RESUMO
Qualitative assessment of individual cardiac chamber enlargement on thoracic radiographs was assessed using echocardiography as the gold standard in dogs. Using this method, the presence of severe left-sided cardiomegaly was hypothesized to contribute to the false identification of right-sided cardiomegaly on radiographs. 175 dogs with three-view thoracic radiographs were retrospectively included in this diagnostic accuracy study if echocardiography was done within 24 h, and no rescue therapy was provided in the interim. All radiographic studies were reviewed by two groups of five board-certified veterinary radiologists with greater and less than 10 years of experience for grading of cardiac chamber enlargement as normal or mildly, moderately, or severely enlarged. The agreement, sensitivity, and specificity of the radiologists' interpretation of cardiac chamber size on thoracic radiographs to measured echocardiographic grades were evaluated. A total of 147 cases had complete echocardiographic data available for analysis. Intragroup agreement was moderate for the evaluation of left atrial enlargement and slight to fair for all other cardiac chambers. Between the mode of the radiologists' responses in the two groups and the echocardiographic grades, there was slight agreement for all cardiac chambers with higher severity grades reported using echocardiography. When moderate to severe left-sided cardiomegaly was identified on echocardiography, the sensitivity, specificity, and accuracy of radiographs were low, identifying dogs with radiographic evidence of right-sided cardiomegaly in the absence of corresponding right-sided cardiomegaly on echocardiography. Therefore, thoracic radiographs should be used with caution for the evaluation of cardiac chamber enlargement, particularly in the presence of severe left-sided cardiomegaly.
Assuntos
Cardiomegalia , Doenças do Cão , Animais , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/veterinária , Doenças do Cão/diagnóstico por imagem , Cães , Ecocardiografia/veterinária , Coração , Radiografia , Estudos RetrospectivosRESUMO
BACKGROUND: Most patients affected with Duchenne muscular dystrophy (DMD) present with arrhythmias and cardiomyopathies. Drugs which potentially may induce tachycardia or hypertension could precipitate acute cardiac failure in these patients and should be avoided. METHODS: Thirty anesthesia records of five experimental male golden retriever cross-bred dogs affected with X-linked muscular dystrophy (GRDM), a model of DMD, were retrospectively reviewed (DMD group). Anesthesia records were compared with those of 10 golden retriever dogs not affected with muscular dystrophy (control group). Records were excluded if dogs received anticholinergics or vasoactive amines. Anesthesia was induced with fentanyl followed by propofol, both intravenously. After orotracheal intubation, all dogs' lungs were mechanically ventilated. Anesthesia was maintained with infusion of fentanyl and propofol (DMD group) or isoflurane in oxygen (control group). Pure O(2) was provided to the DMD group. Cisatracurium (0.1 mg·kg(-1) ) was administered intravenously to all dogs. Five-min interval recordings of HR and systolic blood pressures (SAP) were obtained. RESULTS: Immediately after the administration of cisatracurium, absolute values for HR and SAP significantly increased by 78.3 ± 37.0 b·min(-1) (115.4 ± 64.9%) and 33.0 ± 28.3 mmHg (33.5 ± 31.2%), respectively, in all DMD dogs and remained significantly increased for 10 and 30 min, respectively. Dogs in the control group did not show significant increases in HR or SAP after cisatracurium administration. All dogs recovered from anesthesia without complications. CONCLUSION: In this report, increases in HR and SAP could be associated with the administration of cisatracurium in individuals affected with X-linked muscular dystrophy. These cardiovascular changes deserve further investigation.
