Plasmatic Dimethylarginines in Dogs With Myxomatous Mitral Valve Disease

Carlotta Valente; Carlo Guglielmini; Marco Baron Toaldo; Giovanni Romito; Carlo Artusi; Laura Brugnolo; Barbara Contiero; Helen Poser

doi:10.3389/fvets.2021.738898

Plasmatic Dimethylarginines in Dogs With Myxomatous Mitral Valve Disease

Front Vet Sci. 2021 Sep 16:8:738898. doi: 10.3389/fvets.2021.738898. eCollection 2021.

Authors

Carlotta Valente¹, Carlo Guglielmini¹, Marco Baron Toaldo², Giovanni Romito², Carlo Artusi³, Laura Brugnolo³, Barbara Contiero¹, Helen Poser¹

Affiliations

¹ Department of Animal Medicine, Production and Health, University of Padua, Padua, Italy.
² Department of Veterinary Medical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy.
³ Department of Laboratory Medicine, University-Hospital of Padua, Padua, Italy.

Abstract

Plasmatic dimethylarginines, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are considered biomarkers of endothelial and renal dysfunction, respectively, in humans. We hypothesize that plasmatic concentration of dimethylarginines in dogs with myxomatous mitral valve disease (MMVD) is influenced by heart disease stage. Eighty-five client-owned dogs with MMVD, including 39, 19, and 27 dogs in ACVIM stages B1, B2, and C+D, respectively, and a control group of 11 clinically healthy dogs were enrolled. A prospective, multicentric, case-control study was performed. Each dog underwent a complete clinical examination, arterial blood pressure measurement, thoracic radiography, six-lead standard electrocardiogram, transthoracic echocardiography, CBC, biochemical profile, and urinalysis. Plasmatic concentration of dimethylarginines was determined through high-performance liquid chromatography coupled with tandem mass spectrometry. Median ADMA was significantly increased in dogs of group C+D (2.5 μmol/L [2.1-3.0]) compared to those of group B1 (1.8 μmol/L [1.6-2.3]; p < 0.001) and healthy dogs (1.9 μmol/L [1.7-2.3]; p = 0.02). Median SDMA was significantly increased in dogs of group C+D (0.7 μmol/L [0.5-0.9]) compared to those of groups B1 (0.4 μmol/L [0.3-0.5]; p < 0.001), B2 (0.4 μmol/L [0.3-0.6]; p < 0.01), and the control group (0.4 μmol/L [0.35-0.45]; p = 0.001). In the final multivariable analysis, ADMA and SDMA were significantly associated with left atrium to aorta ratio (p < 0.001), and creatinine (p < 0.001), respectively. Increased plasmatic concentrations of dimethylarginines suggest a possible role as biomarkers of disease severity in dogs with decompensated MMVD.

Keywords: ADMA; SDMA; arginine; canine; dimethylarginines; heart failure.