Investigation of in vivo measurement of cerebral cytochrome-c-oxidase redox changes using near-infrared spectroscopy in patients with orthostatic hypotension

We have previously used a continuous four-wavelength near-infrared spectrometer to measure changes in the cerebral concentrations of oxyhaemoglobin (Delta[HbO(2)] and deoxy-haemoglobin (Delta[HHb]) during head-up tilt in patients with primary autonomic failure. The measured changes in light attenuation also allow calculation of changes in the concentration of oxidized cytochrome-c-oxidase (Delta[oxCCO]), and this paper analyses the Delta[oxCCO] during the severe episodes of orthostatic hypotension produced by this experimental protocol. We studied 12 patients during a passive change in position from supine to a 60 degrees head-up tilt. The challenge caused a reduction in mean blood pressure of 59.93 (+/- 26.12) mmHg (Mean (+/- SD), p < 0.0001), which was associated with a reduction in the total concentration of haemoglobin (Delta[HbT] = Delta[HbO(2)] + Delta[HHb]) of 5.02 (+/- 3.81) mu M (p < 0.0001) and a reduction in the haemoglobin difference concentration (Delta[Hb(diff)]= Delta[HbO(2)]-[ Delta[HHb]) of 14.4 (+/- 6.73) mu M (p < 0.0001). We observed a wide range of responses in Delta[oxCCO]. Six patients demonstrated a drop in Delta[oxCCO] (0.17 +/- 0.15 mu M); four patients demonstrated no change (0.01 +/- 0.12 mu M) and two patients showed an increase in Delta[oxCCO] (0.21 +/- 0.01 mu M). Investigation of the association between the changes in concentrations of haemoglobin species and the Delta[oxCCO] for each patient show a range of relationships. This suggests that a simple mechanism for crosstalk, which might produce artefactual changes in [oxCCO], is not present between the haemoglobin and the oxCCO NIRS signals. Further investigation is required to determine the clinical significance of the changes in [oxCCO].