Chronic Degenerative Valvular Disease Research Articles

Anti-inflammatory properties and expression in selected organs of canine interleukin-1β splice variant 1

The IL-1β gene can be also be spliced with the intron 4 retention; the result is a IL-1β splice variant 1 (IL-1βsv1), which was significantly up-regulated in failing myocardium of dogs suffering from chronic degenerative valvular disease (CDVD). Expression of IL-1βsv1 was assessed, at both RNA and protein levels, in organs affected by heart failure, namely, kidneys, liver, and lungs from 35 dogs suffering chronic degenerative valvular disease (CDVD) and in 20 disease free control dogs. IL-1βsv1 RNA was detected in the dogs from both groups. In the CDVD group, the highest RNA and protein IL-1βsv1 levels were observed in lungs, followed, in that order, by the liver and kidneys. IL-1βsv1 protein was found in the cytoplasm of hepatocytes and IL-1βsv1-overexpressing DH82 cells. In lungs, IL-1βsv1 was localized in the cytoplasm and in the nuclei of bronchiolar epithelial and smooth-muscle cells. Cytoplasmic and nuclear IL-1βsv1 expression was observed in macrophages, and a strong nuclear signal was detected in epithelial cells of the alveolar sacs. Following lipopolysaccharide (LPS) stimulation, overexpression of IL-1βsv1 in DH82 cells decreased the pro-inflammatory response. Our results indicate that IL-1βsv1 is constitutively expressed in both normal tissues and in tissues from cases of heart failure. The presence of IL-1βsv1 in tissues exposed to invading agents and its anti-inflammatory activity in DH82 cells may point to its immunomodulatory role in vivo.

Plasma miRNAs as potential biomarkers of chronic degenerative valvular disease in Dachshunds.

BackgroundEndocardiosis is the most common heart disease in Dachshunds and is therefore an important cause of cardiac morbidity and death. In recent years we have observed an increasing interest in the development of new genetic and genomic markers of heart disease. The discovery of miRNAs circulating in biofluids such as plasma or serum aroused researchers’ interest in using them as potential biomarkers. In the present study we analysed the expression of 9 miRNAs described in literature as being involved in cardiovascular pathology in the plasma of dogs suffering from endocardiosis.ResultsExpression analysis using the Real-time PCR method revealed that two out of nine miRNAs were significantly downregulated: the expression of miR-30b differed between ACVIM stage B and stage A (control) dogs; the expression of mi-133b differed ACVIM stage C and stage A dogs. 5 miRNAs (miR-125, miR-126, miR-21, miR-29b and miR-30b) showed a trend of downregulation in the ACVIM C group. Levels of miR-423 were the same in healthy and diseased dogs. Expression of miR-208a and 208b was not detected.ConclusionsmiR-30b could be a potential biomarker of ACVIM stage B heart failure in Dachshunds with endocardiosis and miR-133b could be a potential biomarker of ACVIM stage C. The lack of expression or lack of significant changes in expression in 7 miRNAs which are potential biomarkers of heart diseases in humans proves that findings from human medicine are not always directly reflected in veterinary medicine.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-014-0205-8) contains supplementary material, which is available to authorized users.

Red blood cell distribution width in dogs with chronic degenerative valvular disease

To evaluate RBC distribution width (RDW) in dogs with chronic degenerative valvular disease (CDVD) with compensated or decompensated heart failure. Retrospective case-control study. 27 healthy dogs and 135 dogs with CDVD (87 dogs with compensated heart failure and 48 dogs with decompensated heart failure). The RDW and various CBC and serum biochemical variables were compared among groups. Correlations between RDW and various echocardiographic variables were evaluated. Mean ± SD RDW in dogs with CDVD (13.1% ± 1.0%) was not significantly different from that of healthy dogs (12.8% ± 0.8%). The RDW of dogs with CDVD and compensated heart failure (13.0% ± 1.0%) was not significantly different from that of dogs with CDVD and decompensated heart failure (13.2% ± 1.1%). The RDW had a significant, weak, negative correlation with Hct (correlation coefficient, -0.250), hemoglobin concentration (correlation coefficient, -0.219), and mean corpuscular volume (correlation coefficient, -0.211). The RDW had a significant, weak, positive correlation with 1 echocardiographic index of CDVD severity (ie, the left atrium-to-aorta ratio [correlation coefficient, 0.183]). In this study population, RDW did not seem to be associated with the presence of heart failure or CDVD.

An Assessment of Left Ventricular Systolic Function with the Use of a Continuous Doppler Imaging in Dogs with Spontaneous Mitral Regurgitation. A Preliminary Study

Abstract The aim of this study was to evaluate systolic function of left ventricle in dogs with spontaneous mitral regurgitation by estimating the rate of pressure rise in the left ventricle (dP/dt). Ninety-three dogs of different breed and sex, with chronic degenerative valvular disease were examined. All dogs had echocardiography examination with dP/dt estimation assessed from mitral regurgitant jet using continuous Doppler-echocardiography. The dogs were divided into four classes of heart failure according to NYHA class. Results: dogs in NYHA I dP/dt = 2,142 ±1,309, SF=33.6±10.5, EF=66.58± 14; NYHA II dP/dt = 3,062 ±1,798, SF=42 ±10, EF=76.5 ±11.5; NYHA III dP/dt = 3,483 ±2,136, SF=44.2 ±21, EF=75.7 ±13; NYHA IV dP/dt = 4,496 ±1,797, SF=40.6 ±6, EF=70.4 ±16. Dogs with chronic cardiac insufficiency and mitral insufficiency due to chronic degenerative valvular disease had no echocardiograhic evidence of left ventricular systolic dysfunction assessed from mitral regurgitant jet dP/dt.

