Normal muscle oxygen consumption and fatigability in sickle cell patients despite reduced microvascular oxygenation and hemorheological abnormalities

Abstract

Background/aim: Although it has been hypothesized that muscle metabolism and fatigability could be impaired in sickle cell patients, no study has addressed this issue.

Methods: We compared muscle metabolism and function (muscle microvascular oxygenation, microvascular blood flow, muscle oxygen consumption and muscle microvascular oxygenation variability, which reflects vasomotion activity, maximal muscle force and local muscle fatigability) and the hemorheological profile at rest between 16 healthy subjects (AA), 20 sickle cell-hemoglobin C disease (SC) patients and 16 sickle cell anemia (SS) patients.

Results: Muscle microvascular oxygenation was reduced in SS patients compared to the SC and AA groups and this reduction was not related to hemorhelogical abnormalities. No difference was observed between the three groups for oxygen consumption and vasomotion activity. Muscle microvascular blood flow was higher in SS patients compared to the AA group, and tended to be higher compared to the SC group. Multivariate analysis revealed that muscle oxygen consumption was independently associated with muscle microvascular blood flow in the two sickle cell groups (SC and SS). Finally, despite reduced muscle force in sickle cell patients, their local muscle fatigability was similar to that of the healthy subjects.

Conclusions: Sickle cell patients have normal resting muscle oxygen consumption and fatigability despite hemorheological alterations and, for SS patients only, reduced muscle microvascular oxygenation and increased microvascular blood flow. Two alternative mechanisms can be proposed for SS patients: 1) the increased muscle microvascular blood flow is a way to compensate for the lower muscle microvascular oxygenation to maintain muscle oxygen consumption to normal values or 2) the reduced microvascular oxygenation coupled with a normal resting muscle oxygen consumption could indicate that there is slight hypoxia within the muscle which is not sufficient to limit mitochondrial respiration but increases muscle microvascular blood flow.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Muscle microvascular oxygen saturation (TOI) at rest in AA, SC and SS groups.

Different from AA group (*p†p<0.05).

Figure 2. Forearm blood flow at rest (2a) and muscle oxygen consumption at rest (2b) in AA, SC and SS groups.

Figure 3. Fast Fourier Transform analysis of TOI signal variability.

Total power spectral density (3a, flowmotion activity), power spectral density in interval I, II and III (3b, vasomotion activity), power spectral density in interval IV, V (3c) and normalized spectral density (3d). Interval I = endothelial activity and/or nitric oxide metabolism, interval II = nervous sympathetic activity of the vessel wall, interval III = myogenic activity, interval IV = breathing frequency and interval V heart rate and cardiac output.

Figure 4. Example of Fast Fourier Transform analysis of TOI signal variability in one AA subject (left), one SC patient (middle) and one SS patient (right).

The frequency axis is divided into three parts: vasomotion activity (left), interval IV (middle), and interval V (right). Note that the scale of the Y-axis is different for the three subjects.