Respiratory and locomotor muscle blood flow measurements using near-infrared spectroscopy and indocyanine green dye in health and disease

Abstract

Measuring respiratory and locomotor muscle blood flow during exercise is pivotal for understanding the factors limiting exercise tolerance in health and disease. Traditional methods to measure muscle blood flow present limitations for exercise testing. This article reviews a method utilising near-infrared spectroscopy (NIRS) in combination with the light-absorbing tracer indocyanine green dye (ICG) to simultaneously assess respiratory and locomotor muscle blood flow during exercise in health and disease. NIRS provides high spatiotemporal resolution and can detect chromophore concentrations. Intravenously administered ICG binds to albumin and undergoes rapid metabolism, making it suitable for repeated measurements. NIRS-ICG allows calculation of local muscle blood flow based on the rate of ICG accumulation in the muscle over time. Studies presented in this review provide evidence of the technical and clinical validity of the NIRS-ICG method in quantifying respiratory and locomotor muscle blood flow. Over the past decade, use of this method during exercise has provided insights into respiratory and locomotor muscle blood flow competition theory and the effect of ergogenic aids and pharmacological agents on local muscle blood flow distribution in COPD. Originally, arterial blood sampling was required via a photodensitometer, though the method has subsequently been adapted to provide a local muscle blood flow index using venous cannulation. In summary, the significance of the NIRS-ICG method is that it provides a minimally invasive tool to simultaneously assess respiratory and locomotor muscle blood flow at rest and during exercise in health and disease to better appreciate the impact of ergogenic aids or pharmacological treatments.

Keywords: Muscle blood flow; chronic obstructive pulmonary disease; near-infrared spectroscopy.

Figure 1.

Schematic representation of the NIRS-ICG technique. From top left to bottom: an intravenous bolus of ICG is administered intravenously, it passes through the heart and lungs through the venous circulation, then via the arterial circulation it enters the systemic circulation and microcirculation. The NIRS optodes which are positioned over the vastus lateralis muscle, detect the ICG concentration. Extinction coefficients in a matrix operation are employed, and the ICG curve is isolated. The circles represent the NIRS optodes positioned over the muscle tissue. Output from one NIRS channel, showing the indocyanine green (ICG) dye signal (yellow) following intravenous ICG injection marked by the purple arrow. Green trace [tissue oxygenation index (TOI)] is the oxygenation signal. (Output from NIRS channels was reproduced from Vogiatzis I. et al., 2015; Journal of Applied Physiology, 118 (6), p783-793).

Figure 2.

(a) Example of Blood Flow Index calculation; (b) Regression analyses of Blood FIow Index (BFI) versus local muscle blood flow for intercostal (filed symbols, black line) and quadriceps (open symbols, grey line) muscles; r = 0.98 for intercostal and 0.96 for quadriceps muscle. p < .001 for both muscles. (Reproduced from original data from Guenette et al., 2008; Journal of Applied Physiology, 104 (4), p1202-1210).

Figure 3.

Association between intercostal muscle blood flow and the rate of respiratory muscle work across different levels of minute ventilation during resting isocapnic hyperpnoea (black symbols) and graded incremental exercise (coloured symbols) in healthy subjects. (Reproduced from original data from Vogiatzis et al., 2009; J Physiol, 587 (14), p3665-3677).

Figure 4.

Intercostal and quadriceps muscle blood flow at baseline (B) and across different levels of cycling exercise to the limit of tolerance. Data obtained from athletes. Values are means ± SEM. (Reproduced from original data from Habazettl et al., 2010; Journal of Applied Physiology, 108 (4), p962-967).

Figure 5.

Intercostal and quadriceps muscle blood flow during exercise (open triangles) and resting isocapnic hyperpnoea (closed triangles) in patients with COPD.(Reprinted with permission of the American Thoracic Society. Copyright © 2024 American Thoracic Society. All rights reserved. Vogiatzis et al., 2010; Intercostal muscle blood flow limitation during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 182(9), p1105-1113. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society).

Figure 6.

Intercostal, abdominal and quadriceps muscle blood flow during exercise; open triangles indicate hyperoxia, closed circles indicate normoxia and open squares indicate heliox, in COPD patients. Isotime: the time point where exercise in normoxia was terminated. (Reproduced from original data from Louvaris et al., 2014; Journal of Applied Physiology, 117 (3), p267-276).