Systemic hypoxemia catalyzes cerebral oxidative-nitrosative stress during extreme apnea in humans: implications for cerebral bioenergetic function

BACKGROUNDVoluntary asphyxia induced by apnea in competitive breath hold (BH) divers affords a unique opportunity to examine integrated mechanisms underlying the preservation of cerebral bioenergetic function. This study examined to what extent physiological extremes of oxygen (O2) demand and carbon dioxide (CO2) production impact redox homeostasis and corresponding red blood cell (RBC)-mediated cerebral vasodilation. METHODSTen ultra-elite apneists (6 men, 4 women) aged 33 {+/-} 9 (mean {+/-} SD) years old performed two maximal dry apneas preceded by, [1] normoxic normoventilation resulting in severe hypoxemic hypercapnia apnea (HHA) and [2] hyperoxic hyperventilation designed to prevent hypoxemia resulting in isolated hypercapnic apnea (IHA). Transcerebral exchange kinetics of ascorbate radicals (A{middle dot}-, electron paramagnetic resonance spectroscopy), lipid hydroperoxides (LOOH, spectrophotometry) and nitric oxide metabolites (NO, tri-iodide reductive chemiluminescence) were calculated as the product of global cerebral blood flow (gCBF, duplex ultrasound) and radial arterial (a) to internal jugular venous (v) concentration gradients determined at eupnea and after apnea. RESULTSApnea duration increased from 306 {+/-} 62 s during HHA to 959 {+/-} 201 s during IHA (P = <0.001), resulting in individual nadirs of 29 mmHg and 40 % for PaO2 and SaO2 respectively in HHA and PaCO2 peak of 68 mmHg in IHA. Apnea resulted in a more pronounced elevation in the net cerebral output (v>a) of A{middle dot}- and LOOH in HHA (P = <0.05 vs. IHA). This coincided with a lower apnea-induced increase in gCBF (P = <0.001 vs. IHA) and related suppression in plasma nitrite ([Formula]) uptake (a>v) (P = < 0.05 vs. IHA), implying reduced consumption and delivery of NO consistent with elevated cerebral oxidative-nitrosative stress (OXNOS). While apnea-induced gradients consistently reflected plasma [Formula] consumption (a>v) and RBC iron nitrosylhemoglobin formation (v>a), we failed to observe equidirectional gradients consistent with S-nitrosohemoglobin consumption and plasma S-nitrosothiol delivery. CONCLUSIONSThese findings highlight a key catalytic role for hypoxemia in cerebral OXNOS with [Formula] reduction the more likely mechanism underlying endocrine NO vasoregulation with the capacity to transduce physiological O2-CO2 gradients into graded vasodilation.