Plasma Taurine Concentrations in Normal Dogs and in Dogs With Heart Disease

Plasma taurine concentrations were determined in 76 dogs with dilated cardiomyopathy (DCM), 28 dogs with acquired valvular disease (AVD), and 47 normal (control) dogs. The data were collected at 2 referral centers. The Animal Medical Center, New York, NY (AMC), and the University of California, Davis (UCD), and the studies were conducted independently. Different anticoagulants (sodium citrate at AMC and lithium heparin at UCD) were used to collect the plasma samples. Paired analysis of samples showed a significant difference in plasma taurine concentrations, depending on the anticoagulant used. Consequently, results from each clinic were analyzed separately. Plasma taurine concentrations were significantly higher in dogs with AVD (median, 133 nmol/mL; range, 25 to 229 nmol/mL) than in control dogs (median, 63 nmol/mL; range 44 to 224 nmol/mL) and dogs with DCM (median, 72 nmol/mL; range, 1 to 247 nmol/mL) at AMC (P= .001). The number of dogs with AVD at UCD was too small to draw meaningful conclusions. At UCD, the median plasma taurine concentration was 98 nmol/mL (range, 28–169 nmol/mL) in dogs with AVD, 75 nmol/mL (range, 0.1–184 nmol/mL) in dogs with DCM, and 88 nmol/mL (range 52–180 nmol/mL) in control dogs. There were no significant differences in plasma taurine concentrations between dogs with DCM and the control dogs at either hospital. Congestive heart failure and administration of cardiac medication had no significant effect on plasma taurine concentrations. Plasma taurine concentration was low (<25 nmol/mL) in 17% (13/76) of the dogs with DCM. Seven of the 13 dogs with low plasma taurine concentrations were Cocker Spaniels or Golden Retrievers. It was concluded that most dogs with DCM do not have low plasma taurine concentrations. However, certain breeds or individual dogs may have low plasma taurine concentrations in association with DCM. Whether this association is causal or not is unknown. The significance of the high plasma taurine concentrations in dogs with AVD is also unknown.     

Vasopressin, cortisol, and catecholamine concentrations in dogs with dilated cardiomyopathy

OBJECTIVE: To evaluate plasma concentrations and urinary excretion of vasopressin and cortisol and urinary excretion of catecholamines in dogs with dilated cardiomyopathy (DCM). ANIMALS: 15 dogs with clinical signs of DCM, 15 dogs with preclinical DCM, and 15 control dogs. PROCEDURE: Physical examinations, thoracic radiography, ECG, and echocardiography were performed on all dogs. Blood and urine samples were collected. RESULTS: Plasma concentration of vasopressin and the urine cortisol-to-urine creatinine ratio were significantly increased in dogs with clinical signs of DCM and dogs with preclinical DCM, compared with control dogs. Plasma vasopressin concentration was significantly higher in dogs with clinical signs of DCM, compared with dogs with preclinical DCM. Urine vasopressin-to-urine creatinine ratio was significantly increased in dogs with clinical signs of DCM, compared with dogs with preclinical DCM and control dogs. Urine epinephrine-to-urine creatinine ratio and urine norepinephrine-to-urine creatinine ratio were significantly increased in dogs with clinical signs of DCM, compared with control dogs. Plasma concentration of cortisol and urine dopamine-to-urine creatinine ratio did not differ significantly among groups. CONCLUSIONS AND CLINICAL RELEVANCE: According to this study, the neuroendocrine pattern is changed in dogs with preclinical DCM. These changes are even more pronounced in dogs with clinical signs of DCM. Analysis of concentrations of vasopressin, cortisol, and catecholamines may aid in identification of the clinical stages of DCM. These findings may also provide a basis for additional studies of the possible beneficial effects of vasopressin antagonists and beta-adrenergic receptor antagonists in the treatment of dogs with congestive heart failure and DCM.     

