Effect of hyperbaric oxygen therapy on the healing of leg ulcers in sickle cell patients: functional and mechanistic characterization
The project will focus on 2 main axes.
The first will aim at the therapeutic evaluation of the hyperbaric chamber on the healing of ulcers in sickle cell patients. A few reported cases and the experience of physicians support a low grade recommendation from the Hyperbaric Medicine Society for the use of hyperbaric oxygen therapy in this indication. As a preliminary, we plan to carry out a functional characterization of the cutaneous microcirculation of sickle cell patients (upper third of the tibial ridge) with and without ulcers. Cutaneous blood flow will be measured by Doppler laser in response to local heating and iontophoretic administration of acetylcholine to study endothelial function. We plan to subsequently evaluate the effectiveness of hyperbaric oxygen sessions on the healing of leg ulcers. The primary endpoint will be the proportion of patients whose ulcer has healed 24 weeks after inclusion. In addition, the functional microvascular characterization will be carried out by the same method, at the start and at the end of hyperbaric oxygen sessions to assess the impact on endothelial function. We are also planning an initial blood sample and then at the end of the hyperbaric oxygen treatment to characterize the plasma cytokines and study the rheology using the oxygencan module on the ektacytometer.
The second axis will seek to characterize the phenotype of exudate from leg ulcers collected with blotters and study its effect on cell cultures of endothelial cells and fibroblasts. Various markers will be analyzed in the exudates: content of cytokines, metalloproteases, oxidative stress markers, etc. known in the literature as limiting healing. The exudates of patients treated with a chamber will also be analyzed. Secondly, the effect of these identified markers will be analyzed on cell cultures of endothelial cells and fibroblasts. The effect of these identified markers on the healing of skin wounds in murine sickle cell models can also be analyzed.
