Inspiratory pressure support (IPS) plus positive end-expiratory pressure (PEEP) ventilation might potentially interfere with the "central" hemodynamic adjustments to exercise in patients with chronic obstructive pulmonary disease (COPD). Twenty-one non- or mildly-hypoxemic males (FEV(1) = 40.1 +/- 10.7% predicted) were randomly assigned to IPS (16 cmH(2)O) + PEEP (5 cmH(2)O) or spontaneous ventilation during constant-work rate (70-80% peak) exercise tests to the limit of tolerance (T (lim)). Heart rate (HR), stroke volume (SV), and cardiac output (CO) were monitored by transthoracic cardioimpedance (Physioflow, Manatec, France). Oxyhemoglobin saturation was assessed by pulse oximetry (SpO(2)). At similar SpO(2), IPS(16) + PEEP(5) was associated with heterogeneous cardiovascular effects compared with the control trial. Therefore, 11 patients (Group A) showed stable or increased Delta "isotime" - rest SV [5 (0-29) mL], lower DeltaHR but similar DeltaCO. On the other hand, DeltaSV [-10 (-15 to -3) mL] and DeltaHR were both lower with IPS(16) + PEEP(5) in Group B (N = 10), thereby reducing DeltaCO (p < 0.05). Group B showed higher resting lung volumes, and T (lim) improved with IPS(16) + PEEP(5) only in Group A [51 (-60 to 486) vs. 115 (-210 to 909) s, respectively; p < 0.05]. We conclude that IPS(16) + PEEP(5) may improve SV and exercise tolerance in selected patients with advanced COPD. Impaired SV and CO responses, associated with a lack of enhancement in exercise capacity, were found in a sub-group of patients who were particularly hyperinflated at rest.