Characterization of the spontaneous degenerative mitral valve disease in FVB mice.

BACKGROUND: The development of new non-surgical treatments dedicated to mitral valve degeneration is limited by the absence of relevant spontaneous and rapidly progressing animal experimental models. ANIMALS: We characterized the spontaneous mitral valve degeneration in two inbred FVB mouse strains compared to C57BL/6J and investigated a contribution of the serotonergic system. METHODS: Males and females FVB/NJ and FVB/NRj were compared to the putative C57BL/6J control at 12, 16, 20 and 24 weeks of age. Body weight, systolic blood pressure, heart rate, urinary 5-hydroxyindoleacetic acid (5-HIAA), whole blood and plasma serotonin, tail bleeding time, blood cell count, plasma TGF-ß1 and plasma natriuretic peptide concentrations were measured. Myocardium and mitral valves were characterized by histology. mRNA mitral expression of 5-HT2A and 5-HT2B receptors was measured in the anterior leaflet. Cardiac anatomy and function were assessed by echocardiography. RESULTS: Compared to C57BL/6J, FVB mice strains did not significantly differ regarding body weight increase, arterial blood pressure and heart rate. A progressive augmentation of plasma pro-ANP was observed in FVB mice. Nevertheless, no cardiac hypertrophy or left-ventricular fibrosis were observed. Accordingly, plasma TGF-ß1 was not different among the three strains. Conversely, FVB mice demonstrated a high prevalence of fibromyxoid highly cellularized and enriched in glycosaminoglycans lesions, inducing major mitral leaflets thickening without increase in length. The increased thickness was correlated with urinary 5-HIAA and blood platelet count. Whole blood serotonin concentration was similar in the two strains but, in FVB, a reduction of plasma serotonin was observed together with an increase of the bleeding time. Finally, echocardiography identified left atrial and left ventricular remodeling associated with thickening of both mitral leaflets and mitral insufficient in 30% of FVB mice but no systolic protrusion of mitral leaflets towards the atrium. CONCLUSION: The FVB mouse strain is highly prone to spontaneous mitral myxomatous degeneration. A contribution of the peripheral serotonergic system is suggested.

Evaluation of plasma and urinary levels of 6-keto-prostaglandin F1alpha as a marker for asymptomatic myxomatous mitral valve disease in dogs.

Endothelial dysfunction might be involved in the pathogenesis of myxomatous mitral valve disease (MMVD). The aims of this study were (1) to validate an enzyme immunoassay (EIA) for canine 6-keto-prostaglandin (PG)F(1alpha) (prostacyclin metabolite and marker for endothelial function) and (2) to compare plasma and urinary 6-keto-PGF(1alpha) in dogs with asymptomatic MMVD. The study included two breeds predisposed to MMVD and two control groups (Cairn terriers and dogs of different breeds). Echocardiography was used to estimate the severity of MMVD. The intra- and inter-assay coefficients of variation were between 3.1% and 24.5% in the assay range. No echocardiographic parameter was correlated with plasma or urinary 6-keto-PGF(1alpha) (P>0.05), but all control dogs had lower urinary 6-keto-PGF(1alpha) (P<0.02) and the Cairn terriers had higher plasma 6-keto-PGF(1alpha) (P<0.02). The EIA appeared valid for measuring canine 6-keto-PGF(1alpha) in plasma and urine. It is suggested that 6-keto-PGF(1alpha) levels are related to breed and not MMVD in asymptomatic stages.

[The sympathetic-adrenal system in mitral heart defects in patients of different ages studied by the use of a specific L-DOPA test]. / Izuchenie simpatiko-adrenalovoi sistemy pri mitral'nykh porokakh serdtsa u bol'nykh raznogo vozrasta s primeneniem spetsificheskogo testa s L-DOFA.

As many as 59 patients aged 35 to 74 years suffering from mitral valvular disease (MVD) were examined for excretion of dopamine (DA), noradrenaline (NA) and adrenaline, parameters indicating the activity of the sympathoadrenal system. Administration of L-DOPA brought about a significant increase of excretion of all catecholamines in all the patients under 59 years and in those aged 60 to 74 years. In patients with stage I and IIA heart failure, DA excretion rose 50-fold in response to L-DOPA administration, in those with stage IIB and III, 17-fold (p less than 0.001). In patients suffering from MVD, no age-associated differences were revealed in the levels of catecholamines and ICM. In patients suffering from MVD with the predominance of stenosis and in those with stage I and IIA heart failure, background excretion of NA was significantly higher than in patients suffering from MVD with the predominance of heart failure (p less than 0.01). Administration of L-DOPA was followed by an appreciable increment of NA exactly in patients suffering from MVD with the predominance of stenosis (p less than 0.001). In the majority of patients with stage III heart failure refractory to multimodality treatment, the L-DOPA test revealed the smallest increment of DA; its excretion rose only 12-fold. Therefore, the progress of heart failure entails a decrease of the reserve potentialities of the sympathoadrenal system, marked by less output of its mediators.