Authors: Fadia Ali Kamal Kenichi Watanabe Meilei Ma Yuichi Abe Reyad ElBarbary Makoto Kodama Yoshifusa Aizawa
Publish Date: 2010/10/05
Volume: 26, Issue: 1, Pages: 81-90
Abstract
Regardless of the origin injury to the heart can result in cardiomyocyte hypertrophy fibrosis and cell death Myocarditis often progresses to dilated cardiomyopathy DCM a major cause of heart failure In our study we used a rat model of myosininduced experimental autoimmune myocarditis EAM in which the heart transits from an acute phase inflammatory myocarditis to a chronic phase remodeling and DCM Our objective was to investigate whether T3999 a novel phenylpyridazinone can reduce this progression Four weeks after myosin injection T3999 was administered daily to male Lewis rats in two doses 3 and 10 mg/kg orally Four weeks later treatment was terminated hemodynamic and echocardiographic measurements were performed hearts were excised for histopathology and estimation of histamine mRNA and protein levels Mortality rate was reduced by drug treatment T3999 reduced fibrosis and tissue collagen III Profibrotic markers—transforming growth factorβ1 tumor necrosis factorα and galectin3—were attenuated by treatment Mast cell density and degranulation and tissue histamine concentration were also reduced This indicates an antiinflammatory effect of the drug in reducing fibrosis Hypertrophy was reduced as reflected by reduced myocyte diameter and natriuretic peptide expression T3999 treatment increased the sarcoendoplasmic reticulum Ca2+ ATPase 2 protein level and improved several cardiac function parameters The reduction of the remodeling process and improvement in myocardial function suggest an effect of T3999 in attenuating ventricular remodeling in postmyocarditis DCM
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