Polymerase chain reaction analysis for viruses in paraffin-embedded myocardium from dogs with dilated cardiomyopathy or myocarditis

OBJECTIVE: To perform polymerase chain reaction (PCR) analysis on paraffin-embedded myocardium from dogs with dilated cardiomyopathy (DCM) and dogs with myocarditis to screen for canine parvovirus, adenovirus types 1 and 2, and herpesvirus. SAMPLE POPULATION: Myocardial specimens from 18 dogs with an antemortem diagnosis of DCM and 9 dogs with a histopathologic diagnosis of myocarditis were evaluated. PROCEDURE: Paraffin-embedded myocardial specimens were screened for viral genome by PCR analysis. Positive-control specimens were developed from cell cultures as well as paraffin-embedded tissue specimens from dogs with clinical and histopathologic diagnoses of viral infection with canine parvovirus, adenovirus types 1 and 2, and herpesvirus. The histologic characteristics of all myocardial specimens were classified regarding extent, location, and type of inflammation and fibrosis. RESULTS: Canine adenovirus type 1 was amplified from 1 specimen from a dog with DCM. Canine parvovirus, adenovirus type 2, and herpesvirus were not amplified from any myocardial specimens. Histologic analysis of specimens from dogs with DCM revealed variable amounts of fibrosis; myocardial inflammation was observed in 1 affected dog. Histopathologic analysis of specimens from dogs with myocarditis disclosed variable degrees of inflammation and fibrosis. CONCLUSIONS AND CLINICAL RELEVANCE: Viral agents canine parvovirus, adenovirus types 1 and 2, and herpesvirus are not commonly associated with DCM or active myocarditis in dogs. Additional studies evaluating for nucleic acid from viruses that less commonly affect dogs or different types of infectious agents may be warranted to gain insight into the cause of DCM and myocarditis in dogs.     

The potential role of myocardial serotonin receptor 2B expression in canine dilated cardiomyopathy

Serotonin signalling in the heart is mediated by receptor subtype 2B (5-HTR2B). A contribution of serotonin to valvular disease has been reported, but myocardial expression of 5-HTR2B and its role in canine dilated cardiomyopathy (DCM) is not known. The aim of the present study was to investigate myocardial 5-HTR2B mRNA expression in dogs with DCM and to correlate results with expression of markers for inflammation and remodelling. Myocardial samples from eight healthy dogs, four dogs with DCM, five with cardiac diseases other than DCM and six with systemic non-cardiac diseases were investigated for 5-HTR2B mRNA expression using quantitative PCR (qPCR). The results were compared to mRNA expression of selected cytokines, matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinase (TIMP). Laser microdissection with subsequent qPCR and immunohistochemistry were employed to identify the cells expressing 5-HTR2B.The myocardium of control dogs showed constitutive 5-HTR2B mRNA expression. In dogs with DCM, 5-HTR2B mRNA values were significantly greater than in all other groups, with highest levels of expression in the left ventricle and right atrium. Myocytes were identified as the source of 5-HTR2B mRNA and protein. A significant positive correlation of 5-HTR2B mRNA with expression of several cytokines, MMPs and TIMPs was observed. The findings suggest that serotonin might play a role in normal cardiac structure and function and could contribute to myocardial remodelling and functional impairment in dogs with DCM.     

Characterization of canine mitochondrial protein expression in natural and induced forms of idiopathic dilated cardiomyopathy

OBJECTIVE: To map canine mitochondrial proteins and identify qualitative and quantitative differences in heart mitochondrial protein expression between healthy dogs and dogs with naturally occurring and 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 induced DCM. 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 >or= 2-fold 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: Within narrow pH gradients of control canine heart mitochondrial samples, a total of 1,528 protein spots were revealed. Forty subunits of heart mitochondrial proteins that differ significantly from control tissues were altered in tissue specimens from dogs with naturally occurring and induced forms of DCM. The most affected heart mitochondrial proteins in both groups were those of oxidative phosphorylation (55%). Upregulation of manganese superoxide dismutase was suggestive of heart oxidative injury in tissue specimens from dogs with both forms of DCM. Evidence of apoptosis was associated with overexpression of the heart mitochondrial voltage-dependent anion channel-2 protein and endonuclease G in tissue specimens from dogs with induced DCM. CONCLUSIONS AND CLINICAL RELEVANCE: Alterations of heart mitochondrial proteins related to oxidative phosphorylation dysfunction were more prevalent in tissue specimens from dogs with induced or naturally occurring DCM, compared with those of control dogs.     

