Histological and haemodynamic characterization of right ventricle in sedentary and trained rats with heart failure with preserved ejection fraction

Autores da FMUP

• Sara Vanessa Amorim Leite

  Autor

• António Sousa Barros

  Autor

• André Pedro Leite Martins Lourenço

  Autor

• Cláudia Cristiana Sousa Mendes

  Autor

• Cristine Schmidt

  Autor

• Joaquim Adelino Correia Ferreira Leite Moreira

  Autor

Participantes de fora da FMUP

• Oliveira, MI
• Santos, M
• Moreira-Gonçalves, D

Unidades de investigação

• Cirurgia e Fisiologia

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

Abstract

New Findings What is the central question of this study? Right ventricle (RV) dysfunction is highly prevalent in heart failure with preserved ejection fraction (HFpEF), nearly doubling the risk of death: what are the RV functional and structural changes in HFpEF and how does aerobic exercise impact them? What is the main finding and its importance? The HFpEF ZSF1 rat model presents RV structural and functional changes mimicking the human condition. Aerobic exercise prevented the decline in V?O2max, lowered surrogate markers of RV overload (e.g., higher mean and maximum systolic pressure) and improved diastolic dysfunction (e.g., end-diastolic pressure and relaxation time constant). This emphasizes the importance of using exercise to manage HFpEF. Right ventricle (RV) dysfunction is highly prevalent in heart failure with preserved ejection fraction (HFpEF) and is a marker of poor prognosis. We assessed the obese ZSF1 rat model of HFpEF to ascertain if these animals also develop RV dysfunction and evaluated whether aerobic exercise could prevent this. Obese ZSF1 rats were randomly allocated to an aerobic exercise training group (n = 7; treadmill running, 5 days/week, 60 min/day, 15 m/min for 5 weeks) or to a sedentary group (n = 7). We used lean ZSF1 rats (n = 7) as the control group. After 5 weeks, rats were submitted to an exercise tolerance test and invasive haemodynamic evaluation, killed and samples from the RV collected for histological analysis. Obese sedentary ZSF1 rats showed lower V?O2max, RV pressure overload (e.g., higher mean and maximum systolic pressure) and diastolic dysfunction (e.g., higher minimum and end-diastolic pressure and relaxation time constant), paralleled by RV cardiomyocyte hypertrophy. Except for cardiomyocyte hypertrophy, aerobic exercise prevented these functional changes. Our data support that this model of HFpEF shows functional and structural changes in the RV that resemble the human HFpEF phenotype, reinforcing its utility to understand this pathophysiology and to adress novel therapeutic targets to manage HFpEF. In addition, we showed that aerobic exercise is cardioprotective for the RV. A deeper knowledge of the mechanisms underlying the benefits of aerobic exercise could also lead to the identification of therapeutic targets to be further explored.

© 2021 The Authors. Experimental Physiology © 2021 The Physiological Society.

Keywords

• aerobic exercise; HFpEF; right ventricle dysfunction; ZSF1 rats