A multicenter, retrospective study of cardiac disease in Borzoi dogs.

Borzoi are large, relatively uncommon sighthounds anecdotally reported to suffer from sudden death. This multicenter retrospective cohort study aimed to describe the sample of Borzoi presenting to veterinary cardiologists for evaluation, with records searched from 14 centers across a study period of up to 20 years. The study sample was comprised of 152 client-owned Borzoi, with dogs most commonly presenting for pre-breed screening in 87/152 (52%), followed by evaluation of an arrhythmia in 28/152 (18%). Of the 131/152 (86%) dogs that had an echocardiogram performed, 85/131 (65%) were structurally normal, with 40/85 (47%) structurally normal dogs having trace or mild atrioventricular valve regurgitation. Tricuspid valve dysplasia was the most commonly diagnosed congenital cardiac disease (n = 6). Myxomatous mitral valve disease (n = 12) and dilated cardiomyopathy (n = 13) were diagnosed at similar frequencies, though 92% of valve disease cases were mild. Only 48/152 (32%) Borzoi had a diagnostic electrocardiogram (ECG) and/or a Holter monitor for arrhythmia screening. Despite this, ventricular arrhythmias were identified during the entirety of the available cardiac evaluation including diagnostic ECG, contemporaneous ECG monitoring during the echocardiogram, and/or Holter monitor in 25/131 (19%) dogs in which an echocardiographic diagnosis was available. Of these 25 Borzoi, 76% had minimal or no structural cardiac disease identified, and five had a family history of sudden death. A sudden death outcome was reported in 3/55 (5%) Borzoi with long-term outcome data available. In conclusion, Borzoi commonly have trace or mild atrioventricular valve insufficiencies, and may develop ventricular arrhythmias and dilated cardiomyopathy.

Discordant Alternans as a Mechanism for Initiation of Ventricular Fibrillation In Vitro.

Background Ventricular tachyarrhythmias are often preceded by short sequences of premature ventricular complexes. In a previous study, a restitution-based computational model predicted which sequences of stimulated premature complexes were most likely to induce ventricular fibrillation in canines in vivo. However, the underlying mechanism, based on discordant-alternans dynamics, could not be verified in that study. The current study seeks to elucidate the mechanism by determining whether the spatiotemporal evolution of action potentials and initiation of ventricular fibrillation in in vitro experiments are consistent with model predictions. Methods and Results Optical mapping voltage signals from canine right-ventricular tissue (n=9) were obtained simultaneously from the entire epicardium and endocardium during and after premature stimulus sequences. Model predictions of action potential propagation along a 1-dimensional cable were developed using action potential duration versus diastolic interval data. The model predicted sign-change patterns in action potential duration and diastolic interval spatial gradients with posterior probabilities of 91.1%, and 82.1%, respectively. The model predicted conduction block with 64% sensitivity and 100% specificity. A generalized estimating equation logistic-regression approach showed that model-prediction effects were significant for both conduction block ( P<1×10-15, coefficient 44.36) and sustained ventricular fibrillation ( P=0.0046, coefficient, 1.63) events. Conclusions The observed sign-change patterns favored discordant alternans, and the model successfully identified sequences of premature stimuli that induced conduction block. This suggests that the relatively simple discordant-alternans-based process that led to block in the model may often be responsible for ventricular fibrillation onset when preceded by premature beats. These observations may aid in developing improved methods for anticipating block and ventricular fibrillation.

An accessory bypass tract masked by the presence of atrial fibrillation in a horse.

Accessory bypass tracts are rarely documented in horses. Here, we present a case of an accessory bypass tract which was initially masked by the presence of atrial fibrillation. Evidence of ventricular pre-excitation was recognized after cardioversion to normal sinus rhythm and the horse was diagnosed with Wolff-Parkinson-White Syndrome. In people, atrial fibrillation in the presence of an accessory bypass tract is considered dangerous due to the risk of sudden cardiac death. Although we did not consider this horse safe to ride, he continues to compete successfully and has not had recurrence of clinically significant tachyarrhythmias.

Combination therapy with mexiletine and sotalol suppresses inherited ventricular arrhythmias in German shepherd dogs better than mexiletine or sotalol monotherapy: a randomized cross-over study.

