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

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. Knowledge about the RV functional and structural changes in HFpEF and the effect of aerobic exercise is still limited and desirable to expand. What is the main finding and its importance? The HFpEF ZSF1 rat model presents RV structural and functional changes, mimicking the human condition. We show that aerobic exercise prevented the decline in VO2 max, 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 knowledge emphasizes the importance of using exercise to manage HFpEF. Abstract Background : Right ventricular (RV) dysfunction is highly prevalent in HFpEF and is a marker of poor prognosis. We assessed the ZSF1 obese model of HFpEF to confirm if these rats also develop RV dysfunction and evaluated if aerobic exercise could prevent them. Methods and results ZSF1 obese rats were randomly allocated to aerobic exercise training group (n = 7; treadmill running, 5days/week, 60min/day, 15m/min, for 5 weeks) or to a sedentary group (n = 7). We also used ZSF1 lean rats (n = 7) as control group. After 5 weeks, rats were submitted to an exercise tolerance test, invasive hemodynamic evaluation, sacrificed and samples from RV were collected for histologic analysis. ZSF1 obese sedentary rats showed lower VO2 max, RV pressure-overload (e.g., higher mean and maximum systolic pressure) and diastolic dysfunction (e.g. higher minimal and end-diastolic pressurem and relaxation time constant), paralleled by RV cardiomyocyte hypertrophy. Except for cardiomyocyte hypertrophy, aerobic exercise prevented these functional changes.. Conclusions Our data supports that this model of HFpEF shows functional and structural changes in the RV that resemble the human HFpEF phenotype, reinforcing its utility to understand the pathophysiology and to adress novel therapeutic targets to manage HFpEF. In addition, we show 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. This article is protected by copyright. All rights reserved.