Post-exercise intramuscular O2 supply is tightly coupled with a higher proximal-to-distal ATP synthesis rate in human tibialis anterior

Abstract

KEY POINTS: The post-exercise recovery of phosphocreatine, a measure of the oxidative capacity of muscles, as assessed by 31 P MR spectroscopy, shows a striking increase from distal to proximal along the human tibialis anterior muscle. To investigate why this muscle exhibits a greater oxidative capacity proximally, we tested whether the spatial variation in phosphocreatine recovery rate is related to oxygen supply, muscle fibre type or type of exercise. We revealed that oxygen supply also increases from distal to proximal along the tibialis anterior, and that it strongly correlated with phosphocreatine recovery. Carnosine level, a surrogate measure for muscle fibre type was not different between proximal and distal, and type of exercise did not affect the gradient in phosphocreatine recovery rate. Taken together, the findings of this study suggest that the post-exercise spatial gradients in oxygen supply and phosphocreatine recovery are driven by a higher intrinsic mitochondrial oxidative capacity proximally. ABSTRACT: Phosphorus magnetic resonance spectroscopy ( 31 P MRS) of human tibialis anterior (TA) revealed a strong proximo-distal gradient in the post-exercise phosphocreatine (PCr) recovery rate constant (k PCr ), a measure of muscle oxidative capacity. The aim of this study was to investigate whether this k PCr gradient is related to O 2 supply, resting phosphorylation potential, muscle fibre type, or type of exercise. Fifteen male volunteers performed continuous isometric ankle dorsiflexion at 30% maximum force until exhaustion. At multiple locations along the TA, we measured the oxidative PCr resynthesis rate (V PCr = k PCr × PCr depletion) by 31 P MRS, the oxyhaemoglobin recovery rate constant (k O2Hb ) by near infrared spectroscopy, and muscle perfusion with MR intravoxel incoherent motion imaging. The k O2Hb , k PCr , V PCr and muscle perfusion depended on measurement location (P < 0.001, P < 0.001, P = 0.032 and P = 0.003, respectively), all being greater proximally. The k O2Hb and muscle perfusion correlated with k PCr (r = 0.956 and r = 0.852, respectively) and V PCr (r = 0.932 and r = 0.985, respectively), the latter reflecting metabolic O 2 consumption. Resting phosphorylation potential (PCr/inorganic phosphate) was also higher proximally (P < 0.001). The surrogate for fibre type, carnosine content measured by 1 H MRS, did not differ between distal and proximal TA (P = 0.884). Performing intermittent exercise to avoid exercise ischaemia, still led to larger k PCr proximally than distally (P = 0.013). In conclusion, the spatial k PCr gradient is strongly associated with the spatial variation in O 2 supply. It cannot be explained by exercise-induced ischaemia nor by fibre type. Our findings suggest it is driven by a higher proximal intrinsic mitochondrial oxidative capacity, apparently to support contractile performance of the TA.