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- Author or Editor: Robert L. Hamlin x
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Abstract
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)
Abstract
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.
Animals—28 Beagles.
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 waves.
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 2000;61:1364–1368)
Abstract
Objective—To evaluate the use of in-hospital electrocardiography (ECG) for detection of ventricular premature complexes (VPC), compared with 24-hour ambulatory ECG.
Design—Original study.
Animals—188 Boxers > 9 months old; 31 had a history of syncope, and 157 were healthy (no history of syncope).
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 increased.
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 2001;218:222–224)
Abstract
Objective—To evaluate the use of 24-hour ambulatory electrocardiography (AECG) for the detection of ventricular premature complexes (VPC) in healthy dogs.
Design—Case series.
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 Assoc 2001;218:1291–1292)
Abstract
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.
Abstract
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 estimated.
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, respectively.
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)
Abstract
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 induced CHF.
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)
Abstract
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 echocardiography.
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)
Abstract
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 (Po 2; Pco 2); 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.
Abstract
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.
Animals—49 Boxers.
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)
