Exercise Training Attenuates Right Ventricular Remodeling in Rats with Pulmonary Arterial Stenosis

Brunno Lemes De Melo,Paulo De Tarso C De Carvalho,Leslie A Portes,Luís F N Dos Santos,Helenita A De Oliveira,Regiane S Feliciano,Ednei L Antônio,José A Silva,Stella S Vieira,Paulo J F Tucci,Andrey J Serra

doi:10.3389/fphys.2016.00541

Brunno Lemes De Melo, Paulo De Tarso C De Carvalho + Show 9 more

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https://doi.org/10.3389/fphys.2016.00541

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Introduction: Pulmonary arterial stenosis (PAS) is a congenital defect that causes outflow tract obstruction of the right ventricle (RV). Currently, negative issues are reported in the PAS management: not all patients may be eligible to surgeries; there is often the need for another surgery during passage to adulthood; patients with mild stenosis may have later cardiac adverse repercussions. Thus, the search for approaches to counteract the long-term PAS effects showed to be a current target. At the study herein, we evaluated the cardioprotective role of exercise training in rats submitted to PAS for 9 weeks.Methods and Results: Exercise resulted in improved physical fitness and systolic RV function. Exercise also blunted concentric cavity changes, diastolic dysfunction, and fibrosis induced by PAS. Exercise additional benefits were also reported in a pro-survival signal, in which there were increased Akt1 activity and normalized myocardial apoptosis. These findings were accompanied by microRNA-1 downregulation and microRNA-21 upregulation. Moreover, exercise was associated with a higher myocardial abundance of the sarcomeric protein α-MHC and proteins that modulate calcium handling—ryanodine receptor and Serca 2, supporting the potential role of exercise in improving myocardial performance.Conclusion: Our results represent the first demonstration that exercise can attenuate the RV remodeling in an experimental PAS. The cardioprotective effects were associated with positive modulation of RV function, survival signaling pathway, apoptosis, and proteins involved in the regulation of myocardial contractility.

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Pulmonary arterial stenosis (PAS) is a congenital defect that causes outflow tract obstruction of the right ventricle (RV)
We evaluated whether an aerobic exercise training would improve functional capacity and attenuate the RV remodeling in an experimental PAS model
It is true that the stenosis degree could result in very dissimilar RV afterload during the study, thereby a bias would be set

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Introduction

Pulmonary arterial stenosis (PAS) is a congenital defect that causes outflow tract obstruction of the right ventricle (RV). Pulmonary arterial stenosis (PAS) is a common congenital heart disease that affects the RV outflow tract (Bonow et al, 2008; Tarasoutchi et al, 2011; Ananthakrishna et al, 2014), in which has been highly prevalent in women (Egbe et al, 2014). A mild RV obstruction is often only clinically supervised (Kan et al, 1982; Rey et al, 1988; Stanger et al, 1990) In this regard, a possible hypertrophy and functional RV abnormality is monitored in the long-term as a means to prevent advance to heart failure (Pokreisz et al, 2007; Kittipovanonth et al, 2008; Baumgartner et al, 2010). In the knowledge of the natural history of PAS, data are showing that mild cases can become severe at a later date (Anand and Mehta, 1997; Baumgartner et al, 2010)

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