Quantitative assessment of cytochrome C oxidase patterns in muscle tissue by the use of near-infrared spectroscopy (NIRS) in healthy volunteers

Abstract

Cytochrome C oxidase (CCO) acts as final electron acceptor in the respiratory chain, possibly providing information concerning cellular oxygenation. CCO is a chromophore with a broad absorption peak in the near-infrared spectrum in its reduced state (835 nm). However, this peak overlaps with deoxygenated haemoglobin (HHb; 755 nm) which is present in much higher concentrations. NIRO-300 measures CCO signals, but did not receive FDA approval for this use due to presumed lack of independency of the measured CCO changes. However, there is no proven evidence for this assumption. We hypothesized that the NIRO-300 provides a HHb independent measurement of CCO concentration changes. In this single-center crossover randomized controlled trial in healthy volunteers, subjects were randomized to receive arterial occlusion to the left arm and venous stasis on the right arm (n = 5) or vice versa (n = 5) during 5 min. After a resting period, the second part of the cross over study was performed. We placed the NIRO-300 optodes bilateral at the level of the brachioradial muscle in order to collect NIRS data continuously. Data was analysed using a generalized additive mixed model. HHb and CCO follow a significant different trend over time during the intervention period for both arterial occlusion (F = 20.645, edf = 3.419, p < 0.001) and venous stasis (F = 9.309, edf = 4.931, p < 0.001). Our data indicate that CCO concentration changes were not affected by HHb changes, thereby proving independency.Clinical trial registration: B670201732023 on June 28, 2017.

Keywords: Cellular oxygenation; Cytochrome C oxidase; NIRO-300; NIRS.