Cerebral microvascular blood flow and CO2 reactivity in pulmonary arterial hypertension

• Microvascular cerebral blood flow (CBFmicr) was lower in PAH patients than healthy controls.
• CBFmicr increased less from hypo to hypercapnia in patients thereby indicating impaired reactivity to CO2.
• These abnormalities might be associated with negative clinical outcomes and amenable to pharmacological treatment in PAH.

Hypocapnia and endothelial dysfunction might impair microvascular cerebral blood flow (CBFmicr) and cerebrovascular reactivity to CO2 (CVRCO2). Pulmonary arterial hypertension (PAH) is characteristically associated with chronic alveolar hyperventilation and microvascular endothelial dysfunction. We therefore determined CBFmicr (pre-frontal blood flow index (BFI) by the indocyanine green-near infrared spectroscopy methodology) during hypocapnia and hypercapnia in 25 PAH patients and 10 gender- and age-matched controls. Cerebral BFI was lower in patients than controls at similar transcutaneous PCO2 (PtcCO2) levels in both testing conditions. In fact, while BFI increased from hypocapnia to hypercapnia in all controls, it failed to increase in 17/25 (68%) patients. Thus, BFI increased to a lesser extent from hypo to hypercapnia (“Δ”) in patients, i.e., they showed lower Δ BFI/Δ PtcCO2 ratios than controls. In conclusion, CBFmicr and CVRCO2 are lessened in clinically stable, mildly-impaired patients with PAH. These abnormalities might be associated with relevant clinical outcomes (hyperventilation and dyspnea, cognition, cerebrovascular disease) being potentially amenable to pharmacological treatment.