Cerebral, Muscle and Blood Oxygenation in Patients with Pulmonary Vascular Disease Whilst Breathing Normobaric Hypoxia vs. Normoxia Before and After Sildenafil: Data from a Randomised Controlled Trial

Background: In patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension (summarized as pulmonary vascular disease; PVD), it is unclear whether the brain is protected against acute hypoxia and whether acute pulmonary vascular dilatation by sildenafil would influence cerebral and muscle tissue oxygenation whilst breathing normoxia or hypoxia. Methods: Adult patients with PVD underwent right heart catheterization, while cerebral and muscular tissue oxygenation and tissue hemoglobin index were measured using near-infrared spectroscopy along with arterial and mixed-venous blood gases. Participants underwent a four-stage protocol in which they were blinded to breathing either normoxia (FiO2 0.21) or normobaric hypoxia (FiO2 0.15), both before and after a single oral dose of sildenafil (50 mg) according to a randomized, cross-over design. Results: In 22 PVD patients (9 women, age 54 ± 14 y) under hypoxia, mean cerebral tissue oxygenation decreased by -2% (95% CI -4 to 0%, p = 0.046), muscular tissue oxygenation by -1% (95% CI -3 to 0%, p = 0.011) and mean arterial partial pressure of oxygen by -2.3 kPa (95% CI -2.7 to -1.8 kPa, p < 0.0001). Sildenafil improved the cerebral tissue hemoglobin index under hypoxia compared to hypoxia without sildenafil by 0.12 (95% CI 0.00 to 0.23, p = 0.049), but not the muscular tissue hemoglobin index. Conclusions: In PVD patients, acute exposure to normobaric hypoxia leads to a reduction in arterial oxygenation as well as cerebral and muscular tissue oxygenation. Sildenafil improves cerebral blood flow but has no effect on arterial, cerebral or muscular oxygenation.