Efficacy of Benazepril Hydrochloride to Delay the Progression of Occult Dilated Cardiomyopathy in Doberman Pinschers

Background: Angiotensin converting enzyme inhibitors (ACEIs) are recommended in people to treat asymptomatic (occult) dilated cardiomyopathy (DCM). Efficacy of therapy in occult DCM in dogs is unknown.
Hypothesis: ACEIs, specifically benazepril hydrochloride (BH), will delay the onset of overt DCM in Doberman Pinschers.
Animals: Ninety-one Doberman Pinschers were studied, 57 dogs received BH, and 34 dogs no ACEI.
Methods: Retrospective study of the medical records of all Doberman Pinschers with occult DCM that received BH or no ACEI between April 1989 and February 2003. Two criteria of left ventricular enlargement were used for enrollment: one independent of body weight (BW) (C1) and the other indexed to BW (C2). Cox proportional hazards analyses were used to identify variables associated with the onset of overt DCM.
Results: On univariate analysis the median time to onset of overt DCM was significantly longer for the benazepril group (for C1: 425 days for BH, 95% confidence interval [CI] 264–625 days; 339 days for no ACEI, CI 172–453 days, P = .02; for C2: 454 days for BH, CI 264–628 days; 356 days for no ACEI, CI 181–547 days, P = .02). The hazard ratio (HR) (benazepril/no ACEI) was 0.57, CI 0.35–0.94, P = .03 for C1; HR = 0.56, CI 0.34–0.93, P = .02 for C2. On multivariate analysis, BH significantly delayed onset of overt DCM (HR [benazepril/no ACEI] = 0.45, CI 0.26–0.78, P < .01, for C1; HR = 0.36, CI 0.21–0.63, P < .01, for C2).
Conclusions: BH in particular and ACEIs in general might delay the progression of occult DCM. Prospective studies are warranted to test this theory.     

Molecular evaluation of five cardiac genes in Doberman Pinschers with dilated cardiomyopathy

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 beta-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, beta-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.     

Evaluation of the cardiac actin gene in Doberman Pinschers with dilated cardiomyopathy

OBJECTIVE: To evaluate the coding region of the cardiac actin gene in Doberman Pinschers with dilated cardiomyopathy (DCM) for mutations that could be responsible for the development of the condition ANIMALS: 28 dogs (16 Doberman Pinschers with DCM and 12 mixed-breed control dogs). PROCEDURE: Ten milliliters of blood was collected from each dog for DNA extraction. Polymerase chain reaction (PCR) primers were designed to amplify canine exonic regions, using the sequences of exons 2 to 6 of the cardiac actin gene. Single-stranded conformational polymorphism analysis was performed for each exon with all samples. Autoradiographs were analyzed for banding patterns specific to affected dogs. The DNA sequencing was performed on a selected group of affected and control dogs. RESULTS: Molecular analysis of exons 2 to 6 of the cardiac actin gene did not reveal any differences in base pairs between affected dogs and control dogs selected for DNA evaluation. CONCLUSIONS: Mutations in exons 5 and 6 of the cardiac actin gene that have been reported in humans with familial DCM do not appear to be the cause of familial DCM in Doberman Pinschers. Additionally, evaluation of exons 2 to 6 for causative mutations did not reveal a cause for inherited DCM in these Doberman Pinschers. Although there is evidence that DCM in Doberman Pinschers is an inherited problem, a molecular basis for this condition remains unresolved. Evaluation of other genes coding for cytoskeletal proteins is warranted.     

Positive Coombs' test results in two dogs treated with amiodarone

Effects of amiodarone, an antiarrhythmic drug that is effective in suppressing severe ventricular arrhythmias that are refractory to other antiarrhythmic drugs, were evaluated in 2 dogs with cardiac disease. One dog was a Doberman Pinscher with cardiomyopathy that developed severe thrombocytopenia after receiving amiodarone for 7 months. The second was a Giant Schnauzer with acquired mitral valve degeneration that developed regenerative anemia after receiving amiodarone for 5 months. Results of direct Coombs' tests were positive in both dogs. Adverse effects of amiodarone are numerous; in dogs, the most common adverse effects are anorexia and hepatotoxicosis. Frequent CBC and serum biochemical analyses should be performed when amiodarone is administered with the intent of continuing the drug indefinitely.     

