Systemic hypoxemia catalyzes cerebral oxidative-nitrosative stress during extreme apnea in humans: implications for cerebral bioenergetic function
Bibliographic record
Abstract
ABSTRACT BACKGROUND Voluntary 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 (O 2 ) demand and carbon dioxide (CO 2 ) production impact redox homeostasis and corresponding red blood cell (RBC)-mediated cerebral vasodilation. METHODS Ten 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 ·- , 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. RESULTS Apnea 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 PaO 2 and SaO 2 respectively in HHA and PaCO 2 peak of 68 mmHg in IHA. Apnea resulted in a more pronounced elevation in the net cerebral output (v>a) of A ·- 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 ( ) 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 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. CONCLUSIONS These findings highlight a key catalytic role for hypoxemia in cerebral OXNOS with reduction the more likely mechanism underlying endocrine NO vasoregulation with the capacity to transduce physiological O 2 -CO 2 gradients into graded vasodilation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".