Assuntos
Atracúrio/análogos & derivados , Pressão Sanguínea/efeitos dos fármacos , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/fisiopatologia , Fármacos Neuromusculares não Despolarizantes/farmacologia , Anestesia Geral , Anestesia Intravenosa , Anestésicos Intravenosos , Animais , Atracúrio/farmacologia , Dióxido de Carbono/sangue , Cães , Fentanila , Masculino , Propofol , Estudos RetrospectivosRESUMO
Heart rate variability (HRV) is a physiologic phenomenon that occurs due to changing autonomic tone resulting in variable RR intervals. A reduction in HRV is used as an index of pain in neonatal human patients. Objective measures of pain would be valuable in the evaluation of canine patients and assessment of response to pain management strategies. We hypothesized that dogs with diseases associated with discomfort (osteoarthritis and bone neoplasia) would have reduced HRV compared with normal, healthy dogs. The aim of the study was to calculate the sample size necessary to investigate this hypothesis. Seventeen dogs from the Ryan Veterinary Hospital of the University of Pennsylvania patient population or owned by Ryan Veterinary Hospital of the University of Pennsylvania staff were enrolled in this single-blind, prospective pilot study. A 30 min electrocardiogram (ECG) was obtained from each dog using an ambulatory electrocardiographic monitor. All ECGs were obtained between 10 a.m. and 2 p.m. ECGs were analyzed and time-domain HRV indices computed. Sample size calculations suggest that 207 dogs would be necessary to ascertain if HRV is reduced in dogs experiencing discomfort or pain (50 in the arthritis group, 79 in the bone cancer group, and 78 in the control group).
Assuntos
Doenças do Cão , Frequência Cardíaca , Coxeadura Animal , Tamanho da Amostra , Animais , Sistema Nervoso Autônomo , Cães , Eletrocardiografia/veterinária , Projetos PilotoRESUMO
BACKGROUND: Recent interest in cardiac biomarkers has led to the validation of several commercial analyzers for cardiac troponin I (cTnI) evaluation in dogs; however, these analyzers have not been standardized. HYPOTHESIS: It was hypothesized that canine plasma cTnI concentrations as determined by 3 different analyzers would be similar. ANIMALS: Twenty-three dogs with cardiac disease were studied. METHODS: Reconstituted purified canine free cTnI was diluted with canine plasma to 8 concentrations (0.01, 0.1, 0.78, 1.56, 3.13, 6.25, 12.5, and 25 ng/mL), for analysis by 3 analyzers, the Biosite Triage Meter, the Dade-Behring Stratus, and the Beckman-Coulter Access AccuTnI. Plasma samples from 23 dogs with cardiac disease were also analyzed for cTnI concentrations on all analyzers. RESULTS: Troponin I concentrations in sick dogs were <0.05-5.72 ng/mL (Biosite), 0.02-11.1 ng/mL (Access), and 0.02-9.73 ng/mL (Stratus). Analyzer results were highly correlated with each other (r = 0.97 to 1.0 for purified dilutions, r = 0.61 to 0.89 for samples from dogs); however, the limits of agreement were wide for both purified dilutions and clinical samples. Recovery was highest for the Access (334-1467%) and lowest for the Biosite (38-60%); Stratus 52-233%. Analyzer variability was lowest for the Access (1.2-10.4%) and highest for the Stratus (4.8-33.6%); Biosite 2.8-16.5%. CONCLUSIONS AND CLINICAL IMPORTANCE: Results from this study suggest that although canine cTnI values obtained from the Biosite, Stratus, and Access analyzers are closely correlated, they cannot be directly compared with each other. In the absence of a gold standard none of the analyzers can be considered more correct than the others.
