Normal Muscle Oxygen Consumption and Fatigability in Sickle Cell Patients Despite Reduced Microvascular Oxygenation and Hemorheological Abnormalities

Abstract

Background/AimAlthough it has been hypothesized that muscle metabolism and fatigability could be impaired in sickle cell patients, no study has addressed this issue.MethodsWe 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.ResultsMuscle 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.ConclusionsSickle 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.

Hematological and hemorheological Determinants of the Six-Minute Walk Test Performance in Children with Sickle Cell Anemia

“…We recently reported that despite reduced hemoglobin concentration and hematocrit level in SCA patients, the local resting muscle oxygen consumption is comparable between SCA patients and healthy subjects because the local resting microvascular blood flow is increased in the former population [25]. Although the hemodynamic compensation for chronic anemia may be sufficient to normalize muscle oxygen consumption at rest, this is not the case during exercise where the needs for oxygen gradually increase with the intensity.…”

Hematologic and hemorheological determinants of resting and exercise-induced hemoglobin oxygen desaturation in children with sickle cell disease

“…20,22,23,39 Therefore, SC and SS children were analyzed separately. Part of the results described here were previously included in a report on the initial SAPOTILLE cohort.…”

Skeletal and myocardial microvascular blood flow in hydroxycarbamide‐treated patients with sickle cell disease

“…Leg blood flow studies in young healthy men following acute lowering of haemoglobin concentration have demonstrated increased systemic and muscle blood flow (Koskolou et al, 1997;Gonzalez-Alonso et al, 2006)). Studies using strain gauge plethysmography (Eberhardt et al, 2003)and near infra-red spectroscopy (Waltz et al, 2012) have consistently shown increased resting overall forearm blood flow in SCD patients compared with controls. Animal studies of non-SCD anaemia show that resting skeletal muscle microvascular flow is significantly higher in the anaemic state compared with controls (Kubes et al, 1988).…”