Simulated altitude is medicine: Intermittent exposure to hypobaric hypoxia and cold accelerates injured skeletal muscle recovery

Abstract

Muscle injuries are the leading cause of sports casualties. Because of its high plasticity, skeletal muscle can respond to different stimuli to maintain and improve functionality. Intermittent hypobaric hypoxia (IHH) improves muscle oxygen, delivery and utilisation. Hypobaria coexists with cold in the biosphere, opening the possibility to consider the combined use of both environmental factors to achieve beneficial physiological adjustments. We studied the effects of intermittent hypobaric hypoxia and cold exposure, separately and simultaneously, on muscle regeneration. Adult male rats were surgically injured in one gastrocnemius and randomly assigned to the following groups: 1) CTRL: passive recovery; 2) COLD: intermittently exposed to cold (4°C); 3) HYPO: submitted to IHH (4,500m); 4) COHY: exposed to intermittent simultaneous cold and hypoxia. Animals were subjected to these interventions for 4h/day for 9 or 21 days. COLD and COHY presented faster muscle regeneration than CTRL, evidenced after 9 days at histological (dMHC-positive and centrally nucleated fibres reduction) and functional levels after 21 days. HYPO showed a full recovery from injury (at histological and functional levels) after 9 days, while COLD and COHY needed more time to induce a total functional recovery. IHH can be postulated as an anti-fibrotic treatment since it reduces collagen I deposition. The increase in the pSer473Akt/total Akt ratio observed after 9 days in COLD, HYPO and COHY, together with the increase in the pThr172AMPK<span style="color:black">α/</span>total AMPK<span style="color:black">α</span> ratio observed in the gastrocnemius of HYPO, provide clues to the responsible molecular mechanisms involved in the improved muscle regeneration.