Vet Res 2003;64:137–144)
Objective—To compare the cardiorespiratory, gastrointestinal, analgesic, and behavioral effects between IV and IM administration of morphine in conscious horses with no signs of pain.
Animals—6 healthy adult horses.
Procedures—Horses received saline (0.9% NaCl) solution (IM or IV) or morphine sulfate (0.05 and 0.1 mg/kg, IM or IV) in a randomized, masked crossover study design. The following variables were measured before and for 360 minutes after drug administration: heart and respiratory rates; systolic, diastolic, and mean arterial blood pressures; rectal temperature; arterial pH and blood gas variables; intestinal motility; and response to thermal and electrical noxious stimuli. Adverse effects and horse behavior were also recorded. Plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were measured via liquid chromatography–mass spectrometry.
Results—No significant differences in any variable were evident after saline solution administration. Intravenous and IM administration of morphine resulted in minimal and short-term cardiorespiratory, intestinal motility, and behavioral changes. A decrease in gastrointestinal motility was detected 1 to 2 hours after IM administration of morphine at doses of 0.05 and 0.1 mg/kg and after IV administration of morphine at a dose of 0.1 mg/kg. Morphine administration yielded no change in any horse's response to noxious stimuli. Both morphine-3-glucuronide and morphine-6-glucuronide were detected in plasma after IV and IM administration of morphine.
Conclusions and Clinical Relevance—Clinically relevant doses of morphine sulfate yielded minimal and short-term behavioral and intestinal motility effects in healthy horses with no signs of pain. Neither dose of morphine affected their response to a noxious stimulus.