Effect of pimobendan on case fatality rate in Doberman Pinschers with congestive heart failure caused by dilated cardiomyopathy

BACKGROUND: Despite traditional therapy of a diuretic, angiotensin converting enzyme inhibitor, digoxin, or a combination of these drugs, survival of dogs with dilated cardiomyopathy (DCM) is low. Pimobendan, an inodilator, has both inotropic and balanced peripheral vasodilatory properties. HYPOTHESIS: Pimobendan when added to conventional therapy will improve morbidity and reduce case fatality rate in Doberman Pinschers with congestive heart failure (CHF) caused by DCM. ANIMALS: Sixteen Doberman Pinschers in CHF caused by DCM. METHODS: A prospective randomized, double-blind, placebo-controlled study with treatment failure as the primary and quality of life (QoL) indices as secondary outcome variables. Therapy consisted of furosemide (per os [PO] as required) and benazepril hydrochloride (0.5 mg/kg PO q12h) and dogs were randomized in pairs and by sex to receive pimobendan (0.25 mg/kg PO q12h) or placebo (1 tablet PO q12h). RESULTS: Pimobendan-treated dogs had a significant improvement in time to treatment failure (pimobendan median, 130.5 days; placebo median, 14 days; P= .002; risk ratio = 0.35, P= .003, lower 5% confidence limit = 0.13, upper 95% confidence limit = 0.71). Number and rate of dogs reaching treatment failure in the placebo group precluded the analysis of QoL. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan should be used as a first-line therapeutic in Doberman Pinschers for the treatment of CHF caused by DCM.     

Evaluation of the phospholamban gene in purebred large-breed dogs with dilated cardiomyopathy

OBJECTIVE: To evaluate the role of the phospholamban gene in purebred large-breed dogs with dilated cardiomyopathy (DCM). ANIMALS: 6 dogs with DCM, including 2 Doberman Pinschers, 2 Newfoundlands, and 2 Great Danes. PROCEDURE: All dogs had clinical signs of congestive heart failure, and a diagnosis of DCM was made on the basis of echocardiographic findings. Blood samples were collected from each dog, and genomic DNA was isolated by a salt extraction method. Specific oligonucleotides were designed to amplify the promoter, exon 1, the 5'-part of exon 2 including the complete coding region, and part of intron 1 of the canine phospholamban gene via polymerase chain reaction procedures. These regions were screened for mutations in DNA obtained from the 6 dogs with DCM. RESULTS: No mutations were identified in the promoter, 5' untranslated region, part of intron 1, part of the 3' untranslated region, and the complete coding region of the phospholamban gene in dogs with DCM. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that mutations in the phospholamban gene are not a frequent cause of DCM in Doberman Pinschers, Newfoundlands, and Great Danes.     

Prevalence of Dilated Cardiomyopathy in Doberman Pinschers in Various Age Groups

Background: Dilated cardiomyopathy (DCM) in Doberman Pinschers is an autosomal dominant inherited disease. The prevalence of DCM in Doberman Pinschers of various age groups in Europe is currently unknown, but this information would be important to develop recommendations for screening programs. Objectives: To evaluate the prevalence of cardiomyopathy in various age groups of Dobermans. Animals: Seven hundred and seventy‐five examinations in 412 Doberman Pinschers. Methods: Dogs were included in a prospective longitudinal cohort study. Each examination included echocardiography and 24‐hour ECG (Holter) examination. A cut‐off value of >100 ventricular premature contractions (VPCs) per 24 hours on Holter examination or abnormal echocardiography was considered diagnostic for cardiomyopathy. The cumulative prevalence included all dogs with DCM and healthy dogs >7 years of age. Results: DCM prevalence in various age groups was as follows: age group 1 (1 to <2 years) 3.3%, age group 2 (2 to <4 years) 9.9%, age group 3 (4 to <6 years) 12.5%, age group 4 (6 to <8 years) 43.6%, and age group 5 (>8 years) 44.1%. The cumulative prevalence of Doberman Pinscher cardiomyopathy was 58.2%. There was an equal sex distribution, but male dogs showed earlier echocardiographic changes than did female dogs, which had significantly more VPCs. Conclusions and Clinical Importance: The prevalence of Doberman cardiomyopathy is very high in Europe. Disease manifestation and progression are different between male and female dogs. Yearly screening for DCM by Holter examination and echocardiography is recommended, starting at 2 years of age.     