Effects of dilated cardiomyopathy on the renin-angiotensin-aldosterone system, atrial natriuretic peptide activity, and thyroid hormone concentrations in dogs

OBJECTIVE: To evaluate the effect of dilated cardiomyopathy (DCM) on activity of the renin-angiotensin-aldosterone system (RAAS), the N-terminal fragment of proatrial natriuretic peptide (NT-proANP), and thyroid hormone concentrations in dogs. ANIMALS: 15 dogs with clinical signs of DCM, 15 dogs without clinical signs of DCM, and 15 age-, breed-, and sex-matched control dogs. PROCEDURE: Physical examinations, thoracic radiography, ECG, and echocardiography were performed on all dogs, and blood and urine samples were collected. RESULTS: Plasma renin activity (PRA), plasma aldosterone concentration (PAC), urine aldosterone-to-creatinine ratio, and NT-proANP concentrations were significantly increased in dogs with clinical signs of DCM, compared with dogs without clinical signs and control dogs. Thyroid-stimulating hormone and total thyroxine concentrations did not differ significantly among groups; however, free thyroxine (FT4) concentrations were significantly decreased in dogs with clinical signs of DCM, compared with control dogs and DCM-dogs without clinical signs. Concentrations of PRA, PAC, FT4, and urine aldosterone-to-creatinine ratio were significantly correlated, whereas plasma concentrations of NT-proANP only correlated with FT4 concentration. CONCLUSION AND CLINICAL RELEVANCE: In dogs with clinical signs of DCM, increased concentrations of components of the RAAS were associated with increased concentrations of NT-proANP Analysis of the neurohormonal system may aid in identification of clinical stages of DCM for groups of dogs, but the range is too great and there are too many dogs that have neurohormonal concentrations within reference ranges to assess dogs on an individual basis.     

Serum cardiac troponin I and cardiac troponin T concentrations in dogs with gastric dilatation-volvulus

OBJECTIVE: To determine whether serum concentrations of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) are increased in dogs with gastric dilatationvolvulus (GDV) and whether concentrations correlate with severity of ECG abnormalities or outcome. DESIGN: Prospective case series. ANIMALS: 85 dogs with GDV. PROCEDURE: Serum cTnl and cTnT concentrations were measured 12 to 24, 48, 72, and 96 hours after surgery. Dogs were grouped on the basis of severity of ECG abnormalities and outcome. RESULTS: cTnl and cTnT were detected in serum from 74 (87%) and 43 (51%) dogs, respectively. Concentrations were significantly different among groups when dogs were grouped on the basis of severity of ECG abnormalities (none or mild vs moderate vs severe). Dogs that died (n = 16) had significantly higher serum cTnI (24.9 ng/ml) and cTnT (0.18 ng/ml) concentrations than did dogs that survived (2.05 and < 0.01 ng/ml, respectively). Myocardial cell injury was confirmed at necropsy in 4 dogs with high serum cardiac troponin concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that concentrations of cTnI and cTnT suggestive of myocardial cell injury can commonly be found in serum from dogs with GDV and that serum cardiac troponin concentrations are associated with severity of ECG abnormalities and outcome.     

Serum nitrate and nitrite in dogs with spontaneous cardiac disease

The purpose of this study was to determine whether nitric oxide (NO) concentrations are high in dogs with chronic valvular disease (CVD) and dilated cardiomyopathy (DCM) compared to healthy controls and to determine whether NO concentrations are correlated with type of cardiac disease, disease severity, medical therapy, or serum tumor necrosis factor (TNF) and interleukin-1 (IL-1). Blood was collected from 32 dogs with DCM, from 10 dogs with CVD, and from 10 healthy controls. Indirect determination of NO concentrations was performed by a commercial photoabsorbance assay that uses a Greiss reagent to measure the concentration of nitrite and nitrate (NN), end products of NO metabolism. TNF and IL-1 activities were measured by bioassay. Mean NN concentrations were significantly higher in dogs with heart disease (median, 4.57 microM; range, 0.00-31.05 microM) than in controls (median, 0.00 microM; range, 0.00-6.16 microM; P = .04). NN concentrations in dogs with cardiac disease were not correlated with type or severity of cardiac disease, medication type, or TNF and IL-1 concentrations. NN concentrations were inversely correlated with fractional shortening. The results of this study suggest that metabolites of NO are increased in some dogs with cardiac disease, but these increases appear to be independent of disease severity, TNF and IL-1 concentrations, and type of pharmacologic intervention.     