OBJECTIVES: To determine the spontaneous variability of ventricular arrhythmias (VA) and evaluate anti-arrhythmic efficacy of mexiletine, sotalol, and a mexiletine-sotalol combination in German shepherd dogs (GSD) with inherited arrhythmias. ANIMALS, MATERIALS AND METHODS: 12 affected GSD, median age 20 weeks, received mexiletine (8 mg/kg PO q8 h), sotalol (2.5 mg/kg PO q12 h), and combination therapy for 6 days in random order. Pre- and post-treatment 24 h Holter recordings were acquired, allowing determination of VA variability and reduction in 24 h VA for each treatment. Drug concentrations during each arm were measured. RESULTS: An anti-arrhythmic effect could be inferred if ventricular premature complexes (VPC), ventricular couplets (V(cpl)), ventricular tachycardia runs (VT(runs)) and total ventricular ectopy (VE(tot)) frequency were reduced by 61%, 97%, 98%, and 63% (1 control Holter model), by 53%, 94%, 95%, and 54% (4 control Holter model) and by 54%, 95%, 96% and 56% (3 control Holter model). Combination therapy reduced VPC and VE(tot) in more dogs (5/12 and 6/12) than mexiletine (1/11 and 2/11) or sotalol (2/9 and 1/9) (p < 0.05). The combination therapy reduced the mean number of VPC, V(cpl), and VE(tot). Sotalol monotherapy produced an increase in VT(runs). Plasma mexiletine concentration was higher during combination therapy than with monotherapy. CONCLUSIONS: Combination therapy reduced VPC in affected GSD. Sotalol monotherapy increased VT(runs). Combination therapy increased plasma mexiletine concentrations.

Clinical findings and serum cardiac troponin I concentrations in horses after intragastric administration of sodium monensin.

Six adult horses were administered sodium monensin, 1.0-1.5 mg/kg, via gastric gavage. Anorexia and/or diarrhea occurred within 24 hr after monensin administration in all 6 horses. Cardiac disease and dysfunction were evaluated by both elevations in heart rate, echocardiography, and an increase in serum concentrations of cardiac troponin I (cTnI), occurred in 4 horses. The development and severity of cardiac disease was likely affected by the monensin dose, vehicle (water or corn oil) mixed with monensin, and/or whether the monensin was administered to fed or fasted horses. Initial increases in cTnI concentrations occurred between 24 and 72 hr after monensin administration. The 2 horses with the highest cTnI concentrations died or were euthanized within 5 days after monensin administration and had severe cardiac disease. One horse had increased cTnI concentrations from day 2 to day 16, but no apparent change in ventricular contractile function was evident on echocardiography. The fourth diseased horse did not return to cTnI reference intervals until day 27 after monensin administration, and the ventricular function was still abnormal just before euthanasia 9 months later. Cardiac troponin I measurements could be useful in managing farm outbreaks of accidental monensin feeding by the early identification of horses with cardiac disease.

Evaluation of atrial fibrillation induced during anesthesia with fentanyl and pentobarbital in German Shepherd Dogs with inherited arrhythmias.

OBJECTIVE: To determine the type of atrial fibrillation induced by use of 2 pacing protocols during fentanyl and pentobarbital anesthesia before and after administration of atropine and to determine the organization of electrical activity in the left and right atria during atrial fibrillation in German Shepherd Dogs. ANIMALS: 7 German Shepherd Dogs. PROCEDURES: Extrastimulus and pacedown protocols were performed before and after atropine administration. Monophasic action potential spectral entropy and mean dominant frequency were calculated during atrial fibrillation. RESULTS: Atrial fibrillation occurred spontaneously in 6 of 7 dogs. All 7 dogs had atrial fibrillation induced. Sustained atrial fibrillation occurred in 13 of 25 (52%) episodes induced by the extrastimulus protocol and in 2 of 12 episodes of atrial fibrillation induced by pacedown. After atropine administration, sustained atrial fibrillation did not occur, and the duration of the nonsustained atrial fibrillation (6 episodes in 2 dogs of 1 to 26 seconds) was significantly shorter than before atropine administration (25 episodes in 7 dogs of 1 to 474 seconds). The left atrium (3.67 +/- 0.08) had lower spectral entropy than the right atrium (3.81 +/- 0.03), indicating more electrical organization in the left atrium. The mean dominant frequency was higher in the left atrium in 3 dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Atrial fibrillation developed spontaneously and was induced in German Shepherd Dogs under fentanyl and pentobarbital anesthesia. Electrical activity was more organized in the left atrium than in the right atrium as judged by use of spectral entropy.

