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- Author or Editor: Kathryn M. Meurs x
- Cardiovascular System x
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Abstract
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.
Abstract
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.
Abstract
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.
Abstract
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.
Abstract
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.
Abstract
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.