Use of Simpson's Method of Disc to Detect Early Echocardiographic Changes in Doberman Pinschers with Dilated Cardiomyopathy

Background: M‐mode is the echocardiographic gold standard to diagnose dilated cardiomyopathy (DCM) in dogs, whereas Simpson's method of discs (SMOD) is the preferred method to detect echocardiographic evidence of disease in humans. Objectives: To establish reference values for SMOD and to compare those with M‐mode measurements. Animals: Nine hundred and sixty‐nine examinations of 471 Doberman Pinschers. Methods: Using a prospective longitudinal study design. Reference values for SMOD were established using 75 healthy Doberman Pinschers >8 years old with <50 ventricular premature contractions (VPCs) in 24 hours. The ability of the new SMOD cut‐off values, normalized to body surface area (BSA), for left ventricular end‐diastolic volume (LVEDV/BSA >95 mL/m²) and end‐systolic volume (LVESV/BSA > 55 mL/m²) to detect echocardiographic changes in Doberman Pinschers with DCM was compared with currently recommended M‐mode values. Dogs with elevated SMOD values but normal M‐mode measurements were followed‐up using a prospective longitudinal study design. Results: At the final examination 175 dogs were diagnosed with DCM according to both methods (M‐mode and SMOD). At previous examinations, M‐mode values were abnormal in 142 examinations only, whereas all 175 SMOD already had detected changes. Additionally, 19 of 154 dogs with >100 VPCs/24 hours and normal M‐mode values had abnormal SMOD measurement. Six dogs with increased SMOD measurements remained healthy at several follow‐up examinations (classified as false positive); in 24 dogs with increased SMOD measurements, no follow‐up examinations were available (classified as unclear). Conclusions and Clinical Importance: SMOD measurements are superior to M‐mode to detect early echocardiographic changes in Dobermans with occult DCM.     

Cardiac Troponin I in Doberman Pinschers with Cardiomyopathy

Background: Cardiac troponin I (cTnI) is useful for detection of cardiac myocyte damage, but its efficacy in detecting various stages of dilated cardiomyopathy (DCM) in Doberman Pinschers is unclear. Objectives: To evaluate the diagnostic value of cTnI in various stages of DCM in Dobermans. Animals: Six hundred and fifty‐three cTnI measurements of 336 Doberman Pinschers. Methods: Using a longitudinal study design, staging of the disease was based upon 24‐hour‐ambulatory‐ECG (Holter) and echocardiography. A total of 447 cTnI measurements were performed in 264 healthy Dobermans, and 206 cTnI measurements in 75 Dobermans with cardiomyopathy. Eighty‐eight cTnI samples were from dogs with >100 ventricular premature contractions (VPCs)/24 hour, but without echocardiographic changes (“VPC group”). Additional 19 samples originated from dogs with only echocardiographic changes (“ECHO group”), and 56 samples from dogs with both VPCs and echocardiographic changes (“VPC plus ECHO group”). Twenty samples were from dogs with clinical signs (“clinical group”). The group “incipient” included 23 dogs, that were considered to be normal according to Holter and echocardiography at the time of the exam, but that developed DCM within 1.5 years. Results: cTnI values of dogs in all disease groups, including the “incipient” (0.30 ± 0.20) and “VPC group” (0.36 ± 0.34), were significantly (P= .04, P < .001) higher than the control group (0.07 ± 0.16). A cut‐off value of >0.22 ng/mL had a sensitivity of 79.5% and a specificity of 84.4% to detect all forms of cardiomyopathy. Conclusions and Clinical Importance: cTnI measurement is a valuable diagnostic test that can detect cardiomyopathy in dogs that are otherwise clinically normal.     

Morphologic and morphometric magnetic resonance imaging features of Doberman Pinschers with and without clinical signs of cervical spondylomyelopathy

