New Insights into the Influence of Tissue Desaturation on Skeletal Muscle Reactive Hyperemia: Implications for Sex-Related Differences

There is evidence showing that males have greater reactive hyperemia compared to females. However, females also show less desaturation rate and magnitude during blood flow occlusion compared to males, questioning whether the reduced reactive hyperemia observed in females is a consequence of reduced "ischemic" stimulus. We assessed femoral artery conduit artery and skeletal muscle (tibialis anterior) reactive hyperemia in 75 young healthy males (n = 38) and females (n = 37). Data was analyzed using different strategies such as: i) simple comparisons of indexes of reactive hyperemia of the full cohort without considering tissue desaturation; ii) indexes of reactive hyperemia comparisons between subjects that matched for tissue desaturation. iii) skeletal muscle reactive hyperemia comparisons between males and females from the full cohort by using other proposed methods in the literature; iv) comparison of skeletal muscle reactive hyperemia between males and females from the full cohort while controlling for desaturation indexes using analysis of covariance (ANCOVA). Overall, females showed reduced desaturation magnitude (20 ± 6% vs. 28 ± 5 %; p < 0.001) and near-infrared spectroscopy (NIRS)-derived reperfusion slope (Slope 2) (0.8 ± 0.2%.-1 vs. 1.4 ± 0.6%.-1; p < 0.001) compared to males. However, in a subset of tissue-desaturation matched participants, reactive hyperemia remained reduced in females compared to males (1.0 ± 0.2 vs. 1.3 ± 0.4; p = 0.018). When, tissue desaturation data were controlled by using ANCOVA, this approach was more accurate than other proposed normalizations for assessing skeletal muscle reactive hyperemia in males and females. our findings indicate that using proposed normalization models may neglect sex-related differences in reactive hyperemia. However, using ANCOVA to account for differences in desaturation may provide a more accurate approach when comparing skeletal muscle reactive hyperemia between males and females.