{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:38:51Z","timestamp":1780447131153,"version":"3.54.1"},"reference-count":60,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T00:00:00Z","timestamp":1597881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>A fall in oxygen supply releases a remedial response that is otherwise prevented when the oxygen supply is sufficient; for example, the remedial function of HIF\u20101\u03b1 is released when oxygen levels fall.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Concept: the physiological responses initiated when oxygen supply is compromised operate in a fail\u2010safe manner. This concept is applied to two cases: the control of cerebral blood flow, and the detection of hypoxia by the carotid body.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The fail\u2010safe oxygen supply concept was tested with simple computer simulations to demonstrate its function and verify the ability to reproduce measured data.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The computer model reproduced published observations, suggesting that the fail\u2010safe concept can be considered as a principle that provides novel insight into the physiology of oxygen supply in these cases.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>An engineered fail\u2010safe system automatically prevents or mitigates the consequences of a system failure. This operational concept can be applied both to the delivery of oxygen to the brain during hypoxia and anaemia, and to the carotid body response to hypoxia and hypercapnia. I aimed to develop simple mathematical models of these fail\u2010safe processes and examine their ability to replicate experimental observations. The intent is to demonstrate the validity of applying the fail\u2010safe concept, not to reveal the details of the physiology involved. The model calculations are based on a single compartment of the relevant tissue in each case that is challenged with a decrease in oxygen supply. The model equation parameters were adjusted to reproduce experimental observations. The fail\u2010safe model of cerebral blood flow control yielded results similar in form to published experimental observations of the cerebral blood flow responses to hypoxia and anaemia. The fail\u2010safe model of carotid body glomus cell control of intracellular hydrogen ion concentration also yielded results similar in form to observations of carotid sinus nerve responses to hypoxia and hypercapnia. The ability of these simple models to simulate experimental observations demonstrates the applicability of the fail\u2010safe concept to oxygen delivery. I suggest that a fail\u2010safe view of oxygen delivery provides novel physiological insight.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp280301","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T21:05:11Z","timestamp":1596747911000},"page":"4859-4867","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Fail\u2010safe aspects of oxygen supply"],"prefix":"10.1113","volume":"598","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2270-7392","authenticated-orcid":false,"given":"James","family":"Duffin","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Department of Physiology University of Toronto  Toronto Ontario Canada"},{"name":"Thornhill Medical  Toronto Ontario 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