Correlation between activation of the sympathetic nervous system estimated by plasma concentrations of norepinephrine and Doppler echocardiographic variables in dogs with acquired heart disease

OBJECTIVE: To evaluate correlations between plasma concentrations of norepinephrine and Doppler echocardiographic variables for dogs with degenerative mitral valve disease (DMVD) or dilatative cardiomyopathy (DCM) to better understand the time course and magnitude of sympathetic activation in dogs with heart failure (HF). ANIMALS: 15 healthy dogs, 15 dogs with DMVD, and 15 dogs with DCM. PROCEDURES: Dogs were positioned in lateral recumbency with minimal restraint for at least 20 minutes. Plasma samples were obtained and assayed by use of high-performance liquid chromatography. Concentrations were correlated with HF classification and with the main Doppler echocardiographic variables for each group. RESULTS: Mean +/- SD norepinephrine concentration was significantly higher in dogs with DMVD (494.4 +/- 204.8 pg/mL) or DCM (655.7 +/- 652.5 pg/mL) than in healthy dogs (205.8 +/- 78.9 pg/mL), but concentrations did not differ significantly between the 2 groups with HF. Correlations were not detected between norepinephrine and heart rate or any M-mode echocardiographic variables evaluated, except for fractional shortening (FS) in DCM dogs. In that group, norepinephrine was inversely correlated with FS values. In DMVD dogs, no significant correlation was found between norepinephrine and the left atrium-to-aortic root ratio or mitral regurgitation. CONCLUSIONS AND CLINICAL RELEVANCE: A proportional inverse correlation exists between norepinephrine and FS values in dogs with DCM. However, norepinephrine concentration was not correlated with the evaluated echocardiographic variables in dogs with DMVD. Sympathetic antagonists should be evaluated as a treatment option because of the increased plasma concentrations of norepinephrine detected in dogs with HF.     

Sympathetic activation in dogs with congestive heart failure caused by chronic mitral valve disease and dilated cardiomyopathy

Baseline plasma norepinephrine (NE) and epinephrine (EPI) concentrations were measured in dogs with naturally acquired heart failure (HF) caused by either degenerative mitral valve disease and mitral regurgitation (MR) or idiopathic dilated cardiomyopathy (DCM). Compared with controls (clinically normal), dogs with HF had increased plasma NE concentration, which was correlated positively with clinical severity of HF. Dogs with the most severe degree of HF (New York Heart Association functional class IV) had mean NE concentration significantly (P less than 0.05) greater than that of dogs with all other functional classes of HF. Overall, mean NE concentration in dogs with DCM was greater than that in dogs with MR. Plasma EPI concentration was not different between control dogs and dogs with HF or between dogs with DCM or MR. Correlations were not found between the echocardiographically derived end systolic volume index (used as an estimate of myocardial function) and plasma NE and EPI concentrations or serum sodium or potassium concentration. Dogs with DCM, as a group, had a small but significant (P less than 0.05) decrease in serum sodium concentration, compared with dogs with MR. This difference was maintained only for class-IV HF when dogs were separated according to functional HF class. In dogs with DCM, significant inverse correlation was found between plasma NE and serum sodium concentrations. When grouped together, all dogs with HF maintained this relationship; however, dogs with MR did not have correlation between plasma NE and serum sodium concentrations. Plasma EPI and serum sodium concentrations were not correlated for any group. It was concluded that in dogs, plasma NE, but not EPI, concentration is high in relation to the clinical severity of naturally acquired HF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of western immunoblot for evaluation of myocardial dystrophin, alpha-sarcoglycan, and beta-dystroglycan in dogs with idiopathic dilated cardiomyopathy

OBJECTIVE: To evaluate the potential importance of dystrophin, alpha-sarcoglycan (adhalin), and beta-dystroglycan, by use of western blot analysis, in several breeds of dogs with dilated cardiomyopathy. SAMPLE POPULATION: Myocardial samples obtained from 12 dogs were evaluated, including tissues from 7 dogs affected with dilated cardiomyopathy, 4 control dogs with no identifiable heart disease (positive control), and 1 dog affected with Duchenne muscular dystrophy (negative control for dystrophin). Of the affected dogs, 4 breeds were represented (Doberman Pinscher, Dalmatian, Bullmastiff, and Irish Wolfhound). PROCEDURE: Western blot analysis was used for evaluation of myocardial samples obtained from dogs with and without dilated cardiomyopathy for the presence of dystrophin and 2 of its associated glycoproteins, alpha-sarcoglycan and beta-dystroglycan. RESULTS: Detectable differences were not identified between dogs with and without myocardial disease in any of the proteins evaluated. CONCLUSIONS AND CLINICAL RELEVANCE: Abnormalities in dystrophin, alpha-sarcoglycan, and beta-dystroglycan proteins were not associated with the development of dilated cardiomyopathy in the dogs evaluated in this study. In humans, the development of molecular biological techniques has allowed for the identification of specific causes of dilated cardiomyopathy that were once considered to be idiopathic. The use of similar techniques in veterinary medicine may aid in the identification of the cause of idiopathic dilated cardiomyopathy in dogs, and may offer new avenues for therapeutic intervention.     

