Abstract

Background: This study tested the hypothesis that hyperbaric oxygen (HBO) therapy enhanced the circulating levels of endothelial progenitor cells (EPCs), soluble angiogenesis factors, and blood flow in ischemic areas in patients with peripheral arterial occlusive disease (PAOD). Methods: In total, 57 consecutive patients with PAOD undergoing the HBO therapy (3 atmospheres (atm) for 2 h each time) were prospectively enrolled into the present study. Venous blood sampling was performed to assess the circulating levels of EPCs and soluble angiogenesis factors prior to and during five sessions of HBO therapy. Additionally, skin perfusion pressure (SPP), an indicator of blood flow in ischemic areas, was measured by moorVMS-PRES. Results: The results demonstrated that the circulating levels of EPCs (cluster of differentiation (CD)34+/CD133+/CD45dim, CD31+/CD133+/CD45dim, CD34+) and soluble angiogenesis factors—vascular endothelial growth factor/stromal cell-derived factor 1/hepatocyte growth factor/fibroblast growth factor (VEGF/SDF-1α/HGF/FGF) were significantly increased post-HBO therapy as compared to pre-HBO therapy (all p < 0.01). Additionally, Matrigel assay showed that the angiogenesis was significantly increased in post-HBO therapy as compared to prior to therapy (p < 0.001). Furthermore, SPP was significantly increased in the ischemic area (i.e., plantar foot and mean SPP of the ischemic foot) in post-HBO therapy as compared to pre-HBO therapy (all p < 0.01). Importantly, the HBO therapy did appear to result in complications, and all the patients were uneventfully discharged without amputation. Conclusions: HBO therapy augmented circulating levels of EPCs and angiogenesis factors, and improved the blood flow in the ischemic area.

Highlights

  • Arterial atherosclerotic occlusive syndrome (AAOS) remains the leading cause of mortality and morbidity worldwide

  • The recent data available from a screening trial of Danish men aged 65 to 74 years reported that the prevalence of peripheral arterial occlusive disease (PAOD) was 11% when PAOD was defined as the presence of an ankle–brachial index (ABI) of less than 0.9 or greater than 1.4 [5]

  • This study, which investigated the therapeutic impact of hyperbaric oxygen (HBO) therapy with respect to circulatory angiogenesis factors and blood flow in ischemic areas, yielded several striking implications

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Summary

Introduction

Arterial atherosclerotic occlusive syndrome (AAOS) remains the leading cause of mortality and morbidity worldwide. The recent data available from a screening trial of Danish men aged 65 to 74 years reported that the prevalence of PAOD was 11% when PAOD was defined as the presence of an ankle–brachial index (ABI) of less than 0.9 or greater than 1.4 [5] Another recent report [6] found that over 5 years of follow-up approximately 7% of patients with asymptomatic PAOD developed intermittent claudication and approximately 21% of patients with intermittent claudication progressed to critical limb ischemia, with a 5-year cumulative incidence of cardiovascular mortality of 9% [6]. This study tested the hypothesis that hyperbaric oxygen (HBO) therapy enhanced the circulating levels of endothelial progenitor cells (EPCs), soluble angiogenesis factors, and blood flow in ischemic areas in patients with peripheral arterial occlusive disease (PAOD). Conclusions: HBO therapy augmented circulating levels of EPCs and angiogenesis factors, and improved the blood flow in the ischemic area

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