Objective—To determine acute cardiovascular effects
and pharmacokinetics of carvedilol in healthy dogs.
Animals—14 mature healthy Beagles.
Procedure—12 dogs were anesthetized with morphine
and α-chloralose. Catheters were placed in the
aorta, left ventricle, and right atrium to record systemic
and pulmonary pressures and determine vascular
resistance and cardiac output. Electrocardiograms
(leads I, aVF, and V3) were recorded to
determine electrocardiographic changes. Variables
were measured before and after IV injection of incremental
doses of carvedilol (cumulative doses, 10, 30,
70, 150, 310, and 630 μg/kg of body weight;
n = 6) or vehicle alone (6). Pharmacokinetic analysis
was performed, using 2 conscious dogs given 160 mg
of carvedilol/kg as a single IV injection.
Results—Heart rate and velocity of fiber shortening at
zero load (Vmax) increased slightly but significantly from
baseline values at doses of carvedilol ≥ 310 μg/kg and
10 μg/kg, respectively. Carvedilol did not affect systemic
and pulmonary pressures or vascular resistances.
Intravenous administration of approximately 150 μg of
carvedilol/kg resulted in a plasma carvedilol concentration
of approximately 100 ng/ml. Mean elimination halflife
was 54 minutes, half-life of distribution was 3.5
minutes, and volume of distribution was 2,038 ml/kg.
Conclusions and Clinical Relevance—The therapeutic
plasma concentration of carvedilol in humans
is 100 ng/ml. At that plasma concentration in dogs,
the reduction in afterload and positive inotropic effect
that we observed would be beneficial for treating
heart failure and minimizing the cardiotoxic effects of
doxorubicin. (Am J Vet Res 2000;61:57–60)
Objective—To evaluate the use of 24-hour ambulatory
electrocardiography (AECG) for the detection of ventricular
premature complexes (VPC) in healthy dogs.
Animals—50 healthy mature dogs.
Procedure—A 24-hour AECG was performed on each
dog and evaluated for the presence of VPC.
Results—Fifty dogs weighing between 18.2 to 40.9 kg
(40 and 90 lb) representing 13 breeds were evaluated;
there were 4 sexually intact females, 21 spayed
females, 4 sexually intact males, and 21 castrated
males. Ages ranged from 1 to 12 years. Thirty-four dogs
had no VPC; 16 dogs had between 1 and 24 VPC. The
grade of arrhythmia ranged from 1 to 4, with 4 dogs
having an arrhythmia with a grade > 1. Significant differences
were not detected between the group of
dogs with VPC and those without VPC with regard to
sex, age, and minimum, maximum, or mean heart rate.
Conclusions and Clinical Relevance—We conclude
that healthy mature dogs have infrequent VPC, as
detected by use of 24-hour AECG. The presence of
numerous or sequential VPC may be suggestive of
cardiac or systemic disease and may indicate the
need for thorough clinical evaluation. (J Am Vet Med
Objective—To evaluate the use of in-hospital electrocardiography
(ECG) for detection of ventricular premature
complexes (VPC), compared with 24-hour
Animals—188 Boxers > 9 months old; 31 had a history
of syncope, and 157 were healthy (no history of
Procedure—In-hospital ECG was performed on all
Boxers for at least 2 minutes. Within 7 days after the
in-hospital ECG was completed, 24-hour ambulatory
ECG was performed.
Results—The specificity of in-hospital ECG was
100% for the detection of at least 50 VPC in a 24-hour
period in dogs with syncope and 93% in healthy dogs.
In-hospital ECG had poor sensitivity, although sensitivity
increased as the number of VPC per 24 hours
Conclusions and Clinical Relevance—Use of in-hospital
ECG is highly specific for detection of at least 50
VPC during a 24-hour period. However, in-hospital
ECG is insensitive, and a lack of VPC does not suggest
that the dog does not have a substantial number
of VPC during that same period. The use of in-hospital
ECG appears to be inadequate for screening purposes
and therapeutic evaluations in mature Boxers with
ventricular arrhythmic disease. (J Am Vet Med Assoc
Objective—To determine whether QT interval is prolonged
or sudden death is caused by ventricular fibrillation
resulting from torsades de pointes and to identify
hemodynamic effects of ontazolast.
