Treatment of dogs with compensated myxomatous mitral valve disease with spironolactone-a pilot study

Spironolactone improves outcome in dogs with advanced myxomatous mitral valve disease (MMVD). Its efficacy in preclinical MMVD is unknown. The hypothesis was the administration of spironolactone to dogs with compensated MMVD demonstrating risk factors for poorer prognosis will decrease the rate of disease progression. The aim was to provide pilot data to evaluate preliminary effects and sample size calculation for a definitive clinical trial

Differentiation of Cardiac from Noncardiac Pleural Effusions in Cats using Second-Generation Quantitative and Point-of-Care NT-proBNP Measurements

BACKGROUND: Pleural effusion is a common cause of dyspnea in cats. N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) measurement, using a first‐generation quantitative ELISA, in plasma and pleural fluid differentiates cardiac from noncardiac causes of pleural effusion. HYPOTHESIS/OBJECTIVES: To determine whether NT‐proBNP measurements using second‐generation quantitative ELISA and point‐of‐care (POC) tests in plasma and pleural fluid distinguish cardiac from noncardiac pleural effusions and how results compare to the first‐generation ELISA. ANIMALS: Thirty‐eight cats (US cohort) and 40 cats (UK cohort) presenting with cardiogenic or noncardiogenic pleural effusion. METHODS: Prospective cohort study. Twenty‐one and 17 cats in the US cohort, and 22 and 18 cats in the UK cohort were classified as having cardiac or noncardiac pleural effusion, respectively. NT‐proBNP concentrations in paired plasma and pleural fluid samples were measured using second‐generation ELISA and POC assays. RESULTS: The second‐generation ELISA differentiated cardiac from noncardiac pleural effusion with good diagnostic accuracy (plasma: sensitivity, 95.2%, specificity, 82.4%; pleural fluid: sensitivity, 100%, specificity, 76.5%). NT‐proBNP concentrations were greater in pleural fluid (719 pmol/L (134–1500)) than plasma (678 pmol/L (61–1500), P = 0.003), resulting in different cut‐off values depending on the sample type. The POC test had good sensitivity (95.2%) and specificity (87.5%) when using plasma samples. In pleural fluid samples, the POC test had good sensitivity (100%) but low specificity (64.7%). Diagnostic accuracy was similar between first‐ and second‐generation ELISA assays. CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of NT‐proBNP using a quantitative ELISA in plasma and pleural fluid or POC test in plasma, but not pleural fluid, distinguishes cardiac from noncardiac causes of pleural effusion in cats

Exploring early life events including diet in cats presenting for gastrointestinal signs in later life

Our study aimed to determine if certain early life events were more prevalent in cats presenting to veterinary practices specifically for gastrointestinal signs on at least two occasions between six months and 30 months of age. Data from an owner-completed questionnaire for 1212 cats before 16 weeks of age and subsequent questionnaires for the same cats between six months and 30 months of age were reviewed. Of the 1212 cats included, 30 visited a veterinary practice for gastrointestinal signs on two or more occasions. Of the early life events recorded, cats reported with vomiting, diarrhoea or both, and/or those not exclusively fed commercial diet(s) that meets the World Small Animal Veterinary Association (WSAVA) Global Nutrition Committee (GNC) guidelines before 16 weeks of age were more likely to visit veterinary practices specifically for gastrointestinal signs on at least two occasions between six months and 30 months of age (P<0.001, odds ratio (OR)=2.64, 95 per cent confidence interval (CI)=1.66–4.22 and P=0.030, OR=1.51, 95 per cent CI=1.04–2.22, respectively). Ensuring cats exclusively consume commercial diet(s) that meets the WSAVA GNC guidelines and further studies identifying specific aetiologies for vomiting and diarrhoea before 16 weeks of age to enable prevention may reduce the number of cats subsequently presenting to primary care veterinary practices for repeated gastrointestinal signs

Prevalence of gastroesophageal reflux in dogs undergoing MRI for a thoracolumbar vertebral column pathology

Objectives: The aims of the study were to investigate the prevalence and extent of gastroesophageal reflux, and the prevalence of regurgitation in dogs undergoing thoracolumbar spine magnetic resonance imaging, and to explore possible associations of reflux and regurgitation with signalment (breed, age, sex, neuter status), bodyweight, body condition score and drugs used in the anaesthetic protocol. Materials and Methods: The thoracic part of the oesophagus was retrospectively assessed for presence and quantification of fluid on two T2 weighted sequences. Patient breed, age, sex, neuter status, weight and body condition score were recorded. Anaesthetic records were reviewed for the presence of regurgitation and detailed anaesthetic protocols. Results: Fifty percent [95% confidence interval (44.99, 56.81)] of included dogs had evidence of gastroesophageal reflux. Reflux was not associated with the individual breed, age, sex, neuter status or body weight. Brachycephalic dogs did not demonstrate significantly higher rates of reflux compared to non-brachycephalic dogs. A larger volume of reflux was associated with a higher chance of regurgitation. Clinical Significance: Gastroesophageal reflux is a common finding in dogs undergoing thoracolumbar spine magnetic resonance imaging. Dogs which regurgitated had higher volumes of reflux. Early detection and quantification of the volume of reflux is helpful as it may allow the anaesthetist to take measures which may reduce the risk of associated complications

