{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:33:19Z","timestamp":1790605999286,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003768","name":"Universit\u00e9 de Strasbourg","doi-asserted-by":"publisher","award":["ANR\u201010\u2010IDEX\u20100002\u201002"],"award-info":[{"award-number":["ANR\u201010\u2010IDEX\u20100002\u201002"]}],"id":[{"id":"10.13039\/501100003768","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>We aimed to evaluate an innovative dose\u2013response approach to assess the metaboreflex with control of intramuscular metabolic perturbation (concept of metaboreflex gain). We also investigated potential sex differences in the metaboreflex using this new approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Thirty participants (15 females) completed one familiarization and two experimental visits to evaluate the method and assess its reproducibility. Each visit involved four consecutive bouts of sustained isometric knee extension at 20% of maximal voluntary force interspersed with 2 min of post\u2010exercise circulatory occlusion (PECO). Intramuscular metabolic perturbation was quantified indirectly via changes in quadriceps twitch force evoked by electrical stimulation of the femoral nerve (\u2206Q\n                      <jats:sub>TW<\/jats:sub>\n                      ). Metaboreflex gain was calculated as the ratio of \u2206mean arterial pressure (\u2206MAP) during PECO to \u2206Q\n                      <jats:sub>TW<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found a gradual increase in \u2206MAP (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) that was linearly correlated with the gradual decrease in \u2206Q\n                      <jats:sub>TW<\/jats:sub>\n                      (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) during the exercise bouts (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.93;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.037). Bland\u2013Altman analysis showed a mean bias of 0.3\u2009\u00b1\u20090.5 for metaboreflex gain. Males exhibited greater metaboreflex to PECO than females when assessed \u201cclassically\u201d with no control of \u2206Q\n                      <jats:sub>TW<\/jats:sub>\n                      (\u2206MAP; 49.1%\u2009\u00b1\u200917.9% vs. 36.5%\u2009\u00b1\u20098.7%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.020), whereas there was no sex difference when assessed using the metaboreflex gain (\u2206MAP\/\u2206Q\n                      <jats:sub>TW<\/jats:sub>\n                      ; 1.3\u2009\u00b1\u20090.6 vs. 1.8\u2009\u00b1\u20091.3;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.325). The metaboreflex gain was not consistent across exercise bouts, showing that contrasting conclusions might emerge between two single assessments performed at different levels of metaboreflex activation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study highlights the critical need for using a dose\u2013response relationship while accounting for neuromuscular fatigue as a proxy for the metabolic stimulus when assessing the muscle metaboreflex in humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>Clinical trials registration number: NCT06775119<\/jats:p>\n                  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