{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:25:40Z","timestamp":1791897940886,"version":"4.3.4"},"reference-count":53,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007437","name":"TrygFonden","doi-asserted-by":"publisher","award":["101390"],"award-info":[{"award-number":["101390"]}],"id":[{"id":"10.13039\/501100007437","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007437","name":"TrygFonden","doi-asserted-by":"publisher","award":["20045"],"award-info":[{"award-number":["20045"]}],"id":[{"id":"10.13039\/501100007437","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:sec>\n                    <jats:title>New Findings<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:bold>What is the topic of this review?<\/jats:bold>\n                          <\/jats:p>\n                          <jats:p>Lactate is considered an important substrate for mitochondria in the muscles, heart and brain during exercise and is the main gluconeogenetic precursor in the liver and kidneys. In this light, we review the (patho)physiology of lactate metabolism in sepsis and coronavirus disease 2019 (COVID\u201019).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:bold>What advances does it highlight?<\/jats:bold>\n                          <\/jats:p>\n                          <jats:p>Elevated blood lactate is strongly associated with mortality in septic patients. Lactate seems unrelated to tissue hypoxia but is likely to reflect mitochondrial dysfunction and high adrenergic stimulation. Patients with severe COVID\u201019 exhibit near\u2010normal blood lactate, indicating preserved mitochondrial function, despite a systemic hyperinflammatory state similar to sepsis.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>In critically ill patients, elevated plasma lactate is often interpreted as a sign of organ hypoperfusion and\/or tissue hypoxia. This view on lactate is likely to have been influenced by the pioneering exercise physiologists around 1920. August Krogh identified an oxygen deficit at the onset of exercise that was later related to an oxygen \u2018debt\u2019 and lactate accumulation by A.\u00a0V. Hill. Lactate is considered to be the main gluconeogenetic precursor in the liver and kidneys during submaximal exercise, but hepatic elimination is attenuated by splanchnic vasoconstriction during high\u2010intensity exercise, causing an exponential increase in blood lactate. With the development of stable isotope tracers, lactate has become established as an important energy source for muscle, brain and heart tissue, where it is used for mitochondrial respiration. Plasma lactate\u00a0&gt;\u00a04\u00a0mM is strongly associated with mortality in septic shock, with no direct link between lactate release and tissue hypoxia. Herein, we provide evidence for mitochondrial dysfunction and adrenergic stimulation as explanations for the sepsis\u2010induced hyperlactataemia. Despite profound hypoxaemia and intense work of breathing, patients with severe coronavirus disease 2019 (COVID\u201019) rarely exhibit hyperlactataemia\u00a0(&gt;\u00a02.5\u00a0mM), while presenting a systemic hyperinflammatory state much like sepsis. However, lactate dehydrogenase, which controls the formation of lactate, is markedly elevated in plasma and strongly associated with mortality in severe COVID\u201019. We briefly review the potential mechanisms of the lactate dehydrogenase elevation in COVID\u201019 and its relationship to lactate metabolism based on mechanisms established in contracting skeletal muscle and the acute respiratory distress syndrome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/ep089474","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T17:41:49Z","timestamp":1622482909000},"page":"665-673","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["The role of lactate in sepsis and COVID\u201019: Perspective from contracting skeletal muscle metabolism"],"prefix":"10.1113","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8140-2583","authenticated-orcid":false,"given":"Ulrik Winning","family":"Iepsen","sequence":"first","affiliation":[{"name":"Centre for Physical Activity Research Copenhagen University Hospital \u2013 Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Anaesthesia and Intensive Care Copenhagen University Hospital \u2013 Bispebjerg and Frederiksberg Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronni R.","family":"Plovsing","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology Copenhagen University Hospital \u2013 Hvidovre Hospital  Copenhagen Denmark"},{"name":"Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Tjelle","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology Copenhagen University Hospital \u2013 Hvidovre Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai Bang","family":"Foss","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology Copenhagen University Hospital \u2013 Hvidovre Hospital  Copenhagen Denmark"},{"name":"Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian S.","family":"Meyhoff","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Intensive Care Copenhagen University Hospital \u2013 Bispebjerg and Frederiksberg Hospital  Copenhagen Denmark"},{"name":"Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla K.","family":"Ryrs\u00f8","sequence":"additional","affiliation":[{"name":"Centre for Physical Activity Research Copenhagen University Hospital \u2013 Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronan M. 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