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Linear mixed\u2010effects models were used to analyze the relationships between peak twitch force and intramuscular hydrogen ion or inorganic phosphate concentration (as <jats:italic>Z<\/jats:italic>\u2010scores) during the protocols that decreased peak twitch force (2\u2010 and 4\u2010Hz).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Although intramuscular hydrogen ion and inorganic phosphate concentrations increased with increasing frequencies of contraction, peak twitch force did not begin to decrease until a \u201cthreshold\u201d inorganic phosphate concentration was reached. A given hydrogen ion accumulation was associated with a greater decrease in peak twitch force during 4\u2010Hz compared to 2\u2010Hz (<jats:italic>\u03b2<\/jats:italic>: \u22121.19 vs. \u22120.62, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). In contrast, the decrease in peak twitch force for a given inorganic phosphate accumulation was not different between 4\u2010 and 2\u2010Hz (<jats:italic>\u03b2<\/jats:italic>: \u22120.89 vs. \u22120.85, <jats:italic>p<\/jats:italic>\u2009=\u20090.889).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The inconsistent relationship between the decrease in twitch force and intramuscular hydrogen ion accumulation is not congruent with the primary mechanisms by which acidosis is thought to mediate muscle fatigue. In contrast, the discernible twitch force\u2013inorganic phosphate breakpoint and the consistent relationship between the decrease in twitch force and intramuscular inorganic phosphate accumulation are congruent with the concept of a critical concentration beyond which inorganic phosphate mediates muscle fatigue.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.70083","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T10:40:52Z","timestamp":1753094452000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Skeletal Muscle Fatigue in Rats Is More Consistently Related to Increased Inorganic Phosphate Concentration Than Acidosis"],"prefix":"10.1111","volume":"241","author":[{"given":"Matthew T.","family":"Lewis","sequence":"first","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine University of Utah  Salt Lake City Utah USA"},{"name":"Geriatric Research, Education, and Clinical Center Veterans Affairs Medical Center  Salt Lake City Utah USA"},{"name":"Department of Physiology Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4767-7249","authenticated-orcid":false,"given":"Fabio G.","family":"Laginestra","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse C.","family":"Craig","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine University of Utah  Salt Lake City Utah USA"},{"name":"Geriatric Research, Education, and Clinical Center Veterans Affairs Medical Center  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Amann","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine University of Utah  Salt Lake City Utah USA"},{"name":"Geriatric Research, Education, and Clinical Center Veterans Affairs Medical Center  Salt Lake City Utah USA"},{"name":"Department of Anesthesiology University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell S.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine University of Utah  Salt Lake City Utah USA"},{"name":"Geriatric Research, Education, and Clinical Center Veterans Affairs Medical Center  Salt Lake City Utah USA"},{"name":"Department of Nutrition and Integrative Physiology University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Wiseman","sequence":"additional","affiliation":[{"name":"Department of Physiology Michigan State University  East Lansing Michigan USA"},{"name":"Department of Radiology Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7388-2214","authenticated-orcid":false,"given":"Ryan M.","family":"Broxterman","sequence":"additional","affiliation":[{"name":"Division of Geriatrics, Department of Internal Medicine University of Utah  Salt Lake City Utah USA"},{"name":"Geriatric Research, Education, and Clinical Center Veterans Affairs Medical Center  Salt Lake City Utah 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