Computer simulation of syringomyelia in dogs

Syringomyelia is a pathological condition in which fluid-filled cavities (syringes) form and expand in the spinal cord. Syringomyelia is often linked with obstruction of the craniocervical junction and a Chiari malformation, which is similar in both humans and animals. Some brachycephalic toy breed dogs such as Cavalier King Charles Spaniels (CKCS) are particularly predisposed. The exact mechanism of the formation of syringomyelia is undetermined and consequently with the lack of clinical explanation, engineers and mathematicians have resorted to computer models to identify possible physical mechanisms that can lead to syringes. We developed a computer model of the spinal cavity of a CKCS suffering from a large syrinx. The model was excited at the cranial end to simulate the movement of the cerebrospinal fluid (CSF) and the spinal cord due to the shift of blood volume in the cranium related to the cardiac cycle. To simulate the normal condition, the movement was prescribed to the CSF. To simulate the pathological condition, the movement of CSF was blocked

Endothelial glycocalyx is damaged in diabetic cardiomyopathy: angiopoietin 1 restores glycocalyx and improves diastolic function in mice

Aims/hypothesis: Diabetic cardiomyopathy (DCM) is a serious and under-recognised complication of diabetes. The first sign is diastolic dysfunction, which progresses to heart failure. The pathophysiology of DCM is incompletely understood but microcirculatory changes are important. Endothelial glycocalyx (eGlx) plays multiple vital roles in the microcirculation, including in the regulation of vascular permeability, and is compromised in diabetes but has not previously been studied in the coronary microcirculation in diabetes. We hypothesised that eGlx damage in the coronary microcirculation contributes to increased microvascular permeability and hence to cardiac dysfunction. Methods: We investigated eGlx damage and cardiomyopathy in mouse models of type 1 (streptozotocin-induced) and type 2 (db/db) diabetes. Cardiac dysfunction was determined by echocardiography. We obtained eGlx depth and coverage by transmission electron microscopy (TEM) on mouse hearts perfusion-fixed with glutaraldehyde and Alcian Blue. Perivascular oedema was assessed from TEM images by measuring the perivascular space area. Lectin-based fluorescence was developed to study eGlx in paraformaldehyde-fixed mouse and human tissues. The eGlx of human conditionally immortalised coronary microvascular endothelial cells (CMVECs) in culture was removed with eGlx-degrading enzymes before measurement of protein passage across the cell monolayer. The mechanism of eGlx damage in the diabetic heart was investigated by quantitative reverse transcription-PCR array and matrix metalloproteinase (MMP) activity assay. To directly demonstrate that eGlx damage disturbs cardiac function, isolated rat hearts were treated with enzymes in a Langendorff preparation. Angiopoietin 1 (Ang1) is known to restore eGlx and so was used to investigate whether eGlx restoration reverses diastolic dysfunction in mice with type 1 diabetes. Results: In a mouse model of type 1 diabetes, diastolic dysfunction (confirmed by echocardiography) was associated with loss of eGlx from CMVECs and the development of perivascular oedema, suggesting increased microvascular permeability. We confirmed in vitro that eGlx removal increases CMVEC monolayer permeability. We identified increased MMP activity as a potential mechanism of eGlx damage and we observed loss of syndecan 4 consistent with MMP activity. In a mouse model of type 2 diabetes we found a similar loss of eGlx preceding the development of diastolic dysfunction. We used isolated rat hearts to demonstrate that eGlx damage (induced by enzymes) is sufficient to disturb cardiac function. Ang1 restored eGlx and this was associated with reduced perivascular oedema and amelioration of the diastolic dysfunction seen in mice with type 1 diabetes. Conclusions/interpretation: The association of CMVEC glycocalyx damage with diastolic dysfunction in two diabetes models suggests that it may play a pathophysiological role and the enzyme studies confirm that eGlx damage is sufficient to impair cardiac function. Ang1 rapidly restores the CMVEC glycocalyx and improves diastolic function. Our work identifies CMVEC glycocalyx damage as a potential contributor to the development of DCM and therefore as a therapeutic target