Effects of dietary n-6 and n-3 fatty acids and vitamin E on the immune response of healthy geriatric dogs

OBJECTIVE: To determine the effect of dietary n-6 to n-3 fatty acid ratios and alpha-tocopheryl acetate concentration on immune functions andT cell subpopulations in healthy dogs. ANIMALS: Thirty-two 7- to 10-year old female Beagles. PROCEDURE: For 17 weeks, dogs were fed food that contained low (1.4:1) or high (40:1) ratios of n-6 to n-3 fatty acids in combination with 3 concentrations of all rac-alpha-tocopheryl acetate (low, 17 mg/kg of food; medium, 101 mg/kg; high, 447 mg/kg). Dogs were inoculated twice with a keyhole limpet hemocyanin suspension at 13 and 15 weeks. RESULTS: After 12 weeks, dogs consuming low concentrations of alpha-tocopheryl acetate had lower percentages of CD8+ T cells, compared with dogs consuming medium or high alpha-tocopheryl acetate concentrations. Also, dogs consuming low alpha-tocopheryl acetate concentrations had higher CD4+ to CD8+ T cell ratios. On day 4 of week 15, the percentage of CD8+ T cells was highest in dogs fed medium concentrations of alpha-tocopheryl acetate, compared with other dogs; however, the CD4+ to CD8+ T cell ratio was higher only in dogs fed low concentrations of alpha-tocopheryl acetate with high concentrations of n-3 fatty acids. Dogs consuming low concentrations of n-3 fatty acids with medium concentrations of alpha-tocopheryl acetate had the largest delayed-type hypersensitivity (DTH) skin test response. CONCLUSIONS AND CLINICAL RELEVANCE: An optimum amount of dietary alpha-tocopheryl acetate concentration, regardless of the dietary n-6 to n-3 fatty acid ratio, stimulates the CD8+ T cell population. Effects of an optimum amount of dietary alpha-tocopheryl acetate concentration on the DTH response are blunted by dietary n-3 fatty acids.     

Serum cardiac troponin I concentration in dogs with ehrlichiosis

Background: Ehrlichiosis is a multisystemic disease with the potential to cause cardiomyocyte injury in naturally infected dogs.
Hypothesis: Myocardial injury occurs in dogs infected with Ehrlichia canis .
Animals: One-hundred and ninety-four dogs from Brazil with clinical and laboratory abnormalities indicative of ehrlichiosis. Sixteen healthy dogs served as controls.
Methods: Electrocardiogram, echocardiogram, noninvasive blood pressure measurement, and serum cardiac troponin I (cTnI) concentrations were evaluated. Serologic assays and PCR determined the exposure and infection status for E. canis, Anaplasma spp., Babesia canis vogeli, Bartonella spp., Borrelia burgdorferi, Dirofilaria immitis, Ehrlichia chaffeensis, Ehrlichia ewingii, Leishmania chagasi , and spotted-fever group Rickettsia . Dogs were assigned to groups according to PCR status: E. canis infected, infected with other vector-borne organisms, sick dogs lacking PCR evidence for infection, and healthy controls.
Results: E. canis -infected dogs had higher serum cTnI concentrations than controls (median: 0.04 ng/dL; range 0.04–9.12 ng/dL; control median: 0.04 ng/dL; range: 0.04–0.10 ng/dL; P = .012), and acute E. canis infection was associated with myocardial injury (odds ratio [OR]: 2.67, confidence interval [CI] 95%: 1.12–6.40, P = .027). Severity of anemia was correlated with increased risk of cardiomyocyte damage ( r = 0.84, P < .001). Dogs with clinical signs of systemic inflammatory response syndrome (SIRS) were at higher risk for myocardial injury than were other sick dogs (OR: 2.55, CI 95%: 1.31–4.95, P = .005).
Conclusions and Clinical Importance: Acute infection with E. canis is a risk factor for myocardial injury in naturally infected Brazilian dogs. Severity of anemia and SIRS might contribute to the pathophysiology of myocardial damage.     

