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- Author or Editor: Mark A. Oyama x
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Abstract
Objective—To evaluate global genome expression patterns of left ventricular tissues from dogs with dilated cardiomyopathy (DCM).
Sample Population—Tissues obtained from the left ventricle of 2 Doberman Pinschers with end-stage DCM and 5 healthy control dogs.
Procedure—Transcriptional activities of 23,851 canine DNA sequences were determined by use of an oligonucleotide microarray. Genome expression patterns of DCM tissue were evaluated by measuring the relative amount of complementary RNA hybridization to the microarray probes and comparing it with gene expression for tissues from 5 healthy control dogs.
Results—478 transcripts were differentially expressed (≥ 2.5-fold change). In DCM tissue, expression of 173 transcripts was upregulated and expression of 305 transcripts was downregulated, compared with expression for control tissues. Of the 478 transcripts, 167 genes could be specifically identified. These genes were grouped into 1 of 8 categories on the basis of their primary physiologic function. Grouping revealed that pathways involving cellular energy production, signaling and communication, and cell structure were generally downregulated, whereas pathways involving cellular defense and stress responses were upregulated. Many previously unreported genes that may contribute to the pathophysiologic aspects of heart disease were identified.
Conclusions and Clinical Relevance—Evaluation of global expression patterns provides a molecular portrait of heart failure, yields insights into the pathophysiologic aspects of DCM, and identifies intriguing genes and pathways for further study. (Am J Vet Res 2005;66:1140–1155)
Abstract
Objective—To evaluate global genome expression patterns of mitral valve tissues from dogs with degenerative mitral valve disease (DMVD).
Sample Population—Anterior mitral valve leaflets of 4 dogs with severe DMVD and 4 healthy control dogs.
Procedures—Transcriptional activities of 23,851 canine DNA sequences were determined by use of an oligonucleotide microarray. Genome expression patterns of tissue from dogs with DMVD were evaluated by measuring the relative amount of complementary RNA hybridization to the microarray probes and by comparing it with gene expression from healthy control dogs.
Results—229 transcripts were differentially expressed (≥ 2-fold change). In dogs with DMVD, expression of 159 transcripts was upregulated and expression of 70 transcripts was downregulated. Of the 229 transcripts, 152 genes could be specifically identified. These genes were grouped into 1 of 9 categories on the basis of their primary physiologic function. Grouping revealed that pathways involving cell signaling, inflammation, extracellular matrix, immune function, cell defense, and metabolism were generally upregulated. Inflammatory cytokines and the serotonin-transforming growth factor-β pathway were identified as contributory to the pathophysiologic aspects of DMVD.
Conclusions and Clinical Relevance—Evaluation of global expression patterns provides a molecular portrait of mitral valve disease, yields insight into the pathophysiologic aspects of DMVD, and identifies intriguing genes and pathways for further study.
Abstract
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.
Abstract
OBJECTIVE
To identify associations between admission variables, Animal Trauma Triage (ATT) score, and Modified Glasgow Coma Scale (MGCS) score with need for transfusion or surgical interventions and survival to discharge in cats with bite wounds.
ANIMALS
1,065 cats with bite wounds.
PROCEDURES
Records of cats with bite wounds were obtained from the VetCOT registry from April 2017 to June 2021. Variables included point of care laboratory values, signalment, weight, illness severity scores, and surgical intervention. Associations between admission parameters, terciles of MGCS, quantiles of ATT scores, and death or euthanasia were assessed using univariable and multivariable logistic regression analysis.
RESULTS
872 cats (82%) survived to discharge, while 170 (88%) were euthanized and 23(12%) died. In the multivariable model, age, weight, surgical treatment, ATT and MGCS scores were associated with nonsurvival. For every 1 year of age, odds of nonsurvival increased by 7% (P = .003) and for every 1 kg of body weight, odds of nonsurvival decreased by 14% (P = .005). Odds of dying increased with lower MGCS and higher ATT scores (MGCS: 104% [95% CI, 116% to 267%; P < .001]; ATT: 351% [95% CI, 321% to 632%; P < .001). Odds of dying decreased by 84% (P < .001) in cats that underwent surgery versus those that did not.
CLINICAL RELEVANCE
This multicenter study indicated association of higher ATT and lower MGCS with worse outcome. Older age increased the odds of nonsurvival, while each kilogram increase in bodyweight decreased odds of nonsurvival. To our knowledge, this study is the first to describe associations of age and weight with outcome in feline trauma patients.
Abstract
Objective—To determine whether serum N-terminal pro-B-type natriuretic (NT-proBNP) concentration could be used to identify cardiac disease in dogs and to assess disease severity in affected dogs.
Design—Cross-sectional study.
Animals—119 dogs with mitral valve disease, 18 dogs with dilated cardiomyopathy, and 40 healthy control dogs.
Procedures—Serum NT-proBNP concentration was measured with an ELISA validated for use in dogs. Results of physical examination, thoracic radiography, echocardiography, and serum biochemical analyses were recorded for dogs with cardiac disease.
Results—Serum NT-proBNP concentration was significantly higher in dogs with cardiac disease than in control dogs, and a serum NT-proBNP concentration > 445 pmol/L could be used to discriminate dogs with cardiac disease from control dogs with a sensitivity of 83.2% and specificity of 90.0%. In dogs with cardiac disease, serum NT-proBNP concentration was correlated with heart rate, respiratory rate, echocardiographic heart size, and renal function. For dogs with cardiac disease, serum NT-proBNP concentration could be used to discriminate dogs with and without radiographic evidence of cardiomegaly and dogs with and without congestive heart failure.
Conclusions and Clinical Relevance—Results suggested that serum NT-proBNP concentration may be a useful adjunct clinical test for diagnosing cardiac disease in dogs and assessing the severity of disease in dogs with cardiac disease.
Abstract
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 ≥ 2-fold between groups were analyzed by matrixassisted 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.
Abstract
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 matrixassisted 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.
