Objective—To determine whether Boxers with a clinical
diagnosis of arrhythmogenic right ventricular cardiomyopathy
(ARVC) have increased plasma concentrations
of brain natriuretic peptide (BNP), compared
with concentrations in clinically normal dogs.
Animals—13 Boxers with ARVC, 9 clinically normal
Boxers, 10 clinically normal non-Boxer dogs, and 5
hound dogs with systolic dysfunction.
Procedure—All Boxers were evaluated via 24-hour
ambulatory electrocardiography and echocardiography;
the number of ventricular premature contractions
(VPCs) per 24 hours was assessed. Hound
dogs with cardiac pacing-induced systolic dysfunction
(positive control dogs) and clinically normal non-Boxer
dogs (negative control dogs) were evaluated
echocardiographically. Three milliliters of blood was
collected from each dog for measurement of plasma
BNP concentration by use of a radioimmunoassay.
Results—Mean ± SD plasma BNP concentration for
the ARVC-affected Boxers, clinically normal Boxers,
negative control dogs, and positive control dogs was
11.0 ± 4.6 pg/mL, 7.9 ± 3.2 pg/mL, 11.5 ± 4.9 pg/mL,
and 100.8 ± 56.8 pg/mL, respectively. Compared with
findings in the positive control group, plasma BNP
concentration in each of the other 3 groups was significantly
different. There was no significant difference
in BNP concentration between the 2 groups of
Boxers. A significant correlation between plasma BNP
concentration and number of VPCs per 24 hours in
the ARVC-affected Boxers was not identified.
Conclusions and Clinical Relevance—A significant
difference in BNP concentration between Boxers with
ARVC and clinically normal Boxers was not identified.
Results suggest that BNP concentration may not be
an indicator of ARVC in Boxers. (Am J Vet Res
Objective—To use an index of myocardial performance (IMP) to assess right ventricular function in Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC).
Animals—22 Boxers (12 Boxers with ARVC diagnosed by the detection of ≥ 1,000 ventricular premature complexes (VPCs)/24 h and 10 Boxers with ≤ 5 VPCs/24 h (control dogs).
Procedures—Pulsed-wave Doppler recordings of tricuspid inflow and pulmonic outflow were acquired. Preejection period (PEP), ejection time (ET), PEP/ET, and IMP were determined for the right ventricle by use of data from separate cardiac cycles.
Results—A significant difference was not identified between groups for right ventricular PEP, right ventricular ET, right ventricular PEP/ET, or right ventricular IMP. Right ventricular IMP was not significantly correlated with VPC number (r = 0.21) or VPC grade (r = −0.3) in Boxers with ARVC.
Conclusions and Clinical Relevance—Boxers with ARVC did not have significant differences in right ventricular IMP, compared with results for control Boxers. This would suggest that right ventricular dysfunction does not develop in Boxers with ARVC or that a more severe phenotype of the disease may be necessary for detection of dysfunction. Additional studies that use more sensitive techniques to evaluate myocardial function may be warranted.
Objective—To sequence the exonic and splice site regions of the 4 desmosomal genes associated with the human form of familial arrhythmogenic right ventricular cardiomyopathy (ARVC) in Boxers with ARVC and identify a causative mutation.
Animals—10 unrelated Boxers with ARVC and 2 unaffected Labrador Retrievers (control dogs).
Procedures—Exonic and splice site regions of the 4 genes encoding the desmosomal proteins plakophilin-2, plakoglobin, desmoplakin, and desmoglein-2 were sequenced. Sequences were compared for nucleotide sequence changes between affected dogs and the published sequences for clinically normal dogs and between affected dogs and the control dogs. Base-pair changes were considered to be causative for ARVC if they were detected in an affected dog but not in unaffected dogs, and if they involved a conserved amino acid and changed that amino acid to one of a different polarity, acid-base status, or structure.
Results—A causative mutation for ARVC in Boxers was not identified, although single nucleotide polymorphisms were detected in some affected dogs within exon 3 of the plakophilin-2 gene; exon 3 of the plakoglobin gene; exons 3 and 7 of the desmoglein-2 gene; and exons 6, 14, 15, and 24 of the desmoplakin gene. None of these changed the amino acid of the respective protein.