Procedure—Physiologic variables were measured for
2 hours in conscious dogs given ontazolast (0, 1, or 3
mg/kg of body weight, IV) and for 1 hour in anesthetized
dogs given cumulative doses of ontazolast
(0, 1, 3, 6, or 8 mg/kg, IV).
Results—Ontazolast prolonged QT interval and QT
interval corrected for heart rate (QTc) at doses of 6
mg/kg in anesthetized dogs. At 8 mg/kg, both variables
remained prolonged but tended to decrease.
In conscious dogs, ontazolast increased QT interval
and QTc 15 minutes after administration, but both
variables returned to reference ranges by 60 minutes.
In conscious dogs, ontazolast increased maximum
rate of increase of left ventricular pressure
and maximal velocity of fiber shortening, indicators
of inotropy, and increased tau, indicating a
decreased rate of relaxation. One conscious dog
receiving 3 mg/kg developed nonfatal torsades de
pointes, but another conscious dog developed ventricular
fibrillation. Two anesthetized dogs receiving
6 mg/kg developed early afterdepolarizations, and
all dogs developed secondary components in their T
Conclusion and Clinical Relevance—Ontazolast
possesses potent class-III antiarrhythmic properties
and induces prolongation of QTc in a dose-dependent
fashion. Because there was a clear dosedependent
prolongation of QT interval in all
instances, ontazolast may serve as a positive-control
compound for studying other compounds that are
believed to prolong the QT interval. (Am J Vet Res
Objective—To determine the effects of rapid small-volume fluid administration on arterial blood pressure measurements and associated hemodynamic variables in isoflurane-anesthetized euvolemic dogs with or without experimentally induced hypotension.
Design—Prospective, randomized, controlled study.
Animals—13 healthy dogs.
Procedures—Isoflurane-anesthetized dogs were randomly assigned to conditions of nonhypotension or hypotension (mean arterial blood pressure, 45 to 50 mm Hg) and treatment with lactated Ringer's solution (LRS) or hetastarch (3 or 10 mL/kg [1.4 or 4.5 mL/lb] dose in a 5-minute period or 3 mL/kg dose in a 1-minute period [4 or 5 dogs/treatment; ≥ 10-day interval between treatments]). Hemodynamic variables were recorded before and for up to 45 minutes after fluid administration.
Results—IV administration of 10 mL/kg doses of LRS or hetastarch in a 5-minute period increased right atrial and pulmonary arterial pressures and cardiac output (CO) when dogs were nonhypotensive or hypotensive, compared with findings before fluid administration; durations of these effects were greater after hetastarch administration. Intravenous administration of 3 mL of hetastarch/kg in a 5-minute period resulted in an increase in CO when dogs were nonhypotensive. Intravenous administration of 3 mL/kg doses of LRS or hetastarch in a 1-minute period increased right atrial pressure and CO when dogs were nonhypotensive or hypotensive.
Conclusions and Clinical Relevance—Administration of LRS or hetastarch (3 or 10 mL/kg dose in a 5-minute period or 3 mL/kg dose in a 1-minute period) improved CO in isoflurane-anesthetized euvolemic dogs with or without hypotension. Overall, arterial blood pressure measurements were a poor predictor of the hemodynamic response to fluid administration.
Objective—To determine the hematologic, serum biochemical, rheological, hemodynamic, and renal effects of IV administration of lactated Ringer's solution (LRS) to healthy anesthetized dogs.
Design—4-period, 4-treatment cross-over study.
Animals—8 healthy mixed-breed dogs.
