Continuous reduction in cerebral oxygenation during endurance exercise in patients with pulmonary arterial hypertension

Abstract

Background: Patients with pulmonary arterial hypertension (PAH) have lower cerebral blood flow (CBF) and oxygenation compared to healthy sedentary subjects, the latter negatively correlating with exercise capacity during incremental cycling exercise. We hypothesized that patients would also exhibit altered CBF and oxygenation during endurance exercise, which would correlate with endurance time.

Methods: Resting and exercise cardiorespiratory parameters, blood velocity in the middle cerebral artery (MCAv; transcranial doppler) and cerebral oxygenation (relative changes in cerebral tissue oxygenation index (ΔcTOI) and cerebral deoxyhemoglobin (ΔcHHb); near-infrared spectroscopy) were continuously monitored in nine PAH patients and 10 healthy-matched controls throughout endurance exercise. Cardiac output (CO), systemic blood pressure (BP) and oxygen saturation (SpO₂ ), ventilatory metrics and end-tidal CO₂ pressure (P_ET CO₂ ) were also assessed noninvasively.

Results: Despite a lower workload and endurance oxygen consumption, similar CO and systemic BP, ΔcTOI was lower in PAH patients compared to controls (p < .01 for interaction). As expected during exercise, patients were characterized by an altered MCAv response to exercise, a lower P_ET CO₂ and SpO₂ , as wells as a higher minute-ventilation/CO₂ production ratio ( ${\dot{V}}_E/\dot{V}{\text{CO}}_2$ ratio). An uncoupling between changes in MCAv and P_ET CO₂ during the cycling endurance exercise was also progressively apparent in PAH patients, but absent in healthy controls. Both cHHb and ΔcTOI correlated with ${\dot{V}}_E/\dot{V}{\text{CO}}_2$ ratio (r = 0.50 and r = -0.52; both p < .05 respectively), but not with endurance time.

Conclusion: PAH patients present an abnormal cerebrovascular profile during endurance exercise with a lower cerebral oxygenation that correlate with hyperventilation but not endurance exercise time. These findings complement the physiological characterization of the cerebral vascular responses to exercise in PAH patients.

Keywords: cerebral blood flow; cerebral oxygenation; cycling endurance test; exercise physiology; pulmonary arterial hypertension; pulmonary hypertension.