Chapter 2. The Oxygen Paradox: Why CO₂ Must Always Lead the Way

Oxygen as Essential but Potentially Harmful in Excess

Thomas, A., et al. (2022). Oxygen supplementation and hyperoxia in critically ill patients. Frontiers in Medicine.
https://www.frontiersin.org/articles/10.3389/fmed.2022.865354/full

Semler, M. W., et al. (2022). Oxygen saturation targets for critically ill adults receiving mechanical ventilation. New England Journal of Medicine.
https://www.nejm.org/doi/full/10.1056/NEJMoa2203297

Xu, F., et al. (2012). Effect of hypoxia and hyperoxia on cerebral blood flow, blood oxygenation, and oxidative metabolism. Journal of Cerebral Blood Flow and Metabolism.
https://journals.sagepub.com/doi/10.1038/jcbfm.2012.93

Heyboer, M., et al. (2017). Hyperbaric oxygen therapy: side effects defined and quantified. Undersea and Hyperbaric Medicine.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467109/

Sadri, R. A., et al. (2022). Hyperbaric oxygen therapy complications. StatPearls.
https://www.ncbi.nlm.nih.gov/books/NBK470454/

Oxygen, Oxidative Stress, and the “Fuel and Fire” Concept

Lane, N. (2002). Oxygen: The Molecule That Made the World. Oxford University Press.
https://global.oup.com/academic/product/oxygen-9780198607839

Zhu, H., et al. (2016). Oxygen and oxygen toxicity: the birth of concepts. Annals of Translational Medicine.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070806/

Carter, R. (2003). Oxygen toxicity and ageing. British Medical Journal review.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1126548/

Why the Body Does Not Store Oxygen but Does Store Carbon Dioxide

Magor Elliott, S. R. M., et al. (2021). Dynamic modeling of body oxygen and carbon dioxide stores. American Journal of Physiology.
https://journals.physiology.org/doi/10.1152/ajpregu.00202.2020

WFSA Education Committee. Carbon dioxide transport and acid–base physiology.
https://resources.wfsahq.org/wp-content/uploads/CO2_transport.pdf

Ganong, W. F. Review of Medical Physiology. McGraw Hill. Carbon dioxide transport chapter.
https://accessmedicine.mhmedical.com

Hyperventilation, Hypocapnia, and Respiratory Alkalosis

Sharma, S., et al. (2023). Hypocarbia. StatPearls.
https://www.ncbi.nlm.nih.gov/books/NBK493197/

Cleveland Clinic. Hyperventilation syndrome.
https://my.clevelandclinic.org/health/diseases/17752-hyperventilation-syndrome

Medscape. Respiratory alkalosis.
https://emedicine.medscape.com/article/301680-overview

The Bohr Effect and CO₂ as the Signal for Oxygen Release

Bohr, C., Hasselbalch, K., and Krogh, A. (1904). Influence of carbon dioxide on oxygen binding of blood.
English translation hosted by University of Delaware.
https://udel.edu/~jrandall/Bohr1904.pdf 

Benner, A., et al. (2022). Physiology, Bohr effect. StatPearls.
https://www.ncbi.nlm.nih.gov/books/NBK482388/

West, J. B. (2019). Three classical papers in respiratory physiology by Christian Bohr. American Journal of Physiology.
https://journals.physiology.org/doi/full/10.1152/ajplung.00103.2019

Hyperoxia, Vasoconstriction, and Reduced Oxygen Utilization

Danger, A., et al. (2007). Hyperoxia induced tissue hypoxia.
https://pubmed.ncbi.nlm.nih.gov/17304245/

Thomas, A., et al. (2022). Oxygen supplementation and hyperoxia in critically ill patients.
https://www.frontiersin.org/articles/10.3389/fmed.2022.865354/full

Carbogen and Dual Gas Therapy

Sedlacik, J., et al. (2008). Influence of carbon dioxide on cerebral blood flow using carbogen. NeuroImage.
https://www.sciencedirect.com/science/article/pii/S1053811908002670

Ashkanian, M., et al. (2009). Carbogen inhalation improves oxygen delivery in hypoperfused brain tissue. Brain Research.
https://pubmed.ncbi.nlm.nih.gov/19100725/

Stubbs, M., et al. (1998). Effects of carbogen breathing on tumor physiology. British Journal of Cancer.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2062902/

Historical Foundations: Priestley and Lavoisier

American Chemical Society. Joseph Priestley and the discovery of oxygen.
https://www.acs.org/education/whatischemistry/landmarks/priestleyoxygen.html

American Chemical Society. Antoine Lavoisier and the chemical revolution.
https://www.acs.org/education/whatischemistry/landmarks/lavoisier.html

West, J. B. (2013). Lavoisier and the chemical revolution. American Journal of Physiology.
https://journals.physiology.org/doi/full/10.1152/ajplung.00190.2013

Environmental Context of CO₂ as a “Global Threat”

IPCC Third Assessment Report. The carbon cycle and atmospheric carbon dioxide.
https://www.ipcc.ch/report/ar3/wg1/

Optional Further Reading for General Readers

Lane, N. Oxygen: The Molecule That Made the World.
https://global.oup.com/academic/product/oxygen-9780198607839

West, J. B. Respiratory Physiology: The Essentials.
https://shop.lww.com/Respiratory-Physiology/p/9781975159049

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