Influence of dietary long-chain n-3 fatty acids from menhaden fish oil on plasma concentrations of alpha-tocopherol in geriatric beagles

OBJECTIVE: To determine effects of dietary n-3 fatty acids from Menhaden fish oil on plasma alpha-tocopherol concentrations in Beagles. ANIMALS: 32 female Beagles. PROCEDURE: For 82 days, dogs were fed diets that contained 1 of 2 ratios of n-6:n-3 fatty acids (40:1 [low n-3] and 1.4:1 [high n-3]) and 1 of 3 concentrations of all-rac-alpha-tocopheryl acetate (low, 17 mg/kg of diet; medium, 101 mg/kg; and high, 447 mg/kg) in a 2 X 3 factorial study. RESULTS: Diets high in n-3 fatty acids significantly increased total content of n-3 fatty acids in plasma (17.0 g/100 g of fatty acids), compared with low n-3 diets (2.02 g/100 g of fatty acids). Mean +/- SEM plasma concentration of cholesterol was significantly lower in dogs consuming high n-3 diets (4.59 +/- 0.48 mmol/L), compared with dogs consuming low n-3 diets (5.71 +/- 0.48 mmol/L). A significant interaction existed between the ratio for n-6 and n-3 fatty acids and amount of alpha-tocopheryl acetate in the diet (plasma alpha-tocopherol concentration expressed on a molar basis), because the plasma concentration of alpha-toco-pherol was higher in dogs consuming low n-3 diets, compared with those consuming high n-3 diets, at the 2 higher amounts of dietary alpha-tocopheryl acetate. Plasma alpha-tocopherol concentration expressed relative to total lipid content did not reveal effects of dietary n-3 fatty acids on concentration of alpha-tocopherol. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma alpha-tocopherol concentration is not dependent on dietary ratio of n-6 and n-3 fatty acids when alpha-tocopherol concentration is expressed relative to the total lipid content of plasma.     

Plasma big endothelin-1, atrial natriuretic peptide, aldosterone, and norepinephrine concentrations in normal Doberman Pinschers and Doberman Pinschers with dilated cardiomyopathy

BACKGROUND: Dilated cardiomyopathy (DCM) results in progressive myocardial and circulatory dysfunction causing activation of a number of neurohormonal systems, including the endothelin (ET) system, which is only beginning to be described in clinical veterinary medicine. Measurement of these circulating neurohormones possesses potential utility in the diagnosis, staging, and assessment of prognosis in cardiac disease. HYPOTHESIS: We hypothesized that plasma big ET-1, norepinephrine (NE), aldosterone, and atrial natriuretic peptide (ANP) concentrations in normal Dobermans would differ from those in Dobermans with DCM, and that concentrations of these hormones would be associated with time to congestive heart failure (CHF) or death. ANIMALS: Thirty client-owned Dobermans (10 each of normal, occult DCM, and overt DCM) were included in the study. METHODS: Dogs underwent an echocardiogram, ECG, and blood sample collection. Neurohormones were measured by high-pressure liquid chromatography (NE) or commercial assays. RESULTS: Dogs with occult DCM had significantly higher ANP concentrations compared with normal dogs (least squares means [95% confidence interval, CI]: occult female 53.7 pg/mL [40.2-71.7] versus normal female 31.6 pg/mL [24.8-40.3], P = .026; occult male 86.1 pg/mL [64.7-115] versus normal male 12.1 pg/mL [5.1-28.7], P = .011). Dogs with overt DCM had significantly higher concentrations of all neurohormones compared with the normal group. Furthermore, increasing big ET-1 (risk ratio [RR] 2.7, CI 1.3-8.6, P = .01) and NE concentrations (RR 3.9, CI 1.1-18.1, P = .03) over 1 month were associated with a shorter survival time. CONCLUSIONS AND CLINICAL IMPORTANCE: High ANP concentrations can identify dogs with advanced occult DCM. Increasing big ET-1 or NE concentrations over time can be useful predictors of poor prognosis.     

