Mohammad Reza Asadi1, Giti Torkaman2, Mehdi Hedayati3, Mohammad Reza Mohajeri-Tehrani4, Mousa Ahmadi5, Roghieh Fathi Gohardani6. 1. Department of Physical Therapy, School of Rehabilitation Sciences, Hamadan University of Medical Sciences, Hamadan, Iran; Physical Therapy Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. 2. Physical Therapy Department, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: torkamg@modares.ac.ir. 3. Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 4. Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran. 5. Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran. 6. Hajar Hospital, Tehran, Iran.
Abstract
AIMS: This study investigated the effect of low-intensity cathodal direct current (CDC) of electrical stimulation (ES) on the release of hypoxic inducible factor-1α (HIF-1α), 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 1h/day, 3days/week, for 4weeks (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-1α, 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-1α were significantly increased (+61.98pg/mL) compared to the control group (-3.85pg/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 +39.57pg/mL, respectively) compared to the control group (+4.15 and +0.15pg/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-1α 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.
RCT Entities:
AIMS: This study investigated the effect of low-intensity cathodal direct current (CDC) of electrical stimulation (ES) on the release of hypoxic inducible factor-1α (HIF-1α), 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 diabetespatients 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 1h/day, 3days/week, for 4weeks (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-1α, 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-1α were significantly increased (+61.98pg/mL) compared to the control group (-3.85pg/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 +39.57pg/mL, respectively) compared to the control group (+4.15 and +0.15pg/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-1α 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.