Hypoxemia Destabilizes The Neurovascular Unit During Extreme Apnea In Humans

Abstract

To what extent voluntary asphyxia imposed by static apnea challenges the functional-structural limits of the neurovascular unit (NVU) in humans characterized by extremes of hypertension, hypoxemia and hypercapnia remains unclear. PURPOSE: To document the transcerebral exchange kinetics of NVU-specific proteins during extreme apnea and independent contributory influence of hypoxemia. METHODS: Ten world class breath-hold divers (6♂, 4♀) performed two maximal dry apneas preceded by normoxic normoventilation (NX: severe hypoxemia and hypercapnia) and hyperoxic hyperventilation (HX: absence of hypoxemia with exacerbating hypercapnia) with measurements obtained before and after apnea. Transcerebral exchange of NVU proteins (ELISA, Single Molecule Array) were calculated as the product of global cerebral blood flow (gCBF, duplex ultrasound) and radial arterial to internal jugular venous concentration gradients. RESULTS: Apnea duration increased from 5 m 6 s in NX to 15 m 59 s in HX (P = < 0.001) resulting in marked elevations in gCBF and venous S100B, glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase-L1 and total tau (all P < 0.05 vs. baseline). This culminated in net cerebral output reflecting increased blood-brain barrier permeability and neuro-glio-vascular dysfunction that was more pronounced in NX due to more severe systemic and intracranial hypertension (P < 0.05 vs. HX). CONCLUSION: These findings identify the hemodynamic stress to which the apneic brain is exposed, highlighting the critical contribution of hypoxemia and not just hypercapnia to NVU destabilization.