Dynamic mechanism for initiation of ventricular fibrillation in vivo.

BACKGROUND: Dynamically induced heterogeneities of repolarization may lead to wave-front destabilizations and initiation of ventricular fibrillation (VF). In a computer modeling study, we demonstrated that specific sequences of premature stimuli maximized dynamically induced spatial dispersion of refractoriness and predisposed the heart to the development of conduction block. The purpose of this study was to determine whether the computer model results pertained to the initiation of VF in dogs in vivo. METHODS AND RESULTS: Monophasic action potentials were recorded from right and left ventricular endocardium in anesthetized beagle dogs (n=11) in vivo. Restitution of action potential duration and conduction time and the effective refractory period after delivery of the basic stimulus (S(1)) and each of 3 premature stimuli (S(2), S(3), S(4)) were determined at baseline and during verapamil infusion. The effective refractory period data were used to determine the interstimulus intervals for a sequence of 4 premature stimuli (S(2)S(3)S(4)S(5)=CL(VF)) for which the computer model predicted maximal spatial dispersion of refractoriness. Delivery of CL(VF) was associated with discordant action potential duration alternans and induction of VF in all dogs. Verapamil decreased spatial dispersion of refractoriness by reducing action potential duration and conduction time restitution in a dose-dependent fashion, effects that were associated with reduced inducibility of VF with CL(VF). CONCLUSIONS: Maximizing dynamically induced spatial dispersion of repolarization appears to be an effective method for inducing VF. Reducing spatial dispersion of refractoriness by modulating restitution parameters can have an antifibrillatory effect in vivo.

Molecular composition of the intercalated disc in a spontaneous canine animal model of arrhythmogenic right ventricular dysplasia/cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by ventricular arrhythmias, sudden death, and fatty or fibrofatty replacement of right ventricular myocytes. Recent studies have noted an association between human ARVD/C and molecular remodeling of intercalated disc structures. However, progress has been constrained by limitations inherent to human studies. OBJECTIVE: We studied the molecular composition of the intercalated disc structure in a naturally occurring animal model of ARVD/C (Boxer dogs). METHODS: We studied hearts from 12 Boxers with confirmed ARVD/C and 2 controls. Ventricular sections from 4 animals were examined by immunofluorescent microscopy. Frozen tissue samples were used for Western blot analysis. Proteins investigated were N-cadherin, plakophilin 2, desmoplakin, plakoglobin, desmin, and connexin 43 (Cx43). RESULTS: In control dogs, all proteins tested by immunofluorescence analysis yielded intense localized signals at sites of end-to-end cell apposition. In contrast, myocardial tissues from ARVD/C-afflicted Boxers showed preservation of N-cadherin staining but loss of detectable signal for Cx43 at the intercalated disc location. Western blots indicated that the Cx43 protein was still present in the samples. Gene sequencing analysis showed no mutations in desmoplakin, plakoglobin, Cx43, or plakophilin 2. CONCLUSION: Mutation(s) responsible for ARVD/C in Boxers lead, directly or indirectly, to severe modifications of mechanical and electrical cell-cell interactions. Furthermore, significant reduction in gap junction formation may promote a substrate for malignant ventricular arrhythmias. This model may help to advance our understanding of the molecular basis, pathophysiology, and potential therapeutic approach to patients with ARVD/C.

Complete atrioventricular canal defect in a foal: Clinical and pathological features.

Atrioventricular (AV) canal defects comprise a rare category of congenital heart disease associated with abnormal development of the endocardial cushions. These anomalies include a broad spectrum of lesions involving the atrial septum primum, the inlet portion of the ventricular septum, and the atrioventricular valves. In severe cases heart failure may result. The present report describes cardiopulmonary findings in a six-week-old, female Thoroughbred foal with persistent tachypnea and tachycardia since birth. Clinical, echocardiographic, cardiac catheterization, and pathologic findings were compatible with complete AV canal defect with bi-directional shunting, congestive heart failure, and pulmonary hypertension. Gross cardiac pathologic findings included a large atrioventricular septal defect, a common atriovalvular orifice, five atrioventricular leaflets, with two free-floating bridging leaflets. Histopathologic lesions in the lung included hypertrophy of the pulmonary arteriolar walls due to thickening of the tunica media. This represents a well documented case of complete endocardial cushion defect with anomalous development of the atrioventricular valves and resultant pulmonary hypertension and heart failure.

