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The Earth's 24-h planetary rotation, with predictable light and heat cycles, has driven profound evolutionary adaptation, with prominent impacts on physiological mechanisms important for surviving critical illness. Pathways of interest include inflammation, mitochondrial function, energy metabolism, hypoxic signaling, apoptosis, and defenses against reactive oxygen species. Regulation of these by the cellular circadian clock (BMAL-1 and its network) has an important influence on pulmonary inflammation; ventilator-associated lung injury; septic shock; brain injury, including vasospasm; and overall mortality in both animals and humans. Whether it is cytokines, the inflammasome, or mitochondrial biogenesis, circadian medicine represents exciting opportunities for translational therapy in intensive care, which is currently lacking. Circadian medicine also represents a link to metabolic determinants of outcome, such as diabetes and cardiovascular disease. More than ever, we are appreciating the problem of circadian desynchrony in intensive care. This review explores the rationale and evidence for the importance of the circadian clock in surviving critical illness.

Original publication

DOI

10.1177/07487304221092727

Type

Journal article

Journal

J Biol Rhythms

Publication Date

08/2022

Volume

37

Pages

385 - 402

Keywords

acute kidney injury, acute respiratory distress syndrome, brain injury, chronotherapy, circadian, critical care, critical illness, cytokines, epigenetic, immunomodulation, inflammasome, inflammation, intensive care, mitochondria, multiorgan failure, therapy, ventilator-associated lung injury, Animals, Circadian Clocks, Circadian Rhythm, Critical Care, Critical Illness, Humans, Inflammation, Mitochondria, Muscles