BACKGROUND: Pulmonary VO2 on-kinetics during light-to-moderate-intensity constant-work-rate exercise, an experimental model mirroring energetic transitions during daily activities, has been shown to speed up with aerobic exercise training (AET) in normal subjects, but scant data are available in chronic heart failure (CHF). METHODS AND RESULTS: Thirty CHF patients were randomized to 3 months of light-to-moderate-intensity AET (CHF-AET) or control (CHF-C). Baseline and end-protocol evaluations included (i) one incremental cardiopulmonary exercise test with near infrared spectroscopy analysis of peak deoxygenated hemoglobin+myoglobin concentration changes (deoxy(Hb+Mb)) in vastus lateralis muscle, (ii) 8 light-to-moderate-intensity constant-work-rate exercise tests for VO2 on-kinetics phase I duration, phase II, and mean response time (MRT) assessment, and (iii) circulating endothelial progenitor cell (EPC) measurement. Reference values were obtained in 7 age-matched normals (N). At end-protocol, phase I duration, phase II, and MRT were significantly reduced (-12%, -22%, and -19%, respectively) and peak VO2, peak deoxy(Hb+Mb), and EPCs increased (9%, 20%, and 98%, respectively) in CHF-AET, but not in CHF-C. Peak deoxy(Hb+Mb) and EPCs relative increase correlated significantly to that of peak VO2 (r = 0.61 and 0.64, respectively, p < 0.05). CONCLUSIONS: Light-to-moderate-intensity AET determined a near-normalization of pulmonary VO2 on-kinetics in CHF patients. Such a marked plasticity has important implications for AET intensity prescription, especially in patients more functionally limited and with high exercise-related risk. The AET-induced simultaneous improvement of phase I and phase II, associated with an increase of peak peripheral oxygen extraction and EPCs, supports microcirculatory O2 delivery impairment as a key factor determining exercise intolerance in CHF.

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