Defibrillation of German shepherds with inherited ventricular arrhythmias and sudden death.

OBJECTIVE: To characterize defibrillation success in German shepherd (GS) dogs with inherited ventricular arrhythmias and sudden death. BACKGROUND: Ventricular tachycardia (VT) degenerates to ventricular fibrillation (VF) as the cause of death in GS dogs. To test the hypothesis that GS dogs are more difficult to defibrillate than other dogs, we sought to compare defibrillation success of induced VF in affected GS dogs to a control group of beagles. METHODS: ECG and monophasic action potential (MAP) recordings were acquired during VF and transthoracic defibrillation in anesthetized GS dogs (n=13) and normal beagles (n=7). Shock efficacy, energy requirements, VF frequency and post-defibrillation rhythms were compared between the 2 groups. RESULTS: First shock success of all episodes of VF was lower in GS dogs (10 of 18) than beagles (46 of 47) (p<0.0001). However, when evaluated by dog, shock success was not different between GS and beagles (7 of 13 and 6 of 7, respectively; p=0.15). Multiple shock success (

Cardioversion with lidocaine of vagally associated atrial fibrillation in two dogs.

Two dogs with acute onset atrial fibrillation (AF) were cardioverted to sinus rhythm by the administration of 2mg/kg lidocaine given intravenously. Each dog was believed to have AF initiated because of elevated vagal tone. This report has potential clinical impact for a subset of dogs because it offers a treatment to circumvent persistent AF. Furthermore, this encouraging result of a pharmacologic cardioversion suggests that further investigation would be of interest to ascertain the effectiveness and mechanism of the antiarrhythmic action of lidocaine in vagally induced AF.

Effects of acute systemic endothelin receptor blockade on cardiac electrophysiology in vivo.

BQ-123, a selective endothelin-A receptor antagonist, has been demonstrated to suppress arrhythmias. However, the role of physiologic levels of endogenous endothelin-1 (ET-1) with respect to electrophysiologic properties of the heart is unknown. BQ-123 (0.45, 0.9, 1.8, 3.6, 7.2, and 14.4 microg/kg/min; n = 10) or saline (control, n = 5) was administered IV for 15 minutes of continuous-rate infusion at incremental doses to anesthetized normal pigs. BQ-123 had no effect on PR and QT interval, QRS duration, intraatrial and AV nodal conduction time as well as the atrial, AV nodal, and ventricular effective refractory periods. As compared with baseline, BQ-123 at 7.2 and 14.4 microg/kg/min caused an increase in heart rate (99 +/- 17 versus 110 +/- 14 and 118 +/- 14 bpm, respectively; P < 0.05), shortened sinus node recovery time (818 +/- 165 versus 641 +/- 69 and 609 +/- 74 milliseconds, respectively; P < 0.05) and decreased mean arterial pressure at 14.4 microg/kg/min (95 +/- 18 versus 80 +/- 11 mm Hg; P < 0.05). We conclude that in the normal pig, physiologic levels of ET-1 have no effect on conduction properties of atrial, AV nodal, or Purkinje fibers. However, antagonism of ET-1 by BQ-123 unmasks the effect of ET-1 on maintenance of vasomotor tone, which in turn may affect heart rate and sinus node automaticity in the intact pig.

Management of atrial fibrillation.

Atrial fibrillation (AF) is the most common clinically important arrhythmia in veterinary medicine. Electrical cardioversion of AF to sinus rhythm is feasible, but pharmacologic rate control is an effective and achievable treatment strategy for most veterinary patients. Recent human trials suggest that rate control and rhythm control are almost equally beneficial. Nevertheless, AF can be a challenging arrhythmia to manage, because most affected animal shave numerous other concurring problems associated with the underlying heart disease that dictate or influence the clinician's choice of treatment and monitoring strategy for each patient.