Prospective screening for occult cardiomyopathy in dogs by measurement of plasma atrial natriuretic peptide, B-type natriuretic peptide, and cardiac troponin-I concentrations

OBJECTIVE: To evaluate the use of measuring plasma concentrations of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and cardiac troponin-I (cTnI) to detect dogs with occult dilated cardiomyopathy (DCM). ANIMALS: 118 client-owned dogs. PROCEDURES: Dogs were prospectively examined by use of ECG; echocardiography; and evaluation of concentrations of ANP, BNP, and cTnI. Occult DCM was diagnosed by evaluation of echocardiographic left ventricular dimensions and detection of ventricular arrhythmias on ECG. Sensitivity and specificity of assays for measurement of plasma concentrations of ANP, BNP, and cTnI to detect dogs with occult DCM were determined. RESULTS: Occult DCM was diagnosed in 21 dogs. A concentration of > 6.21 pg/mL for BNP had a sensitivity of 95.2% and specificity of 61.9% for identifying dogs with occult DCM. In contrast, concentrations of ANP and cTnI had relatively low predictive values. CONCLUSIONS AND CLINICAL RELEVANCE: Blood-based screening for occult DCM in dogs can be accomplished by use of a BNP assay. Additional studies should be performed to optimize this method of screening dogs to detect occult DCM.     

Lymphocyte beta -adrenoceptor downregulation in great danes with occult dilated cardiomyopathy (DCM) and with DCM and heart failure.

The importance of the adrenergic nervous system in supporting the failing heart has long been known. The adrenergic drive on cardiac structure and function has however some adverse effects, which include myocardial beta-adrenoceptor (beta-AR) downregulation and decreased beta-adrenergic responsiveness to cathecolamines. In dog lymphocytes, beta(1)-AR and beta(2)-AR populations are almost equally represented (with a slight prevalence of beta(2)) and a significant correlation between cardiac and lymphocytic adrenoceptors has been found. The aim of the present study was to investigate possible differences between the concentration of lymphocytic beta-AR in healthy dogs, dogs with dilated cardiomyopathy (DCM) and dogs with occult DCM. Three groups of great danes were considered: a control group (n =10), dogs with DCM (n =9) and dogs with occult DCM (n =4). Lymphocytic beta-AR populations were determined in all dogs. A substantial and significant decrease (P<0.05) in total-AR, beta(1)-AR and beta(2)-AR concentrations in the lymphocytes of dogs with symptomatic DCM and occult DCM compared to the control group was found. Although the mean value of the lymphocyte beta(1)-AR number in the asymptomatic group was double compared to the DCM group, this difference was not statistically significant. We conclude that in dogs beta-AR downregulation occurs early in the course of dilated cardiomyopathy. This finding may suggest the value of early use of a beta-blocker in the therapeutic regimen. Moreover, the continuous monitoring of lymphocytic beta-AR may represent a useful tool for the development of a more effective individual therapy.     

Canine dilated cardiomyopathy: lymphocyte and cardiac alpha(1)- and beta-adrenoceptor concentrations in normal and affected great danes.

Serum catecholamine levels and myocardial and lymphocyte adrenergic receptor (AR) concentrations were measured in adult great danes affected by canine dilated cardiomyopathy (DCM) and compared to those of healthy animals. A non-homogeneous population of beta -AR, consisting of beta(1)-AR and beta(2)-AR, was observed in healthy (41 and 59%, respectively) and affected (17 and 83%, respectively) dog lymphocytes. Binding assays revealed that total beta -AR, beta(1)-AR and alpha(1)-AR were significantly downregulated (P<0.05;P<0.01;P<0. 001), both in lymphocyte and myocardial cell membranes of affected dogs. beta(2)-Adrenergic receptor concentrations were significantly reduced only in lymphocyte and right atrium cell membranes (P<0.05). Downregulation was not associated with alterations in receptor binding characteristics, as no significant differences in K(d)values were found. Mean plasma catecholamine levels were significantly higher (P<0.01) in DCM dogs (939+/-41) than in normal subjects (348+/-32), thus suggesting a sympathetic activation. The present study indicates a condition similar to that observed in human patients affected by DCM and that adrenergic receptors in canine lymphocytes reflect the fluctuation of adrenergic receptor concentrations in the myocardium.