Angiogenic effects of low-intensity cathodal direct current on ischemic diabetic foot ulcers: A randomized controlled trial

Aims: This study investigated the effect of low-intensity cathodal direct current (CDC) of electrical stimulation (ES) on the release of hypoxic inducible factor-1 alpha (HIF-1 alpha), nitric oxide (NO), vascular endothelial growth factor (VEGF), and soluble VEGF receptor-2 (sVEGFR-2) in the wound fluid of ischemic diabetic foot ulcers (DFUs). Methods: This study was a randomized, single-blind, placebo-controlled trial. Thirty type 2 diabetes patients with ischemic foot ulcerations were randomly assigned to receive either low-intensity CDC at sensory threshold (ES group, n = 15) or placebo treatment (control group, n = 15) for 1 h/day, 3 days/week, for 4 weeks (12 sessions). After debridement during the first and twelfth treatment sessions, wound fluid was collected before and after ES application to determine the levels of HIF-1 alpha, NO, VEGF, and sVEGFR-2. Wound surface area (WSA) was measured at the first, sixth, and twelfth sessions. Results: At the first session, after ES application, wound-fluid levels of HIF-1 alpha were significantly increased (=61.98 pg/mL) compared to the control group (-3.85 pg/mL, P = 0.01). After ES application at the first and twelfth sessions, wound-fluid levels of VEGF were also significantly increased (+36.77 and +39.57 pg/mL, respectively) compared to the control group (+4.15 and +0.15 pg/mL, P = 0.007 and P = 0.019, respectively). There was no significant effect on NO and sVEGFR-2 levels between the groups. Conclusions: Low-intensity CDC has positive effects on the release of HIF-1 alpha and VEGF in the wound area of ischemic DFUs. Furthermore, our results suggest that applying ES to ischemic DFUs can be a promising way to promote angiogenesis and to achieve better outcomes in diabetic wound healing. (C) 2017 Elsevier B.V. All rights reserved.