OBJECTIVE: To compare morphologic and morphometric features of the cervical vertebral column and spinal cord of Doberman Pinschers with and without clinical signs of cervical spondylomyelopathy (CSM; wobbler syndrome) detected via magnetic resonance imaging (MRI). ANIMALS: 16 clinically normal and 16 CSM-affected Doberman Pinschers. PROCEDURES: For each dog, MRI of the cervical vertebral column (in neutral and traction positions) was performed. Morphologically, MRI abnormalities were classified according to a spinal cord compression scale. Foraminal stenosis and intervertebral disk degeneration and protrusion were also recorded. Morphometric measurements of the vertebral canal and spinal cord were obtained in sagittal and transverse MRI planes. RESULTS: 4 of 16 clinically normal and 15 of 16 CSM-affected dogs had spinal cord compression. Twelve clinically normal and all CSM-affected dogs had disk degeneration. Foraminal stenosis was detected in 11 clinically normal and 14 CSM-affected dogs. Vertebral canal and spinal cord areas were consistently smaller in CSM-affected dogs, compared with clinically normal dogs. In neutral and traction positions, the intervertebral disks of CSM-affected dogs were wider than those of clinically normal dogs but the amount of disk distraction was similar between groups. CONCLUSIONS AND CLINICAL RELEVANCE: The incidence of intervertebral disk degeneration and foraminal stenosis in clinically normal Doberman Pinschers was high; cervical spinal cord compression may be present without concurrent clinical signs. A combination of static factors (ie, a relatively stenotic vertebral canal and wider intervertebral disks) distinguished CSM-affected dogs from clinically normal dogs and appears to be a key feature in the pathogenesis of CSM.     

Histologic characterization of canine dilated cardiomyopathy

Dilated cardiomyopathy (DCM), characterized by chamber dilatation and myocardial systolic and diastolic dysfunction, is one of the most common heart diseases in dogs. The clinical diagnosis is based on findings on echocardiographic and Doppler examinations, with the active exclusion of other acquired or congenital heart diseases. However, the echocardiographic criteria for the diagnosis of DCM are not wholly specific for the disease, and histologic examination may be necessary for final diagnosis. Review of reports on histologic findings in dogs with clinically diagnosed DCM reveals two histologically distinct forms of DCM: 1) cardiomyopathy of Boxers and Doberman Pinschers, corresponding to the "fatty infiltration-degenerative" type and 2) the form seen in many giant, large-, and medium-sized breeds, including some Boxers and Doberman Pinschers, classified as the "attenuated wavy fiber" type of DCM. The histologic changes of the attenuated wavy fiber type of DCM may precede clinical and echocardiographic signs of heart disease, thus indicating an early stage of DCM.     

Morphometric dimensions of the caudal cervical vertebral column in clinically normal Doberman Pinschers, English Foxhounds and Doberman Pinschers with clinical signs of disk-associated cervical spondylomyelopathy

Client-owned, clinically normal Doberman Pinschers (n=20), English Foxhounds (n=17), and Doberman Pinschers with clinical signs of disk-associated cervical spondylomyelopathy (DA-CSM) (n=17) were prospectively studied. All dogs underwent magnetic resonance imaging (MRI) of the cervical vertebral column. To evaluate vertebral canal stenosis, the canal occupying ratios of the spinal cord and cerebrospinal fluid (CSF)-column were calculated from C5 to C7. To evaluate the degree of spinal cord compression and the amount of canal compromise, the compression ratio, remaining spinal cord and CSF-column area, and vertebral canal and dorsoventral vertebral canal compromise ratios were calculated at the site of most severe compression. For each canal occupying ratio, there was a significant higher value (implicating less space available for the spinal cord in the vertebral canal) at the level of C7 for clinically affected Doberman Pinschers compared with clinically normal English Foxhounds. The remaining spinal cord area was significantly smaller in dogs with clinically relevant spinal cord compression compared to dogs with clinically irrelevant spinal cord compression. Relative stenosis of the caudal cervical vertebral canal occurred more often in Doberman Pinschers with DA-CSM compared to English Foxhounds and a critical degree of spinal cord compression should be reached to result in clinical signs.     

Assessment of mechanical ventricular synchrony in Doberman Pinschers with dilated cardiomyopathy

Objectives

Loss of temporal synchrony of myocardial contraction has been shown to reduce systolic function and be responsible for disease progression in people. The objective of this study is the assessment of inter- and intra ventricular synchrony in healthy Doberman Pinschers and those with dilated cardiomyopathy (DCM) by use of conventional Doppler and tissue velocity imaging.

Animals

A total of 60 scans from 35 client-owned Doberman Pinschers presented for cardiac evaluation were analysed.

Methods

Retrospective analysis of data. Using the European Society of Veterinary Cardiology DCM taskforce scoring system, Doberman Pinschers were classified into 4 groups: Control (Group 1; n = 12), depressed systolic function other than DCM (Group 2; n = 9), preclinical DCM (Group 3; n = 8) and symptomatic DCM (Group 4; n = 6). The time intervals between the beginning of the QRS complex and the peak velocity of pulmonic flow (Q-P) and the peak aortic flow (Q-Ao) were used to assess global synchrony between both ventricles. The time intervals between the beginning of the QRS complex and the peak myocardial systolic velocity (Q-peak S) and the onset of myocardial systolic velocity (Q-start S) were measured at the base of the right and left ventricular free wall (RVFW and LVFW) and interventricular septum (IVS), and used to determine segmental longitudinal inter- and intra ventricular synchrony.

