Mechanisms of the Increase in Peripheral Blood Flow in Diabetic Animals with or Without Ischemia

Earlier studies have revealed that CO₂ water-bath therapy improve the blood flow and promote the occurrence of angiogenesis in the ischemic limb. This study was undertaken to investigate the effects of CO₂ water-bath therapy in diabetic rats with or without hind limb ischemia. Diabetes in rats was induced by an injection of streptozotocin (65 mg/kg) and two weeks later, the hind limb was made ischemic by ligation of the femoral artery for 2 weeks. After 4 weeks of inducing diabetes, these animals were treated with or without CO₂ water-bath (37°C) therapy for 6 weeks (30 min/day for 5 days/week). CO₂ water-bath therapy promoted the peak and mean blood flow as well as angiogenesis without any changes in the minimum blood flow in the hind limb of both diabetic and diabetic ischemic animals. CO₂ water-bath treatment did not affect plasma cholesterol, triglyceride and high density lipoprotein levels. Plasma levels of oxidized low density lipoproteins (Ox-LDL) were decreased in both diabetic and diabetic ischemic animals; however, CO₂ therapy further reduced the OX-LDL in the diabetic-ischemic group. CO₂ water-bath treatment did not show any effect on plasma levels of NO in diabetic animals or plasma MDA levels in diabetic ischemic group. While the decrease in MDA levels in diabetic rats was not affected, the increase in NO level in diabetic ischemic animals was further increased by CO₂ therapy. These results suggest that CO₂ water-bath treatment may exert beneficial effect in peripheral artery disease in diabetes by promoting blood flow and angiogenesis.