Functional and Metabolic Adaptations of Blood Flow Restriction Exercise in Rats and Post-surgical Patients

Blood flow restriction exercise (BFR-E) has gained popularity as a therapy used to improve muscle mass and strength in various clinical populations. However, the systemic and intramuscular responses to BFR-E are widely unknown. Here, we describe the functional and metabolic responses to BFR-E in our novel in vivo method of BFR-E in rats. Implementation of the model revealed increase in muscle mass and maximal strength in rats exposed to chronic BFR-E. Systemic metabolites related to glycolysis and redox metabolism were altered following acute BFR-E and metabolites related to amino acids and the TCA cycle were altered following chronic BFR-E. Moreover, transcriptomic analysis revealed a muscle-specific metabolic response to chronic BFR-E that coincided with morphological adaptations. Given the broad application of BFR-E in the rehabilitative setting, we examined the acute, systemic response to BFR-E in post-surgical human subjects. Semi-targeted metabolomic analysis revealed no significant alterations in circulating metabolites following acute BFR-E in humans, mirroring findings in acutely exercised rats. Together, these results suggest that the benefits of BFR-E are not mediated by acute systemic metabolic perturbations but instead arise from tissue-specific adaptations that develop with repeated exposure, establishing a conserved, translational framework for mechanistic investigation.