Greater intramuscular metabolic perturbations contribute to faster muscle fatigue development in males than females during intermittent isometric exercise
Authors: Colosio Marta , Lamboglia Matteo , Pastorio Elisa , Gatti Marco , Vernillo Gianluca , Temesi John , Fiorenza Matteo 
Published: May 2024

INTRODUCTION: Previous studies reported faster performance fatigability in males than females during isometric exercise, ultimately prolonging time to task failure in the latter at the same relative intensity. Several authors suggested anatomical and physiological factors as primary determinants, but it remains unknown whether exercise-related accumulation of metabolites within skeletal muscle differentially affects fatigue development in female and males. PURPOSE: This study aimed to investigate intramuscular metabolic perturbations during fatiguing intermittent isometric knee-extensor exercise in males and females. Herein, we tested the hypothesis that greater metabolic perturbation during intermittent isometric exercise results in greater fatigue development in males compared to females. Methods: Fifteen males (M)(26±2y) and fifteen eumenorrheic females (F)(24±3y) visited the laboratory twice. During visit 1, isometric knee-extensors critical torque (CT) was estimated by a 5-min all-out test. In visit 2, participants performed intermittent isometric knee-extensor exercises to task failure at 110% of CT. To determine knee-extensors magnitude and etiology of fatigue maximal voluntary isometric contraction (MVIC), voluntary activation (VA) and potentiated twitches (St) amplitudes were evaluated before (PRE), at 9min (MID), and at task failure (POST). At the same time points, intramuscular pH and concentrations of ATP, PCr, Cr and La were determined in vastus lateralis muscle biopsies. Results: Time to task failure was shorter in M than F (1017±498 vs 1511±506s; P<.01). At PRE, MVIC torque was higher in M than F (259±70 vs 152±24Nm; P<.001). Relative decline in MVIC torque from PRE to MID was greater in M than F (-43±9 vs -34±8% from PRE; P<.05) but reached similar decline at POST (-55±7 vs -53±6% from PRE). VA decreased throughout the test similarly in both sexes (P<.001). St loss from PRE was higher in M than F (-45±13 vs -37±15%; P<.05) at MID whereas no sex differences were observed at POST. Muscle pH decreased at a similar rate in M and F during the test (P<.03). Muscle [ATP] did not change from PRE to MID or POST. Muscle [Cr] increased at a similar rate in M and F during the test (P<.01). Muscle [PCr] was lower in M than F at any time point (P<.03). At MID, [La] increased to a greater extent in M than F (P<.01) with no between-sex differences at POST. CONCLUSION: Males showed greater fatigue development than females associated with greater metabolic perturbation during intermittent isometric exercise performed at same relative intensity. Higher PCr depletion and higher La accumulation suggest females were less fatigable than males due to higher glycolytic rate and less intramuscular inorganic phosphate concentration. The present work was funded by a Travelling Fellowship grant JEBTF2210859 to MC from The Company Of Biologists Limited. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.