CO2 WATER-BATH AS A NOVEL THERAPY FOR THE TREATMENT OF PERIPHERAL ARTERY DISEASE IN DIABETES



Naranjan S. Dhalla, Ph.D., M.D., Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada

Background and Objectives: Peripheral artery disease is commonly seen in diabetic subject; however, no satisfactory intervention is available for its treatment. This study examined the effects of CO2 water-bath therapy on blood flow in the ischemic hind limb of diabetic animals.

Methods: Diabetes in rats was induced by streptozotocin (65 mg/kg) and two weeks later, ischemia in the limb was induced by ligating the femoral artery for a period of 2 weeks. Diabetic ischemic animals were subjected to water-bath (37°C) treatment with or without CO2 therapy for 6 weeks (30 min/day for 5 days/week). Diabetic ischemic animals without water-bath treatment served as control. Blood flow in the ischemic hind limb was measured by the Pulse Wave Doppler System whereas angiogenesis in the skeletal muscle was evaluated histologically.

Results and Discussion: Both peak and mean blood flow in the ischemic limb were increased by the CO2 water-bath therapy without any changes in the minimum blood flow. Furthermore, angiogenesis was markedly promoted by the CO2 water-bath treatment. These alterations by CO2 bath therapy were not associated with any changes in heart rate as well as plasma glucose, cholesterol, triglyceride and high density lipoprotein levels. The depressed levels of plasma oxidized low density lipoproteins (Ox-LDL) were further decreased whereas the elevated levels of plasma NO were further increased without any changes in the increased plasma levels of malondialdehyde by CO2 water-bath treatment.

Conclusions: These results indicate the improvement of blood flow and development of angiogenesis in diabetic ischemic limb by CO2 water treatment were associated with increase in the formation of NO as well as reduction in the level of Ox-LDL. It is suggested that CO2 water-bath therapy is beneficial for the treatment of peripheral artery disease in diabetes. (Infrastructure support for this study was provided by the St. Boniface Hospital Foundation)