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Leg extension exercise increases the quadriceps muscles\u2019 blood flow 100-times; transporting 17 sextillion O2 molecules per kilogram per minute from microcirculation (capillaries) to mitochondria powering their cellular energetics. Within these muscles, the capillary network constitutes a prodigious blood-tissue interface essential to exchange O2 and carbon dioxide requisite for muscle function. In disease, microcirculatory dysfunction underlies the pathophysiology of heart failure, diabetes, hypertension, pulmonary disease, sepsis, stroke and senile dementia. Effective therapeutic countermeasure design demands knowledge of microvascular\/capillary function in health to recognize and combat pathological dysfunction. Dated concepts of skeletal muscle capillary (from the Latin capillus meaning \u2018hair\u2019) function prevail despite rigorous data-supported contemporary models; hindering progress in the field for future and current students, researchers and clinicians. Following closely the 100th anniversary of August Krogh\u2019s 1920 Nobel Prize for capillary function this Evidence Review presents an anatomical and physiological development of this dynamic field: Constructing a scientifically defensible platform for our current understanding of microcirculatory physiological function in supporting blood-mitochondrial O2 transport. New developments include: 1. Putative roles of red blood cell aquaporin and rhesus channels in determining tissue O2 diffusion. 2. Recent discoveries regarding intramyocyte O2 transport. 3. Developing a comprehensive capillary functional model for muscle O2 delivery-to-V\u0307O2 matching. 4. Use of kinetics analysis to discriminate control mechanisms from collateral or pathological phenomena.<\/jats:p>","DOI":"10.1093\/function\/zqad013","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T21:26:25Z","timestamp":1679001985000},"source":"Crossref","is-referenced-by-count":53,"title":["Capillary-Mitochondrial Oxygen Transport in Muscle: Paradigm Shifts"],"prefix":"10.1152","volume":"4","author":[{"given":"David C","family":"Poole","sequence":"first","affiliation":[{"name":"Departments of Kinesiology, Anatomy and Physiology, College of Veterinary Medicine, Kansas State University , Manhattan Kansas 66506 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy I","family":"Musch","sequence":"additional","affiliation":[{"name":"Departments of Kinesiology, Anatomy and Physiology, College of Veterinary Medicine, Kansas State University , Manhattan Kansas 66506 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","published-online":{"date-parts":[[2023,3,16]]},"reference":[{"issue":"2","key":"2023050809343894300_bib1","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/cphy.c100072","article-title":"Oxygen uptake kinetics","volume":"2","author":"Poole","year":"2012","journal-title":"Compr Physiol"},{"issue":"1","key":"2023050809343894300_bib2","first-page":"203","article-title":"Exercise: kinetic considerations for gas exchange","volume":"1","author":"Rossiter","year":"2011","journal-title":"Compr Physiol"},{"issue":"4","key":"2023050809343894300_bib3","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1113\/expphysiol.2009.050500","article-title":"Influence of hyperoxia on muscle metabolic responses and the power-duration relationship during severe-intensity exercise in humans: a 31P magnetic resonance spectroscopy study","volume":"95","author":"Vanhatalo","year":"2010","journal-title":"Exp Physiol"},{"issue":"2","key":"2023050809343894300_bib4","first-page":"113","article-title":"Influence of hypoxia on the power-duration relationship during high-intensity exercise","volume":"36","author":"Simpson","year":"2015","journal-title":"Int J Sports Med"},{"key":"2023050809343894300_bib5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.resp.2017.12.002","article-title":"Effects of normobaric hypoxia on upper body critical power and anaerobic working capacity","volume":"249","author":"La\u00a0Monica","year":"2018","journal-title":"Respir Physiol Neurobiol"},{"issue":"5","key":"2023050809343894300_bib6","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1249\/MSS.0000000000002234","article-title":"Effect of hyperoxia on critical power and V\u0307O2 kinetics during upright cycling","volume":"52","author":"Goulding","year":"2020","journal-title":"Med Sci Sports Exerc"},{"issue":"9","key":"2023050809343894300_bib7","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1080\/00140138808966766","article-title":"Metabolic and respiratory profile of the upper limit for prolonged exercise in man","volume":"31","author":"Poole","year":"1988","journal-title":"Ergonomics"},{"issue":"10","key":"2023050809343894300_bib8","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1249\/MSS.0b013e3181d9cf7f","article-title":"Critical power: implications for determination of V\u02d9O2 max and exercise tolerance","volume":"42","author":"Jones","year":"2010","journal-title":"Med Sci Sports Exerc"},{"issue":"3","key":"2023050809343894300_bib9","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1249\/00005768-198203000-00005","article-title":"Blood doping and related issues: a brief review","volume":"14","author":"Gledhill","year":"1982","journal-title":"Med Sci Sports Exerc"},{"issue":"6","key":"2023050809343894300_bib10","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1152\/jappl.1993.75.6.2586","article-title":"Effects of hyperoxia on maximal leg O2 supply and utilization in men","volume":"75","author":"Knight","year":"1993","journal-title":"J Appl Physiol (1985)"},{"issue":"3","key":"2023050809343894300_bib11","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1042\/CS20000104","article-title":"Insulin stimulates laser Doppler signal by rat muscle in vivo, consistent with nutritive flow recruitment","volume":"100","author":"Clark","year":"2001","journal-title":"Clin Sci (Lond)"},{"issue":"6","key":"2023050809343894300_bib12","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1055\/s-2007-971935","article-title":"Vascular control of nutrient delivery by flow redistribution within muscle: implications for exercise and post-exercise muscle metabolism","volume":"19","author":"Clark","year":"1998","journal-title":"Int J Sports Med"},{"key":"2023050809343894300_bib13","first-page":"841","article-title":"Cellular processes integrating the metabolic response to exercise","volume-title":"Handbook of Physiology. 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