Assuntos
Doenças do Cão/sangue , Cardiopatias/sangue , Cardiopatias/veterinária , Imunoensaio/veterinária , Troponina I/sangue , Animais , Biomarcadores/sangue , Doenças do Cão/diagnóstico , Cães , Feminino , Cardiopatias/diagnóstico , Imunoensaio/instrumentação , Modelos Lineares , Masculino , Estatísticas não ParamétricasRESUMO
BACKGROUND: Cardiomyopathy is a leading cause of mortality among Duchenne muscular dystrophy patients and lacks effective therapies. Phosphodiesterase type 5 is implicated in dystrophic pathology, and the phosphodiesterase type 5 inhibitor tadalafil has recently been studied in a clinical trial for Duchenne muscular dystrophy. METHODS AND RESULTS: Tadalafil was evaluated for the prevention of cardiomyopathy in the mdx mouse and golden retriever muscular dystrophy dog models of Duchenne muscular dystrophy. Tadalafil blunted the adrenergic response in mdx hearts during a 30-minute dobutamine challenge, which coincided with cardioprotective signaling, reduced induction of µ-calpain levels, and decreased sarcomeric protein proteolysis. Dogs with golden retriever muscular dystrophy began daily tadalafil treatment prior to detectable cardiomyopathy and demonstrated preserved cardiac function, as assessed by echocardiography and magnetic resonance imaging at ages 18, 21, and 25 months. Tadalafil treatment improved golden retriever muscular dystrophy histopathological features, decreased levels of the cation channel TRPC6, increased total threonine phosphorylation status of TRPC6, decreased m-calpain levels and indicators of calpain target proteolysis, and elevated levels of utrophin. In addition, we showed that Duchenne muscular dystrophy patient myocardium exhibited increased TRPC6, m-calpain, and calpain cleavage products compared with control human myocardium. CONCLUSIONS: Prophylactic use of tadalafil delays the onset of dystrophic cardiomyopathy, which is likely attributed to modulation of TRPC6 levels and permeability and inhibition of protease content and activity. Consequently, phosphodiesterase type 5 inhibition is a candidate therapy for slowing the development of cardiomyopathy in Duchenne muscular dystrophy patients.
Assuntos
Cardiomiopatias/prevenção & controle , Cardiotônicos/uso terapêutico , Distrofina/deficiência , Tadalafila/uso terapêutico , Animais , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/etiologia , Modelos Animais de Doenças , Cães , Ecocardiografia , Humanos , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos mdx , Distrofia Muscular de Duchenne/complicações , Distrofia Muscular de Duchenne/tratamento farmacológico , Canal de Cátion TRPC6/metabolismoRESUMO
Duchenne muscular dystrophy (DMD) is a devastating muscle disease characterized by progressive muscle deterioration and replacement with an aberrant fatty, fibrous matrix. Chronic upregulation of nuclear factor κB (NF-κB) is implicated as a driver of the dystrophic pathogenesis. Herein, 2 members of a novel class of NF-κB inhibitors, edasalonexent (formerly CAT-1004) and CAT-1041, were evaluated in both mdx mouse and golden retriever muscular dystrophy (GRMD) dog models of DMD. These orally bioavailable compounds consist of a polyunsaturated fatty acid conjugated to salicylic acid and potently suppress the pathogenic NF-κB subunit p65/RelA in vitro. In vivo, CAT-1041 effectively improved the phenotype of mdx mice undergoing voluntary wheel running, in terms of activity, muscle mass and function, damage, inflammation, fibrosis, and cardiac pathology. We identified significant increases in dysferlin as a possible contributor to the protective effect of CAT-1041 to sarcolemmal damage. Furthermore, CAT-1041 improved the more severe GRMD phenotype in a canine case study, where muscle mass and diaphragm function were maintained in a treated GRMD dog. These results demonstrate that NF-κB modulation by edasalonexent and CAT-1041 is effective in ameliorating the dystrophic process and these compounds are candidates for new treatments for DMD patients.
RESUMO
PURPOSE: Chronic administration of pharmacological levels of beta2-agonists have been shown to have toxic effects on the heart; however, no data exist on cardiac function after chronic clenbuterol administration. The purpose of this study was to examine the effect of therapeutic levels of clenbuterol on cardiac performance. METHODS: Twenty unfit Standardbred mares were divided into four experimental groups: clenbuterol (2.4 microg.kg(-1) twice daily 5 d.wk(-1)) plus exercise (20 min at 50% .VO(2max)) (CLENEX; N = 6), clenbuterol (CLEN; N = 6), exercise (EX; N = 4), and control (CON; N = 4). M-mode and two-dimensional echocardiography (2.5-MHz sector scanner transducer) were used to measure cardiac size and function before and immediately after an incremental exercise test, before and after 8 wk of drug and/or exercise treatments. RESULTS: After treatment, CLENEX and CLEN demonstrated significantly higher left ventricular internal dimension (LVD) at end diastole (+23.7 +/- 4.8%; +25.6 +/- 4.1%), LVD at end systole (+29.2 +/- 8.7%; +40.1 +/- 7.9%), interventricular septal wall thickness (IVS) at end diastole (+28.9 +/- 11.0%; +30.7 +/- 7.0%), IVS at end systole (+29.2 +/- 8.7%; +40.1 +/- 7.9%), and left ventricular posterior wall systolic thickness (+43.1 +/- 14.%; +45.8 +/- 14.1%). CLENEX and CLEN had significantly increased aortic root dimensions (+29.9 +/- 6.1%; +24.0 +/- 1.7%), suggesting increased risk of aortic rupture. CONCLUSION: Taken together, these data indicate that chronic clenbuterol administration may negatively alter cardiac function.
