PT - JOURNAL ARTICLE AU - Danny Christiansen AU - Kasper H. Eibye AU - Villads Rasmussen AU - Hans M. Voldbye AU - Martin Thomassen AU - Michael Nyberg AU - Thomas G.P. Gunnarsson AU - Casper Skovgaard AU - Mads S. Lindskrog AU - David J. Bishop AU - Morten Hostrup AU - Jens Bangsbo TI - Cycling with blood flow restriction improves performance and muscle K<sup>+</sup> handling and blunts the effect of antioxidant infusion in humans AID - 10.1101/375881 DP - 2018 Jan 01 TA - bioRxiv PG - 375881 4099 - http://biorxiv.org/content/early/2018/10/24/375881.short 4100 - http://biorxiv.org/content/early/2018/10/24/375881.full AB - We examined if blood flow restriction (BFR) would augment training-induced improvements in muscle K+ handling and performance during intense exercise in men, and if these adaptations would be associated with an effect of muscle antioxidant function on thigh K+ release and with fibre type-dependent modulation of Na+,K+-ATPase-isoform abundance and FXYD1 phosphorylation. Ten recreationally-active men (25 ± 4 y, 49.7 ± 5.3 mL∙kg-1∙min-1) performed 6 weeks of interval cycling, where one leg trained without (control; CON-leg) and the other leg with BFR (BFR-leg, pressure: 178 mmHg). Before and after training, catheters were inserted into the femoral artery and vein, and blood flow was assessed during single-leg knee-extensions at 25% (Ex1) and 90% of leg peak aerobic power (Ex2) with intravenous infusion of N-acetylcysteine (NAC) or saline (placebo), and a resting muscle biopsy was collected. After training, performance during exhaustive exercise increased to a greater extent in BFR-leg (23%) than in CON-leg (12%, p&lt;0.05), whereas thigh K+ release during Ex2 was attenuated in BFR-leg only (p&lt;0.05). Before training, NAC depressed K+ release during Ex1 (p&lt;0.05), but not during Ex2 (p&gt;0.05). After training, this effect was blunted in BFR-leg (p&lt;0.05), whilst the abundance of Na+,K+-ATPase-isoform α1 in type-II (51%), β1 in type-I (33%), and FXYD1 in type-I (108%) and type-II (60%) fibres was higher in BFR-leg (p&lt;0.05; vs. CON-leg). Thus, interval training with BFR elicits greater improvements in performance and reduces muscle net K+ release during intense exercise, which may be caused by elevated ROS scavenging and fibre type-dependent increases in Na+,K+-ATPase-isoform abundance.Key pointsHere, we provide evidence that reactive oxygen species (ROS) play a role in regulating K+ homeostasis in the untrained musculature of humans, as indicated by attenuated thigh K+ efflux during exercise with concomitant antioxidant infusion.We also demonstrate that interval training with blood flow restriction (BFR) augments improvements in performance and reduces K+ release from contracting muscles during intense exerciseThe effect of training with BFR on muscle K+ handling appears to be partly mediated by increasing the protection against ROS, since the effect of antioxidant infusion was blunted after training with restricted blood flow.Further, training with BFR resulted in higher abundance of Na+,K+-ATPase-isoform α1 in type-II (51%), β1 in type-I (33%), and FXYD1 in type-I (108%) and type-II (60%) muscle fibres. This suggests fibre type-specific adaptations in Na+,K+-ATPase-isoform content are also important for improvements in muscle K+ handling by training with BFR in humans.