Figure 1: SIL Controlled LV Dysfunction and Cardiac Remodeling in Chagasic Mice

C57BL/6 mice were infected with Trypanosoma cruzi (Tc), and treated with sildenafil (SIL) for 3 weeks, beginning at day 45 post-infection (pi). Peripheral blood and heart tissues were collected at 150 days pi. (A) Shown are the myocardial levels of cGMP-dependent protein kinase activity (PKG) (a), PDE5 mRNA by real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) (b), and PDE5 protein level by Western blotting (c). Densitometry units for PDE5 were normalized to GAPDH (B) transthoracic echocardiography was performed by using a Vevo 2100 System. Shown are (a) stroke volume, (b) cardiac output, (c) ejection fraction, (d) fractional shortening, and (e) left ventricular (LV) posterior wall thickness at diastole (LVPW). (C) Heart tissue sections were stained with Mason’s Trichrome (a–c, magnification 20×), and scored for fibrosis (d) as described in Materials and Methods. (D) Quantitative RT-PCR analysis of mRNA levels for collagen isoforms COLI and COLIII (a and b) and SERCA2 (c) in heart tissue of chronically infected (±SIL) mice. In all figures, data are plotted as mean ± SEM (n = 6 to 8 mice per group). Significance is shown with an asterisk (Tc-infected vs. matched control) or hash mark (infected/untreated vs. infected/SIL-treated), and presented as *,#p < 0.05, **,##p < 0.01, ***,###p < 0.001. Mason’s T = Mason’s Trichrome; Nor = normal.