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 (SpO ₂), ventilatory metrics and end‐tidal CO ₂ pressure (P _ETCO ₂) 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 _ETCO ₂ and SpO ₂, as wells as a higher minute‐ventilation/CO ₂ production ratio ( ${\dot{V}}_{\mathrm{E}}/\dot{V}{\text{CO}}_2$ ratio). An uncoupling between changes in MCAv and P _ETCO ₂ during the cycling endurance exercise was also progressively apparent in PAH patients, but absent in healthy controls. Both cHHb and ΔcTOI correlated with ${\dot{V}}_{\mathrm{E}}/\dot{V}{\text{CO}}_2$ 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.

Abstract

The novel findings of this study are that abnormal cerebrovascular responses to exercise are present during an endurance exercise protocol in patients with pulmonary arterial hypertension. It includes a reduction in cerebral oxygenation associated with higher minute‐ventilation/carbon dioxide production rather than endurance time, and an uncoupling between changes in mean blood velocity in the middle cerebral artery and end‐tidal carbon dioxide partial pressure during exercise in patients only. These findings add to the existing literature reporting abnormalities in cerebral blood flow determinants in pulmonary arterial hypertension.