Procedures—Each dog was anesthetized, mechanically ventilated, instrumented, and randomly assigned to receive LRS (0, 10, 20, or 30 mL/kg/h [0, 4.5, 9.1, or 13.6 mL/lb/h]), IV, on 4 occasions separated by at least 7 days. Blood hemoglobin concentration and serum total protein, albumin, lactate, and electrolyte concentrations; PCV; colloid osmotic pressure; arterial and venous pH and blood gases (Po2; Pco2); whole blood and plasma viscosity; arterial and venous blood pressures; cardiac output; results of urinalysis; urine production; glomerular filtration rate; and anesthetic recovery times were monitored. Oxygen delivery, vascular resistance, stroke volume, pulse pressure, and blood and plasma volume were calculated.
Results—Increasing rates of LRS administration resulted in dose-dependent decreases in PCV; blood hemoglobin concentration and serum total protein and albumin concentrations; colloid osmotic pressure; and whole blood viscosity. Plasma viscosity; serum electrolyte concentrations; data from arterial and venous blood gas analysis; glomerular filtration rate; urine production; heart rate; pulse, central venous, and arterial blood pressures; pulmonary vascular resistance; and oxygen delivery did not change. Pulmonary artery pressure, stroke volume, and cardiac output increased, and systemic vascular resistance decreased.
Conclusions and Clinical Relevance—Conventional IV infusion rates of LRS to isoflurane-anesthetized dogs decreased colligative blood components; increased plasma volume, pulmonary artery pressure, and cardiac output; and did not change urine production or oxygen delivery to tissues.
Objective—To determine the feasibility for use of a 6-
minute walk test (6-MWT) in dogs with congestive
heart failure (CHF) and document that the distance
walked in 6 minutes decreases when a dog has CHF.
Animals—16 young mature male hound-crossbred
dogs weighing between 25 and 37 kg.
Procedure—An unobstructed path (22.73 m) was
measured in a hallway. Each dog was walked on a
leash for 6 minutes; each dog was allowed to set its
own pace. At the end of 6 minutes (as measured by
use of a stopwatch), the total distance walked was
measured. Heart rate (HR) obtained by auscultation
and mean systemic arterial pressure (MAP) obtained
by oscillometry were recorded before and after the 6-
MWT. Heart failure was induced by use of rapid ventricular
pacing. Mean of the distance walked, HR, and
MAP before and after the 6-MWT were compared
between the control period and after dogs developed
Results—Dogs with CHF had a significant increase in
resting HR, significant decrease in MAP, and a significant
decrease in the distance walked in 6 minutes.
The MAP increased slightly after exercise during the
control period but decreased slightly after exercise
during the CHF period. Fractional shortening
decreased significantly when dogs had CHF.
Conclusions and Clinical Relevance—Analysis of
these results indicated that the distance walked in 6
minutes decreased significantly when a dog had CHF.
The 6-MWT requires little time, space, or equipment
and may replace the treadmill exercise test. ( Am J Vet Res 2004;65:311–313)
Objective—To measure QT interval duration and QT
dispersion in Boxers and to determine whether QT
variables correlate with indices of disease severity in
Boxers with familial ventricular arrhythmias, including
the number of ventricular premature complexes per
day, arrhythmia grade, and fractional shortening.
Animals—25 Boxers were evaluated by ECG and
Procedure—The QT interval duration was measured
from 12-lead ECG and corrected for heart rate (QTc),
using Fridericia's formula. The QT and QTc were calculated
for each lead, from which QT and QTc dispersion
were determined. Echocardiography and 24-hour
ambulatory ECG were performed to evaluate for
familial ventricular arrhythmias. Total number of ventricular
premature complexes, arrhythmia grade, and
fractional shortening were determined and used as
indices of disease severity.
Results—There was no correlation between any QT
variable and total number of ventricular premature
complexes, arrhythmia grade, or fractional shortening.