Conclusions and Clinical Relevance—Mutations within the desmosomal genes associated with the development of ARVC in humans do not appear to be causative for ARVC in Boxers. Genomewide scanning for genetic loci of interest in dogs should be pursued.
Objective—To sequence the exonic and splice site regions of 5 cardiac genes associated with the human form of familial dilated cardiomyopathy (DCM) in Doberman Pinschers with DCM and to identify a causative mutation.
Animals—5 unrelated Doberman Pinschers with DCM and 2 unaffected Labrador Retrievers (control dogs).
Procedures—Exonic and splice site regions of the 5 genes encoding the cardiac proteins troponin C, lamin A/C, cysteine- and glycine-rich protein 3, cardiac troponin T, and the β-myosin heavy chain were sequenced. Sequences were compared for nucleotide changes between affected dogs and the published canine sequences and 2 control dogs. Base pair changes were considered to be causative for DCM if they were present in an affected dog but not in the control dogs or published sequences and if they involved a conserved amino acid and changed that amino acid to a different polarity, acid-base status, or structure.
Results—A causative mutation for DCM in Doberman Pinschers was not identified, although single nucleotide polymorphisms were detected in some dogs in the cysteine- and glycine-rich protein 3, β-myosin heavy chain, and troponin T genes.
Conclusions and Clinical Relevance—Mutations in 5 of the cardiac genes associated with the development of DCM in humans did not appear to be causative for DCM in Doberman Pinschers. Continued evaluation of additional candidate genes or a focused approach with an association analysis is warranted to elucidate the molecular cause of this important cardiac disease in Doberman Pinschers.
Objective—To evaluate serum cardiac troponin I (cTnI) concentrations in Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC), unaffected (control) Boxers, and control non-Boxers.
Animals—10 Boxers with a clinical diagnosis of ARVC defined by ≥ 1,000 ventricular premature complexes (VPCs)/24 h on an ambulatory ECG, 10 control Boxers assessed as normal by the presence of < 5 VPCs/24h, and 10 control non-Boxers.
Procedures—Serum was extracted from a blood sample from each dog. Analysis of serum cTnI concentrations was performed.
Results—Mean ± SD serum cTnI concentration was 0.142 ± 0.05 ng/mL for Boxers with ARVC, 0.079 ± 0.03 ng/mL for control Boxers, and 0.023 ± 0.01 ng/mL for control non-Boxers. A significant difference in serum cTnI concentrations was observed among the 3 groups. In the combined Boxer population (ie, Boxers with ARVC and control Boxers), a significant correlation was found between serum cTnI concentration and number of VPCs/24 h (r = 0.78) and between serum cTnI concentration and grade of ventricular arrhythmia (r = 0.77).
Conclusions and Clinical Relevance—Compared with clinically normal dogs, Boxers with ARVC had a significant increase in serum cTnI concentration. For Boxers, correlations were found between serum cTnI concentration and number of VPCs/24 h and between concentration and the grade of arrhythmia. Because of the overlap in serum cTnI concentrations in control Boxers and Boxers with ARVC, future studies should evaluate the correlation of serum cTnI concentration with severity of disease in terms of degree of myocardial fibrofatty changes.
Objective—To compare plasma fatty acid concentrations and the relationships of fatty acids to arrhythmias in Boxers versus Doberman Pinschers.
Animals—38 Boxers and 13 Doberman Pinschers.
Procedures—Boxers and Doberman Pinschers evaluated via Holter recording and for which a blood sample was available were included. Echocardiograms were performed in 49 of 51 dogs. The number of ventricular premature complexes (VPCs)/24 h was counted and fatty acids analyzed. Plasma fatty acid concentrations and VPCs/24 h, as well as correlations between the 2 variables, were compared between the 2 breeds.
Results—Compared with the Doberman Pinschers, Boxers had significantly higher plasma concentrations of γ-linolenic acid but lower concentrations of arachidonic acid. Total n-6 fatty acids and total polyunsaturated fatty acid concentrations were higher in Doberman Pinschers. There were significant, but weak, positive correlations between VPCs and oleic acid, total n-3 fatty acids, and total n-9 fatty acids in Boxers but not in Doberman Pinschers.
