Toxicity in Doberman Pinchers with Ventricular Arrhythmias Treated with Amiodarone (1996–2005)

Background: Asymptomatic Doberman Pinschers with dilated cardiomyopathy (DCM) often die suddenly owing to ventricular tachycardia that degenerates into ventricular fibrillation. A safe and effective antiarrhythmic drug treatment is needed. This will require a large, well-controlled, prospective study.
Hypothesis: Amiodarone toxicity is common in Dobermans with occult DCM and ventricular tachyarrhythmias refractory to antiarrhythmia therapy. Infrequent monitoring of hepatic function is inadequate. Frequent monitoring may be useful to determine dogs in which the dosage should be decreased or the drug withdrawn.
Methods: Medical records from the University of Georgia and Cornell University were searched for Doberman Pinschers diagnosed with preclinical DCM that received amiodarone for severe ventricular arrhythmias refractory to other antiarrhythmic agents. Echocardiographic data, Holter recording data, hepatic enzyme serum activity, and serum amiodarone concentrations were recorded. The presence of clinical signs of toxicity was recorded. Serum amiodarone concentrations were obtained in some dogs.
Results: Reversible toxicity was identified in 10 of 22 (45%) dogs.
Conclusion and Clinical Importance: Adverse effects from amiodarone were common and were, in part, dosage related. Patients should be monitored for signs of toxicity and liver enzyme activity should be measured at least monthly.     

Pharmacodynamic effects of ivabradine, a negative chronotropic agent, in healthy cats

Objective

To determine the pharmacodynamic effects of oral ivabradine in cats.

Animals

Eight healthy, adult domestic short hair cats.

Methods

Each cat underwent four study periods of 24 h, receiving either one dose of placebo or ivabradine (0.1 mg/kg, 0.3 mg/kg, and 0.5 mg/kg) in a single-blind randomized crossover study. Clinical tolerance was assessed hourly for the first 8 h, at 12 h, and at the end of the 24-h study period. Heart rate and blood pressure were monitored continuously for 18–24 h via radiotelemetry after each treatment. Response to stress (acoustic startle) was studied before (t = 0) and after treatment (t = 4 h). Statistical comparisons were made using a linear mixed models and 1-way and 2-way repeated measures ANOVA.

Results

Heart rate (min⁻¹) decreased significantly (P < 0.05) in a dose-dependent manner with peak negative chronotropic effects observed 3 h after ivabradine (mean ± SD; placebo, 144 ± 20; ivabradine 0.1 mg/kg, 133 ± 22; ivabradine 0.3 mg/kg, 112 ± 20; and ivabradine 0.5 mg/kg, 104 ± 11). Heart rate (min⁻¹) was still reduced (P < 0.05) 12 h after ivabradine (0.3 mg/kg; 128 ± 18 and 0.5 mg/kg; 124 ± 16) compared to placebo (141 ± 21). The tachycardic response to acoustic startle was significantly (P < 0.01) blunted at all 3 doses of ivabradine. Myocardial oxygen consumption estimated by the rate-pressure product was significantly reduced (P < 0.05) for all doses of ivabradine. No effect of ivabradine on systolic, diastolic, and mean blood pressure was identified and no clinically discernable side effects were observed.

Conclusion

These findings indicate that a single oral dose of ivabradine predictably lowers heart rate, blunts the chronotropic response to stress, and is clinically well tolerated in healthy cats. This makes ivabradine potentially interesting in the treatment of feline heart disease where ischemia is of pathophysiologic importance.     

Adverse Effects of Zilpaterol Administration in Horses: Three Cases

Three healthy horses were fed the beta-adrenergic agonist feed additive zilpaterol at a dosage of 0.17 mg/kg body weight to study zilpaterol elimination kinetics. Soon after ingestion of zilpaterol, the horses developed skeletal muscle tremors and tachycardia. A 75 to 87.5% reduced dose of zilpaterol was fed to the horses 24 hours after the initial dose; administration was discontinued thereafter. The horses exhibited restlessness, muscle tremors, and profuse sweating 20 to 25 minutes after ingestion of zilpaterol. Tachycardia developed within 40 minutes and took up to 2 weeks to resolve. Muscle tremors lasted up to 1 week. The most pronounced derangements in serum biochemistry were increased activities of lactic dehydrogenase, creatine kinase, and aspartate transferase, indicating muscle damage. The most severely affected horse also had transient azotemia, hematuria, and proteinuria, suggesting renal damage. All three horses recovered without treatment and were clinically normal 2 to 3 weeks after the initial dose of zilpaterol. Because of their anabolic properties, beta-adrenergic feed additives are considered a risk for abuse in performance horses, despite the absence of Food and Drug Administration approval for such use. Oral administration of zilpaterol to horses at the dosage indicated for use in cattle may result in prolonged adverse effects, including tachycardia, muscle tremors, and renal damage.     

Three-dimensional electroanatomic mapping and radiofrequency catheter ablation of ventricular arrhythmia in a dog without structural heart disease

A 1.5-year-old, female-spayed mix-breed dog was presented with recurrent episodes of shaking and excessive panting attributed to drug-refractory ventricular arrhythmia (VA) characterized predominantly by incessant periods of ventricular bigeminy. The VA had a narrow QRS morphology, suggestive of an origin near the His bundle or fascicular system. Diagnostic evaluation found no structural heart disease or underlying etiology. Three-dimensional electroanatomic mapping and radiofrequency catheter ablation were pursued. Voltage mapping demonstrated normal bi-ventricular voltage (≥1.5 mV) without any fractionated or multicomponent electrograms, indicating the absence of ventricular myocardial scar. Pace mapping identified an endocardial origin of the VA at the basal anterior septum of the left ventricle, distal to the His bundle and near the left bundle branch. Two ablation lesions were delivered to this site, and a left bundle branch block was temporarily induced. The dog recovered uneventfully. One month later, the owners reported a remarkable improvement in clinical signs, and follow-up 48-h Holter monitor found complete resolution of VA.     

Cardiovascular changes in horses with atrial fibrillation and high thyroid hormone concentration: a case–control study

IntroductionHyperthyroidism is a predisposing factor for atrial fibrillation (AF) in humans. The relationship between high thyroid hormone (TH) and AF in horses has not been evaluated.ObjectivesThe aim of this study is to identify whether (1) high TH concentrations were present in horses with AF, (2) other cardiovascular effects were observed in horses with high TH and AF, and (3) TH status affected recurrence rate.AnimalsTwenty-three horses presented with naturally occurring AF.MethodsProspective case–control clinical study. Thyroid hormone concentration was measured in horses presenting with AF. Heart rate, electrocardiogram, blood pressure, and an echocardiogram were recorded as part of their clinical workup. Recurrence rate was determined by owner/veterinarian follow-up.ResultsHigh TH concentration was found in 60% of horses with AF. Horses in the high TH group had a higher heart rate (P=0.001), systolic blood pressure (P=0.019), left ventricular free wall thickness (P=0.026), relative wall thickness (P=0.041) and were more likely to have periods of AF with a rapid ventricular response rate (P=0.022). All horses were successfully converted to normal sinus rhythm. The likelihood of recurrence was not different between groups.ConclusionElevated TH concentration can be found in horses with AF. Other cardiovascular effects of high TH concentrations in other species were also present in horses with AF and elevated TH concentrations. This study recommends measuring TH concentrations in horses presenting for AF with a history of thyroid or iodine supplementation. This study also cautions against TH or iodine supplementation in healthy performance horses.