Results

No significant loss of global or segmental longitudinal inter- or intra ventricular synchrony was identified between the groups.

Conclusion

Impairment of longitudinal fibre synchrony does not appear to be significantly associated with clinical status of DCM in Doberman Pinschers, although it was identified in certain individuals.     

Results of ambulatory electrocardiography in overtly healthy Doberman Pinschers with echocardiographic abnormalities

OBJECTIVE: To identify, by means of 24-hour ambulatory electrocardiography, electrocardiographic abnormalities in overtly healthy Doberman Pinschers in which results of echocardiography were abnormal. DESIGN: Clinical case series. ANIMALS: 56 (35 male, 21 female) overtly healthy Doberman Pinschers with echocardiographic evidence of cardiomyopathy on initial examination that subsequently died of cardiomyopathy. PROCEDURE: Twenty-four-hour ambulatory electrocardiographic (Holter) recordings obtained at the time of initial examination were reviewed. For all dogs, scan quality was > 90%. RESULTS: Initial Holter recordings of all 56 dogs contained ventricular premature contractions (VPC). Thirty-six (65%) dogs had > 1,000 VPC/24 h, 17 (31%) had > 5,000 VPC/24 h, and 11 (19%) had > 10,000 VPC/24 h. Fifty-four (96%) dogs had couplets of VPC, 37 (66%) had triplets of VPC, and 36 (64%) had episodes of nonsustained (< 30 seconds) ventricular tachycardia. Number of VPC/24 h during the initial Holter recordings was positively correlated with numbers of couplets and triplets of VPC and number of ventricular escape beats and negatively correlated with left ventricular fractional shortening. Twenty-eight dogs died suddenly prior to the putative onset of congestive heart failure. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that along with echocardiography, 24-hour ambulatory electrocardiography can be used to help identify overtly healthy Doberman Pinschers with cardiomyopathy.     

Correlation of motor evoked potentials with magnetic resonance imaging and neurologic findings in Doberman Pinschers with and without signs of cervical spondylomyelopathy

OBJECTIVE: To establish the reference ranges for motor evoked potential (MEP) latency and amplitude in clinically normal Doberman Pinschers, compare the MEPs of Doberman Pinschers with and without clinical signs of cervical spondylomyelopathy (CSM; wobbler syndrome), and determine whether MEP data correlate with neurologic or magnetic resonance imaging (MRI) findings. ANIMALS: 16 clinically normal and 16 CSM-affected Doberman Pinschers. PROCEDURES: Dogs were classified according to their neurologic deficits. After sedation with acepromazine and hydromorphone, transcranial magnetic MEPs were assessed in each dog; latencies and amplitudes were recorded from the extensor carpi radialis and cranial tibial muscles. Magnetic resonance imaging was performed to evaluate the presence and severity of spinal cord compression. RESULTS: Significant differences in cranial tibial muscle MEP latencies and amplitudes were detected between clinically normal and CSM-affected dogs. No differences in the extensor carpi radialis MEP were detected between groups. There was a significant correlation (r = 0.776) between the cranial tibial muscle MEP latencies and neurologic findings. Significant correlations were also found between MRI findings and the cranial tibial muscle MEP latencies (r = 0.757) and amplitudes (r = -0.453). CONCLUSIONS AND CLINICAL RELEVANCE: Results provided a reference range for MEPs in clinically normal Doberman Pinschers and indicated that cranial tibial muscle MEP latencies correlated well with both MRI and neurologic findings. Because of the high correlation between cranial tibial muscle MEP data and neurologic and MRI findings, MEP assessment could be considered as a screening tool in the management of dogs with spinal cord disease.     

