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 31P 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 (31P MRS) of human tibialis anterior (TA) revealed a strong proximo‐distal gradient in the post‐exercise phosphocreatine (PCr) recovery rate constant (kPCr), a measure of muscle oxidative capacity. The aim of this study was to investigate whether this kPCr gradient is related to O2 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 (VPCr = kPCr × PCr depletion) by 31P MRS, the oxyhaemoglobin recovery rate constant (kO2Hb) by near infrared spectroscopy, and muscle perfusion with MR intravoxel incoherent motion imaging. The kO2Hb, kPCr, VPCr 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 kO2Hb and muscle perfusion correlated with kPCr (r = 0.956 and r = 0.852, respectively) and VPCr (r = 0.932 and r = 0.985, respectively), the latter reflecting metabolic O2 consumption. Resting phosphorylation potential (PCr/inorganic phosphate) was also higher proximally (P < 0.001). The surrogate for fibre type, carnosine content measured by 1H MRS, did not differ between distal and proximal TA (P = 0.884). Performing intermittent exercise to avoid exercise ischaemia, still led to larger kPCr proximally than distally (P = 0.013). In conclusion, the spatial kPCr gradient is strongly associated with the spatial variation in O2 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.

Microvascular response to exercise varies along the length of the tibialis anterior muscle

“…Moreover, the significant interaction effects between time postexercise and slice location indicate a faster microvascular response to exercise in the proximal slice, reflected by faster MBF recovery, an earlier peak in T 2 *, and a lower ATT (i.e., shorter arrival times) during the first 2 min postexercise. The difference in muscle perfusion and microvascular response to exercise between two separated slices along the proximodistal axis is in line with data in the literature assessing oxidative capacity in muscle 7,8,11 . The specific delayed response in T 2 * in the distal slice is in line with the findings reported by Boss et al 7 The reason for the proximodistal differences is still under debate.…”

“…The difference in muscle perfusion and microvascular response to exercise between two separated slices along the proximodistal axis is in line with data in the literature assessing oxidative capacity in muscle. 7,8,11 The specific delayed response in T 2 * in the distal slice is in line with the findings reported by Boss et al 7 The reason for the proximodistal differences is still under debate. One possible reason could be that the number of oxidative fibers increases from the distal to the proximal end, as was found in rodents.…”

“…The proximodistal differences found in previous papers are in general more pronounced than those found in the current study, although a direct comparison is difficult due to distinct study designs and readouts 7,8,11 . The relatively large differences found by Heskamp et al 8 and Boss et al 7 can be explained by a larger coverage (180 vs. 70 mm).…”

“…The proximodistal differences found in previous papers are in general more pronounced than those found in the current study, although a direct comparison is difficult due to distinct study designs and readouts. 7,8,11 The relatively large differences found by Heskamp et al 8 and Boss et al 7 can be explained by a larger coverage (180 vs. 70 mm). Heskamp et al 8 only found differences in blood flow-related parameters between the most distal and most proximal slice and Boss et al 7 also found the largest differences between the outer slices.…”

“…Most studies using ASL in muscle have only reported data from a single slice with the implicit assumption that muscle perfusion is homogeneous. 1,[3][4][5][6] Recent literature, however, has reported proximodistal differences in perfusion-related parameters and oxidative capacity, measured by IVIM, T 2 *, and 31 P MRS. 7,8 Proximodistal differences could be relevant for pathological situations, such as diabetes and peripheral artery disease, 9,10 because it can be argued that muscle regions with inherently lower perfusion or slower microvascular response to exercise are more vulnerable when perfusion is impaired as result of a disease. Therefore, covering larger imaging volumes is of great interest when assessing microvascular response to exercise.…”