No difference between QT dispersion and QTc
dispersion was identified, and correction for heart rate
did not affect the results.
Conclusions and Clinical Relevance—QT interval
duration and dispersion did not correlate with indices
of disease severity for familial ventricular arrhythmias.
Heart rate correction of the QT interval did not appear
to be necessary for QT dispersion calculation in this
group of dogs. QT dispersion does not appear to be a
useful noninvasive diagnostic tool in the evaluation of
familial ventricular arrhythmias of Boxers.
Identification of affected individuals at risk for sudden
death remains a challenge in the management of this
disease. (Am J Vet Res 2001;62:1481–1485)
Objective—To describe neuroendocrine responses
that develop in dogs subjected to prolonged periods
of ventricular pacing.
Animals—14 adult male hound-type dogs.
Procedure—Samples were obtained and neuroendocrine
responses measured before (baseline) and
after 3 periods of ventricular pacing. A pacemaker
was used to induce heart rates of 180, 200, and 220
beats/min (BPM). Each heart rate was maintained for
3 weeks before increasing to the next rate. Atrial
natriuretic peptide, antidiuretic hormone, aldosterone,
norepinephrine, epinephrine, and dopamine
concentrations and plasma renin activity were measured.
Severity of left ventricular compromise was
Results—Shortening fraction decreased significantly
with increasing heart rates (mean ± SE, 35.5 ± 1.4,
25.0 ± 1.4, 19.5 ± 1.9, and 12.2 ± 2.3 for baseline, 180
BPM, 200 BPM, and 220 BPM, respectively). Atrial
natriuretic peptide concentrations increased significantly
at 180 BPM (44.1 ± 3.0 pg/mL) and 200 BPM
(54.8 ± 5.5 pg/mL), compared with baseline concentration
(36.8 ± 2.6 pg/mL). Dopamine concentration
increased significantly at 200 BPM (70.4 ± 10.4
pg/mL), compared with baseline concentration (44.2
± 7.3 pg/mL). Norepinephrine concentrations
increased significantly from baseline concentration
(451 ± 46.2 pg/mL) to 678 ± 69.8, 856 ± 99.6, and
1,003 ± 267.6 pg/mL at 180, 200, and 220 BPM,
Conclusions and Clinical Relevance—Dogs subjected
to ventricular pacing for 9 weeks developed neuroendocrine
responses similar to those that develop
in humans with more chronic heart failure and, except
for epinephrine concentrations, similar to those for
dogs subjected to ventricular pacing for < 6 weeks.
(Am J Vet Res 2002;63:1413–1417)
Objective—To evaluate the effect of 4 antiarrhythmic
treatment protocols on number of ventricular premature
complexes (VPC), severity of arrhythmia, heart
rate (HR), and number of syncopal episodes in Boxers
with ventricular tachyarrhythmias.
Design—Randomized controlled clinical trial.
Procedure—Dogs with > 500 VPC/24 h via 24-hour
ambulatory ECG (AECG) were treated with atenolol
(n = 11), procainamide (11), sotalol (16), or mexiletine
and atenolol (11) for 21 to 28 days. Results of pre- and
posttreatment AECG were compared with regard to
number of VPC/24 h; maximum, mean, and minimum
HR; severity of arrhythmia; and occurrence of syncope.
Results—Significant differences between pre- and
posttreatment number of VPC, severity of arrhythmia,
HR variables, or occurrence of syncope were not
observed in dogs treated with atenolol or procainamide.
Significant reductions in number of VPC,
severity of arrythmia, and maximum and mean HR
were observed in dogs treated with mexiletineatenolol
or sotalol; occurrence of syncope was not significantly
different between these 2 treatment groups.
Conclusions and Clinical Relevance—Treatment
with sotalol or mexiletine-atenolol was well tolerated
and efficacious. Treatment with procainamide or
atenolol was not effective. (J Am Vet Med Assoc 2002;221:522–527)