Abstract: BACKGROUND: Clinical studies have shown that aerobic exercise is an important supplement to the clinical treatment of patients with pulmonary hypertension, which can alleviate the disease condition, increase exercise tolerance and improve the quality of life. However, it is not clear whether patients at different stages of pulmonary hypertension can benefit equally from exercise training. 
OBJECTIVE: To compare the intervention effects of early or late aerobic training on right heart failure in rats with pulmonary hypertension and explore its possible mechanism.
METHODS: Sixty male Wistar rats were randomly divided into control group, model sedentary group, model early exercise group and model late exercise group, with 15 rats in each group. The model of pulmonary hypertension was established by intraperitoneal injection of monocrotaline (60 mg/kg) in the latter three groups. The model early exercise group was given 8 weeks of treadmill aerobic exercise (60% maximum running speed, 60 minutes per day, 5 days a week) after modeling, while the model late exercise group was trained for 6 weeks after 2 weeks of modeling. The control and model sedentary groups were fed quietly in the rat cage for 8 weeks. After training, the exercise performance, right ventricular hemodynamics, cardiopulmonary function, cardiopulmonary histopathology, reactive oxygen species level in mitochondria, activity of mitochondrial respiratory chain complex and expressions of myocardial tissue proteins were detected. 
RESULTS AND CONCLUSION: Compared with the model sedentary group, exercise performance and right ventricular function improved (P < 0.05), myocardial collagen content, endothelin-1, tumor necrosis factor-α/interleukin-10 ratio and β-myosin heavy chain/α-myosin heavy chain ratio decreased (P < 0.05), vascular endothelial growth factor and sarcoplasmic reticulum calcium-adenosine triphosphate enzyme expression increased (P < 0.05), immunofluorescence intensity of mitochondrial reactive oxygen species and the protein expression of 3-nitrotyrosine decreased (P < 0.05), the activities of complex I, II, IV and V increased in the model early exercise and model late exercise groups (P < 0.05), but there were no significant changes in right ventricular maximum pressure, pulmonary acceleration time and pulmonary artery wall area/total vascular area ratio (P > 0.05). Compared with the model late exercise group, the model early exercise group further improved exercise performance and right ventricular function, and downregulated collagen content, brain natriuretic peptide protein expression, tumor necrosis factor-α/interleukin-10 ratio and β-myosin heavy chain/α-myosin heavy chain ratio (P < 0.05). To conclude, although pulmonary vascular remodeling and right ventricular overload persist in rats with pulmonary hypertension, exercise training at different stages of the disease has a cardioprotective effect. The mechanism is related to the improvement of cardiac remodeling, neurohormone system imbalance, inflammatory response and mitochondrial oxidative stress. Greater benefit is gained from initiating exercise in the early stage of the disease. 

Key words: pulmonary hypertension, aerobic exercise, cardiac remodeling, inflammation, oxidative stress, exercise performance, right heart failure