Assuntos
Agonistas Adrenérgicos beta/efeitos adversos , Clembuterol/efeitos adversos , Coração/efeitos dos fármacos , Coração/fisiopatologia , Remodelação Ventricular , Agonistas Adrenérgicos beta/administração & dosagem , Animais , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Clembuterol/administração & dosagem , Ecocardiografia sob Estresse , Feminino , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Cavalos , Miocárdio/patologia , Condicionamento Físico Animal/fisiologia , Descanso/fisiologiaRESUMO
Dilated cardiomyopathy recently has been recognized in juvenile Portuguese Water Dogs. The purpose of this study was to evaluate unaffected and affected puppies by physical examination, electrocardiogram (ECG), echocardiogram, specific biochemical assays, and ultrastructure to document disease progression and to develop a method of early detection. Results of segregation analysis were consistent with autosomal recessive inheritance. Of 124 puppies evaluated clinically and echocardiographically, 10 were affected. No significant differences were found between unaffected and affected puppies for blood and myocardial carnitine or taurine concentrations, serum chemical variables, results of ophthalmological examinations, ECGs, or measurement of urine metabolites. Ultrastructural examination of myocardium from affected dogs revealed myofibrillar atrophy and small regions of myofibrillar degeneration, most prominently at the region of the intercalated discs. Only echocardiography allowed detection of affected puppies before clinical signs became evident. Echocardiography revealed a significant difference in the shortening fraction, E point to septal separation, and the end systolic and diastolic left ventricular internal diameters. Affected puppies were detected 1-4 weeks before the development of acute congestive heart failure.
Assuntos
Cardiomiopatia Dilatada/veterinária , Doenças do Cão/diagnóstico , Animais , Animais Recém-Nascidos , Cruzamento , Cardiomiopatia Dilatada/diagnóstico , Carnitina/análise , Estudos de Casos e Controles , Progressão da Doença , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/patologia , Cães , Ecocardiografia/veterinária , Eletrocardiografia/veterinária , Miocárdio/ultraestrutura , Exame Físico/veterinária , Estudos Retrospectivos , Taurina/análiseRESUMO
OBJECTIVES: The aim of this pilot study was to assess cardiac troponin I (cTnI) levels in pericardial effusion (PE) and plasma from dogs with PE. BACKGROUND: A reliable marker for detecting the etiology of PE in dogs remains undetermined. cTnI is becoming the gold standard marker for detecting myocardial damage in humans. ANIMALS, MATERIALS AND METHODS: Twenty-five dogs with PE (21 and 4 secondary to neoplasia and non-neoplasia causes, respectively) and 37 control dogs were studied. RESULTS: The median cTnI plasma level from 37 normal dogs versus 15 (out of 25) with PE was 0.03ng/mL and 0.19ng/mL, respectively (p<0.0001). The level of cTnI in PE versus plasma showed a significant correlation (p<0.01) with a Spearman r coefficient of 0.7603. No significant difference could be found upon comparison of dogs with only right atrial tumors (n=14) versus other types of neoplasia (n=7), nor between the group with right atrial tumors (n=14) versus all other cases including neoplasia as well as non-neoplasia (n=11). The median cTnI level in PE from dogs with neoplasia and non-neoplasia was not significantly different. CONCLUSIONS: cTnI did rise significantly in both PE and plasma in dogs with PE, but cTnI levels did not help differentiate between etiologies according to this study. One of the study groups is too small to allow final conclusions, and thus further investigation is warranted.