Capillary‐to‐sarcolemma distance and location of cytochrome <i>c</i> oxidase: Insights for maximal O₂ uptake and muscle lactate release in trained athletes

Mean capillary-to-sarcolemma diffusion distance (mCtSDD) is conceptually critical for exchanges of both gases and metabolites between muscle and blood. However, the importance of this distance for maximal oxygen uptake ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mrow><mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> <mml:mi>max</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_2}{\mathrm{max}}}}$</mml:annotation></mml:semantics> </mml:math> ) and muscle lactate release in highly-trained athletes remains unexplored. Furthermore, the importance of intramyocyte location of cytochrome c oxidase (COx) activity and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mrow><mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> <mml:mi>max</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_2}{\mathrm{max}}}}$</mml:annotation></mml:semantics> </mml:math> remains obscure. Seventeen highly-trained lightweight oarsmen performed a maximal incremental exercise test to assess <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mrow><mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> <mml:mi>max</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_2}{\mathrm{max}}}}$</mml:annotation></mml:semantics> </mml:math> and its associated power ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:msub><mml:mi>P</mml:mi> <mml:mrow><mml:mi>a</mml:mi> <mml:mspace></mml:mspace> <mml:mi>max</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${P_{{\mathrm{a\;max}}}}$</mml:annotation></mml:semantics> </mml:math> ), as well as a 3 min 110% <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics><mml:msub><mml:mi>P</mml:mi> <mml:mrow><mml:mi>a</mml:mi> <mml:mspace></mml:mspace> <mml:mi>max</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${P_{{\mathrm{a\;max}}}}$</mml:annotation></mml:semantics> </mml:math> exercise to estimate the net lactate release rate at exercise completion [NLRR(0)]. A vastus lateralis muscle biopsy allowed analysis of muscle microvasculature indices [capillary density (CD) and mCtSDD] and location-specific COx activity. Significant correlations between mCtSDD and both <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mrow><mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> <mml:mi>max</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_2}{\mathrm{max}}}}$</mml:annotation></mml:semantics> </mml:math> (r = -0.76, P < 0.001) and NLRR(0) (r = -0.63, P = 0.00724) were found. Correlations between CD and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mrow><mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> <mml:mi>max</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_2}{\mathrm{max}}}}$</mml:annotation></mml:semantics> </mml:math> or NLRR(0) were also found (r = 0.50, P = 0.0397 and r = 0.49, P = 0.0483, respectively). COx activity was higher in the pericapillary and subsarcolemmal domains than in the intramyofibrillar counterpart (location effect: P < 0.001). Pericapillary and subsarcolemmal COx activities were significantly associated with <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mrow><mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> <mml:mi>max</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_2}{\mathrm{max}}}}$</mml:annotation></mml:semantics> </mml:math> (r = 0.59, P = 0.0322 and r = 0.58, P = 0.0387, respectively), in contrast to its intramyofibrillar counterpart (r = 0.48, P = 0.096). mCtSDD was significantly associated with <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mrow><mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> <mml:mi>max</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_2}{\mathrm{max}}}}$</mml:annotation></mml:semantics> </mml:math> and muscle lactate release rate in highly-trained endurance athletes. Pericapillary and subsarcolemmal COx activity was also associated with <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mrow><mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> <mml:mi>max</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_2}{\mathrm{max}}}}$</mml:annotation></mml:semantics> </mml:math> . KEY POINTS: Because it is a carrier-free area, the capillary-to-sarcolemma diffusion distance is conceptually critical for exchanges of both gases and metabolites between muscle and blood. In the present study, we proposed a new index estimating the mean capillary-to-sarcolemma diffusion distance (mCtSDD). In the present study, mCtSDD was closely correlated with <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mrow><mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> <mml:mi>max</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_2}{\mathrm{max}}}}$</mml:annotation></mml:semantics> </mml:math> and the net lactate release rate estimated at exercise completion. The importance of intramyocyte location of cytochrome c oxidase (COx) activity and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mrow><mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> <mml:mi>max</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_2}{\mathrm{max}}}}$</mml:annotation></mml:semantics> </mml:math> remains obscure in highly-trained athletes. Pericapillary and subsarcolemmal COx activity was higher than its intermyofbrillar counterpart. Pericapillary and subsarcolemmal COx activity was significantly associated with <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:msub><mml:mover><mml:mi>V</mml:mi> <mml:mo>̇</mml:mo></mml:mover> <mml:mrow><mml:msub><mml:mi>O</mml:mi> <mml:mn>2</mml:mn></mml:msub> <mml:mi>max</mml:mi></mml:mrow> </mml:msub> <mml:annotation>${\dot V_{{{\mathrm{O}}_2}{\mathrm{max}}}}$</mml:annotation></mml:semantics> </mml:math> in highly-trained endurance athletes.