Resting and Dobutamine Stress Echocardiographic Factors Associated with the Development of Occult Dilated Cardiomyopathy in Healthy Doberman Pinscher Dogs

In 29 healthy Doberman Pinschers, echocardiographic parameters evaluating systolic and diastolic function were examined prospectively at rest and during dobutamine constant rate infusion (5 μg/kg/minute) to determine if any parameters were associated with the development of occult dilated cardiomyopathy (DCM). A resting echocardiogram was repeated 1 year later to determine which dogs had met our criteria for occult DCM. Six dogs developed occult DCM during the follow-up period. Univariate logistic regression analysis showed that at rest, an increased left ventricular internal dimension in systole (LVID-S) ( P = .02), preejection period (PEP) ( P = .03), ratio of PEP to left ventricular ejection time ( P = .02), and isovolumic relaxation time ( P = .02) were significantly associated with the development of occult DCM. During dobutamine stress echocardiography (DSE), high LVID-S ( P = .02) and systolic wall stress index ( P = .04) and reduced fractional shortening ( P = .02) and ratio of peak early to late diastolic mitral filling velocity (E/A) ( P = .05) were associated with the development of occult DCM. Multiple logistic regression showed that LVID-S ( P = .002) and E/A ( P = .002) measured during dobutamine infusion also were associated with the development of occult DCM. Reclassification based on the DSE data was not significantly different than reclassification based on the resting echocardiographic data. Resting echocardiography and DSE have the potential to be clinically applicable screening tests for very early systolic and diastolic dysfunction in Doberman Pinschers, heralding the onset of occult DCM as it is currently defined.     

Plasma fatty acid concentrations in Boxers and Doberman Pinschers

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 gamma-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.     

Correlation of mitochondrial protein expression in complexes I to V with natural and induced forms of canine idiopathic dilated cardiomyopathy

OBJECTIVE: To identify qualitative and quantitative differences in cardiac mitochondrial protein expression in complexes I to V between healthy dogs and dogs with natural or induced dilated cardiomyopathy (DCM). SAMPLE POPULATION: Left ventricle samples were obtained from 7 healthy dogs, 7 Doberman Pinschers with naturally occurring DCM, and 7 dogs with DCM induced by rapid right ventricular pacing. PROCEDURES: Fresh and frozen mitochondrial fractions were isolated from the left ventricular free wall and analyzed by 2-dimensional electrophoresis. Protein spots that increased or decreased in density by 2-fold or greater between groups were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or quadrupole selecting, quadrupole collision cell, time-of-flight mass spectrometry. RESULTS: A total of 22 altered mitochondrial proteins were identified in complexes I to V. Ten and 12 were found in complex I and complexes II to V, respectively. Five were mitochondrial encoded, and 17 were nuclear encoded. Most altered mitochondrial proteins in tissue specimens from dogs with naturally occurring DCM were associated with complexes I and V, whereas in tissue specimens from dogs subjected to rapid ventricular pacing, complexes I and IV were more affected. In the experimentally induced form of DCM, only nuclear-encoded subunits were changed in complex I. In both disease groups, the 22-kd subunit was downregulated. CONCLUSIONS AND CLINICAL RELEVANCE: Natural and induced forms of DCM resulted in altered mitochondrial protein expression in complexes I to V. However, subcellular differences between the experimental and naturally occurring forms of DCM may exist.     

Results of ambulatory electrocardiography in overtly healthy Doberman Pinschers with equivocal echocardiographic evidence of dilated cardiomyopathy

OBJECTIVE: To determine results of ambulatory electrocardiography in and outcome of overtly healthy Doberman Pinschers with equivocal echocardiographic evidence of dilated cardiomyopathy. DESIGN: Case series. ANIMALS: 44 overtly healthy (25 male, 19 female) Doberman Pinschers. PROCEDURE: 24-hour ambulatory electrocardiographic (Holter) recordings with > 90% scan quality obtained the same day that echocardiography was performed were reviewed. RESULTS: Holter recordings from 42 of 44 (95%) dogs contained ventricular premature complexes (VPC). Fifteen of 44 (34%) dogs had > 100 VPC, 9 (20%) had > 500 VPC, and 5 (11%) had > 1,000 VPC. Nonsustained (< 30 seconds) ventricular tachycardia was detected in 4 dogs. Eighteen of 27 (67%) dogs with > 100 VPC, any couplets or triplets of VPC, or ventricular tachycardia developed dilated cardiomyopathy within 1 year, compared with 8 of 17 (47%) dogs with < 100 VPC, no couplets or triplets of VPC, and no ventricular tachycardia. Of the 18 dogs that did not develop dilated cardiomyopathy within 1 year, 11 (61%) did so within 3 years. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that a high percentage of Doberman Pinschers with equivocal echocardiographic evidence of dilated cardiomyopathy will be found to have VPC during 24-hour ambulatory electrocardiography and that most will develop echocardiographic abnormalities indicative of cardiomyopathy.