Reproducibility of NIRS assessment of muscle oxidative capacity in smokers with and without COPD

Abstract

Low muscle oxidative capacity contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). Near-infrared spectroscopy (NIRS) allows non-invasive determination of the muscle oxygen consumption (mV̇O₂) recovery rate constant (k), which is proportional to oxidative capacity assuming two conditions are met: 1) exercise intensity is sufficient to fully-activate mitochondrial oxidative enzymes; 2) sufficient O₂ availability. We aimed to determine reproducibility (coefficient of variation, CV; intraclass correlation coefficient, ICC) of NIRS k assessment in the gastrocnemius of 64 participants with (FEV₁ 64±23%predicted) or without COPD (FEV₁ 98±14%predicted). 10-15s dynamic contractions preceded 6min of intermittent arterial occlusions (5-10s each, ∼250mmHg) for k measurement. k was lower (P<0.05) in COPD (1.43±0.4min^-1; CV=9.8±5.9%, ICC=0.88) than controls (1.74±0.69min^-1; CV=9.9±8.4%; ICC=0.93). Poor k reproducibility was more common when post-contraction mV̇O₂ and deoxygenation were low, suggesting insufficient exercise intensity for mitochondrial activation and/or the NIRS signal contained little light reflected from active muscle. The NIRS assessment was well tolerated and reproducible for muscle dysfunction evaluation in COPD.

Keywords: Exercise intolerance; Kinetics; Mitochondria; Oxygen consumption; Quality-control; Skeletal muscle.

Figure 1. Tissue saturation index (TSI, %) changes during the NIRS muscle assessment

Panel A. Protocol phases, and the parameter calculated from the analyses of TSI signal changes, are indicated at the bottom of the graph. Grey shading indicates brief dynamic plantar-flexion exercise. AO = arterial occlusion; max and min = highest and lowest TSI values during the Physiologic Normalization (PN) phase; TSI_LOW = lowest saturation value reached during oxidative capacity assessments (for further details see Methods). Panel B. Expansion of panel A to illustrate the linear regression to determine the deflection point of muscle TSI (arrow) during the sustained arterial occlusion (AO). Grey shading indicates brief dynamic plantar-flexion exercise.

Figure 2. Representative COPD (A, B) and control (C, D) participants’ responses during the muscle oxidative capacity assessment

Panels A and C show the TSI profiles during dynamic exercise, and intermittent arterial occlusion during recovery. Panels B and D show the calculated muscle ${\dot{\mathrm{V}}\mathrm{O}}_{\mathrm{2}}$ recovery profiles and kinetic fit (dashed line). The letters (a–e) are given to illustrate how the corresponding ${\mathrm{m}\dot{\mathrm{V}}\mathrm{O}}_{\mathrm{2}}$ value is derived from respective TSI negative slopes during intermittent occlusions. The grey area (EX) indicates the brief dynamic exercise. τ (s) is the ${\mathrm{m}\dot{\mathrm{V}}\mathrm{O}}_{\mathrm{2}}$ time constant determined by non-linear least-squares regression. k, is the rate constant, which is linearly related to muscle oxidative capacity (k = (1/τ).60, min⁻¹).

Figure 3. Muscle oxidative capacity (k) test-retest analyses

Comparison of muscle k inferred from the two repetitions of muscle ${\dot{\mathrm{V}}\mathrm{O}}_{\mathrm{2}}$ recovery kinetics in COPD (n = 28) and controls, CON (n = 28). Continuous line is the linear regression. Dotted line is the line of identity (x = y).

Figure 4. Bland-Altman plot of the agreement between repeated measurements of muscle V˙O2 recovery rate constant (k)

Closed symbols are COPD patients (n = 28) and open symbols are controls (CON, n = 28). Horizontal dashed lines indicate the 95% limits of agreement (range −0.58, 0.64 min⁻¹).