Conclusions and Clinical Relevance—Data suggested that plasma fatty acid concentrations may differ between Boxers and Doberman Pinschers and that the relationship between fatty acid concentrations and VPCs may be different between these 2 breeds.
OBJECTIVE To identify cardiac tissue genes and gene pathways differentially expressed between dogs with and without dilated cardiomyopathy (DCM).
ANIMALS 8 dogs with and 5 dogs without DCM.
PROCEDURES Following euthanasia, samples of left ventricular myocardium were collected from each dog. Total RNA was extracted from tissue samples, and RNA sequencing was performed on each sample. Samples from dogs with and without DCM were grouped to identify genes that were differentially regulated between the 2 populations. Overrepresentation analysis was performed on upregulated and downregulated gene sets to identify altered molecular pathways in dogs with DCM.
RESULTS Genes involved in cellular energy metabolism, especially metabolism of carbohydrates and fats, were significantly downregulated in dogs with DCM. Expression of cardiac structural proteins was also altered in affected dogs.
CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that RNA sequencing may provide important insights into the pathogenesis of DCM in dogs and highlight pathways that should be explored to identify causative mutations and develop novel therapeutic interventions.
Objective—To determine whether plasma concentrations
of tumor necrosis factor-α (TNF-α) are increased
in cats with congestive heart failure (CHF) secondary
Animals—26 adult cats with CHF and cardiomyopathy
and 9 healthy control cats.
Procedure—Plasma concentrations of TNF-α were
measured in cats with CHF and cardiomyopathy.
Tumor necrosis factor-α was measured by quantifying
cytotoxic effects of TNF-α on L929 murine fibrosarcoma
Results—Concentrations of TNF-α were increased
(0.13 to 3.6 U/ml) in 10 of 26 cats with CHF but were
undetectable in the other 16 cats with CHF and all
control cats. In 20 of 26 cats with CHF, right-sided
heart failure (RHF) was evident; TNF-α concentrations
were increased in 9 of these 20 cats. The remaining 6
cats had left-sided heart failure (LHF); TNF-α concentrations
were increased in only 1 of these cats. Age of
cats with LHF (mean ± SD, 12.1 ± 6.2 years) was not
significantly different from age of the cohort with RHF
(10.5 ± 5.2 years). Body weight of cats with increased
TNFα concentrations (5.4 ± 1.8 kg) was not significantly
different from body weight of cats with CHF
that did not have measurable concentrations of TNF-α
(4.7 ± 1.6 kg).
Conclusionss and Clinical Relevance—Concentrations
of TNF-α were increased in many cats with
CHF. Cats with RHF were most likely to have
increased TNF-α concentrations. Increased plasma
concentrations of TNF-α in cats with CHF may offer
insights into the pathophysiologic mechanisms of
heart failure and provide targets for therapeutic interventions.
(Am J Vet Res 2002;63:640–642)
Objective—To determine electrocardiographic parameters
in healthy llamas and alpacas.
Animals—23 llamas and 12 alpacas.
Procedure—Electrocardiography was performed in
nonsedated standing llamas and alpacas by use of multiple
simultaneous lead recording (bipolar limb, unipolar
augmented limb, and unipolar precordial leads).
Results—Common features of ECGs of llamas and
alpacas included low voltage of QRS complexes, variable
morphology of QRS complexes among camelids,
and mean depolarization vectors (mean electrical
axes) that were directed dorsocranially and to the
right. Durations of the QT interval and ST segment
were negatively correlated with heart rate.
Conclusions and Clinical Relevance—ECGs of
acceptable quality can be consistently recorded in
nonsedated standing llamas and alpacas. Features of
ECGs in llamas and alpacas are similar to those of other
ruminants. Changes in the morphology of the QRS
complexes and mean electrical axis are unlikely to be
sensitive indicators of ventricular enlargement in llamas
and alpacas. (Am J Vet Res 2004;65:1719–1723)
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)