Carbon Dioxide–Rich Water Bathing Enhances Collateral Blood Flow in Ischemic Hindlimb via Mobilization of Endothelial Progenitor Cells and Activation of NO-cGMP System

Abstract

Background-Carbon dioxide-rich water bathing has the effect of vasodilatation, whereas it remains undetermined whether this therapy exerts an angiogenic action associated with new vessel formation. Methods and Results-Unilateral hindlimb ischemia was induced by resecting the femoral arteries of C57BL/J mice.Lower limbs were immersed in CO 2 -enriched water (CO 2 concentration, 1000 to 1200 mg/L) or freshwater (control) at 37°C for 10 minutes once a day. Laser Doppler imaging revealed increased blood perfusion in ischemic limbs of CO 2 bathing (38% increase at day 28, PϽ0.001), whereas N G -nitro-L-arginine methyl ester treatment abolished this effect. Angiography or immunohistochemistry revealed that collateral vessel formation and capillary densities were increased (4.1-fold and 3.7-fold, PϽ0.001, respectively). Plasma vascular endothelial growth factor (VEGF) levels were elevated at day 14 (18%, PϽ0.05). VEGF mRNA levels, phosphorylation of NO synthase, and cGMP accumulation in the CO 2 -bathed hindlimb muscles were increased (2.7-fold, 2.4-fold, and 3.4-fold, respectively) but not in forelimb muscles. The number of circulating LinϪ/Flk-1ϩ/CD34Ϫ endothelial-lineage progenitor cells was markedly increased by CO 2 bathing (24-fold at day 14, PϽ0.001). The LinϪ/Flk-1ϩ/CD34Ϫ cells express other endothelial antigens (endoglin and VE-cadherin) and incorporated acetylated LDL. Conclusions-Our present study demonstrates that CO 2 bathing of ischemic hindlimb causes the induction of local VEGF synthesis, resulting in an NO-dependent neocapillary formation associated with mobilization of endothelial progenitor cells.

Immersing Feet in Carbon Dioxide-enriched Water Prevents Expansion and Formation of Ischemic Ulcers after Surgical Revascularization in Diabetic Patients with Critical Limb Ischemia

“…Using experimental animals, it has been shown that CO 2 immersion results in a NO-dependent increase in collateral blood perfusion, induction of regional VEGF synthesis, and mobilization of endothelial-lineage progenitor cells into the circulation. 9) These results suggest that CO 2 immersion improves subcutaneous microcirculation.…”

“…The CO 2 -enriched water is made with an extra corporeal circulation system (MRE-SPA-MD, Mitsubishi Rayon Engineering, Tokyo, Japan). 8,9) It can instantly enrich 5 L/min of tap water (pH 6.8) with CO 2 (free CO 2 concentration, 1,000 to 1,200 mg/l, pH 4.6). Patients recorded the immersion dates, which were confirmed by the investigators.…”

The effect of carbonated mineral water and mofette treatment in Baile Tusnad after ischemic stroke – a case report

“…Carbon dioxide baths might represent an effective therapeutic method in the rehabilitation of coronary heart disease, myocardial infarction and stroke, as well as in the treatment of chronic venous insufficiency, inflammatory diseases and functional disorders [2,3]. Carbonated mineral water baths are considered to be effective in the treatment of peripheral vascular disorders [4].…”

Use of Transcutaneous Application of CO2 in Diabetic Foot Pathology

“…The increased perivascular pO 2 was due to the effect of CO 2 on the oxyhemoglobin dissociation curve. Irie et al [2] demonstrated that CO 2 immersion induced the production of plasma vascular endothelial growth factor (VEGF), resulting in no-dependent angiogenesis associated with the mobilization of endothelial progenitor cells. Hayashi et al [3] showed that CO 2 immersion increased blood flow in feet to a much higher extent than plain water and it improved the limb salvage rate in critical limb ischemia patients without the option of revascularization.…”