Severe hypoxaemic hypercapnia compounds cerebral oxidative-nitrosative stress during extreme apnoea: Implications for cerebral bioenergetic function

We examined the extent to which apnoea-induced extremes of oxygen demand/carbondioxide production impact redox regulation of cerebral bioenergetic function. Ten ultra-eliteapnoeists (six men and four women) performed two maximal dry apnoeas preceded by normoxicnormoventilation, resulting in severe end-apnoea hypoxaemic hypercapnia, and hyperoxic hyper-ventilation designed to ablate hypoxaemia, resulting in hyperoxaemic hypercapnia. Transcerebralexchange of ascorbate radicals (by electron paramagnetic resonance spectroscopy) and nitric oxidemetabolites (by tri-iodide chemiluminescence) were calculated as the product of global cerebralblood flow (by duplex ultrasound) and radial arterial (a) to internal jugular venous (v) concentrationgradients. Apnoea duration increased from 306 +/- 62 s during hypoxaemic hypercapnia to 959 +/- 201 s in hyperoxaemic hypercapnia (P <= 0.001). Apnoea generally increased global cerebralblood flow (allP <= 0.001) but was insufficient to prevent a reduction in the cerebral metabolicrates of oxygen and glucose (P=0.015-0.044). This was associated with a general net cerebraloutput (v>a) of ascorbate radicals that was greater in hypoxaemic hypercapnia (P=0.046vs.hyperoxaemic hypercapnia) and coincided with a selective suppression in plasma nitrite uptake(a>v) and global cerebral blood flow (P=0.034 to<0.001vs. hyperoxaemic hypercapnia),implying reduced consumption and delivery of nitric oxide consistent with elevated cerebraloxidative-nitrosative stress. In contrast, we failed to observe equidirectional gradients consistentwithS-nitrosohaemoglobin consumption and plasmaS-nitrosothiol delivery during apnoea (allP >= 0.05). Collectively, these findings highlight a key catalytic role for hypoxaemic hypercapnia incerebral oxidative-nitrosative stress.