The Anatomical Basis of Bradycardia–Tachycardia Syndrome in Elderly Dogs with Chronic Degenerative Valvular Disease

The hearts of seven elderly dogs in which bradycardia-tachycardia syndrome (BTS) had been diagnosed electrocardiographically were examined post mortem. The clinical basis of the underlying heart disease was invariably mitral or mitral and tricuspid regurgitation. Microscopical examination of the sinoatrial (SA) node and the SA junctional region consistently revealed depletion of SA nodal cells, with a corresponding increase in fibrous or fibro-fatty tissue that interrupted contiguity between the SA node and the surrounding atrial myocardium. The left and right atrial walls showed an increased amount of fibrous tissue in the myocardium and disruption of the muscle bundle architecture (interstitial myocardial fibrosis) to varying degrees. Qualitatively, these changes in the SA node and the SA node region resembled those associated with ageing in elderly people with or without BTS. Thus, it is possible that the pathological process affecting the SA node in these dogs was fundamentally related to ageing and may have caused BTS, in combination with atrial myocardial lesions caused by mitral and tricuspid regurgitation.

IMAGING DIAGNOSIS-INTRAPERICARDIAL RIGHT AURICLE ANEURYSM IN A DOG

An 11-year-old, male, Pekinese was examined because of a sporadic, nonresponsive, nonproductive cough. Radiographically there was cardiomegaly and a soft tissue mass in the cranial mediastinum. Echocardiographically, chronic degenerative valvular disease was diagnosed. Furthermore, a large anechoic structure located cranial to the right atrium was detected. Computed tomography was performed to define the mediastinal mass and a right auricle aneurysm was diagnosed. The dog died suddenly 1 day after the diagnostic imaging procedures. At necropsy, a right auricular aneurysm without discontinuity of the pericardial sac was confirmed. Intrapericardial right auricular aneurysm should be included in the differential diagnoses of cranial mediastinal masses.

Chronic degenerative valvular disease – where are we now?

Chronic degenerative valvular disease – where are we now?

Can ventricular function be assessed by echocardiography in chronic canine mitral valve disease?

Mitral regurgitation (MR) related to chronic degenerative valvular disease is the most important cause of heart failure in dogs. Ultrasound examination of the heart can identify valve lesions, confirm the presence of valvular regurgitation, document cardiac remodeling, estimate intracardiac pressures, and quantify systolic ventricular function. These findings can influence prognosis or selection of medical therapy. Reductions in ventricular systolic function may be detected on serial echocardiographic examinations in some dogs with MR. However the changes in ventricular loading that accompany MR often complicate these measurements. For example, shortening and ejection fractions are often increased in severe MR, even in the setting of congestive heart failure. Echocardiography with Doppler is also used to assess ventricular diastolic function and filling pressures. This information helps predict the risk of congestive heart failure. However these findings are often rendered ambiguous by age-related impairment of ventricular relaxation, elevations in left atrial pressure due to MR, and effects of volume overload on myocardial tissue velocities. These factors limit the usefulness of ventricular filling and tissue velocities, as well as derived ratios such as the E/E' ratio, for predicting congestive heart failure in MR. More advanced Doppler and tissue echocardiographic methods, as well as prospective clinical studies, are needed to reduce the ambiguity involved with assessment of ventricular function and filling pressures in the setting of MR.

Increased expression of interleukin-1β and its novel splice variant in canine hearts with volume overload

Volume overload frequently caused in dogs by chronic degenerative valvular disease (CDVD), eventually leads to cardiac failure. Experimental and clinical evidences demonstrate that increased interleukin-1β serum level in patients with heart insufficiency correlates with the severity of failure irrespective of its etiology. Very little is known about the IL-1β expression in failing vs. non-failing myocardium. IL-1β transcript level was determined in the CDVD dogs ( n = 17) and control animals ( n = 9) without cardiac insufficiency by real-time PCR. IL-1β transcript level in failing hearts was higher than in the control. In both groups the highest IL-1β level was detected in the left ventricles. Although IL-1β is a major pro-inflammatory cytokine most of the CDVD dogs displayed no inflammatory infiltrates into the myocardium. Massive fibrosis was observed in the control group, unlike the failing hearts, in which cardiomyocyte hypertrophy and atrophy dominated. The alternative IL-1β transcript identified here (IL-1βsv1) was significantly elevated in the failing myocardium compared with the control group. Increased IL-1β expression seems to be associated with mechanical heart overload. Its endogenous origin, and certain histopathological findings attributed to IL-1β indicate its importance in cardiac hypertrophy and failure. The lack of some typical IL-1β actions, i.e. inflammatory, pyrogenic and fibrotic, may suggest a different role of this cytokine in myocardium. It appears that the canine IL-1β gene can be transcribed in two ways in heart tissue, with the IL-1βsv1 form present mainly in failing hearts.

Pimobendan in Heart Failure Therapy – A Silver Bullet?

Pimobendan is a novel agent with properties that are highly desirable in the clinical management of congestive heart failure (CHF) secondary to both dilated cardiomyopathy (DCM) and chronic degenerative valvular disease in dogs. Review of available data suggests that pimobendan is safe, well tolerated, and leads to enhanced quality of life in dogs with CHF secondary to DCM or chronic valvular disease when used in combination with furosemide or other conventional therapies (e.g., angiotensin-converting enzyme inhibitors, digoxin). Pimobendan leads to a reduction in mortality from CHF associated with DCM, and ongoing studies are evaluating its effects on mortality associated with chronic valvular disease.