Effects of Riociguat and Sildenafil in a murine model of chronic right ventricular pressure overload
Abstract
Right heart failure is a prevalent mechanism of cardiovascular collapse and dis-tinctly different from left heart failure. Conventionally, afterload reduction has beenthe main focus to treat right ventricular (RV) dysfunction, but it cannot be achievedin many cases. A new strategy is to directly target RV remodelling. Pulmonaryartery banding (PAB) in mice is used to induce a chronic pressure overload on theRV, without any changes in the pulmonary vasculature.This work addressed two questions: a) the time-course of effects of PAB onright- and left-ventricular (LV) hypertrophy and function, assessed non-invasivelyvia magnetic resonance imaging (MRI). b) Stimulation of the nitric oxide pathwaywas shown to ameliorate maladaptive changes in murine models of chronic LV pres-sure overload. Therefore, the effects of the sGC stimulator Riociguat and the PDE5inhibitor Sildenafil on RV function and fibrosis were investigated.Chronic RV pressure overload was induced by PAB in male C57Bl/6 wild-typemice. For the time-course study, 1, 3, 7, 14, 28, 56 and 105 days after PAB, thefunctional and morphological consequences of sustained pressure overload on the RVand LV were assessed non-invasively using MRI. Additionally, the time-course of theeffects of PAB on cardiomyocyte size and fibrosis was investigated.For the pharmacological intervention study, drug treatment was started sevendays after surgery for 2 weeks. Animals received either 30 mg/kg/d Riociguat peros, Sildenafil 100 mg/kg/d per…
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Evidence Hub reads this as a thesis, done in animal, not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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