Cerebral microvascular blood flow and CO₂ reactivity in pulmonary arterial hypertension

Hypocapnia and endothelial dysfunction might impair microvascular cerebral blood flow (CBF_micr) and cerebrovascular reactivity to CO₂ (CVR_CO2). Pulmonary arterial hypertension (PAH) is characteristically associated with chronic alveolar hyperventilation and microvascular endothelial dysfunction. We therefore determined CBF_micr (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, CBF_micr and CVR_CO2 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.