Preventing Flap Necrosis with Adrenomedullin and Glucagon-like Peptide-1

SLR - June 2012 - Jamie L. Hall

Reference: Betual Cam Etoz, MD; Naciye Isbil Buyukcoskun, PhD; Abdullah Etoz, MD; Kasim Ozluk, PhD.  Wounds: A Compendium of Clinical Research and Practice, 24(2):29-34

Scientific Literature Review

Reviewed by:  Jamie L. Hall, DPM
Residency Program:  OCPM & University Hospital Richmond Heights Medical Center

Podiatric Relevance: 
Wounds are one of the most difficult problems podiatrists face. As the diabetic population increases, so does the number of patients with ulcerations. Treatment of wounds can vary greatly, but they all require one basic need: oxygen from blood. This article compares the effects of Adrenomedullin (ADM) and Glucagon-like Peptide-1 (GLP-1) on blood flow and tissue flap necrosis. 

Methods: 
For this clinically based study, 48 Wistar rats within a fixed weight range were used. The group of 48 was divided into four groups: Sham, Saline, ADM, GLP-1. Each rat underwent abdominal wall surgery where an 8 cm by 3 cm cutaneous flap was lifted. Each abdomen flap was lifted based on the superficial inferior epigastric artery (SIEA) and divided into four quadrants. Each flap was then re-sutured into place and a laser doppler flow meter was used to evaluate the blood supply to each quadrant for a baseline perfusion. Injections of the selected solution were then made into the femoral artery. After 10 minutes, the flap pedicle was measured again. Measurements were recorded as tissue perfusion units. The difference in perfusion rates were shown as a percent change. Post-op day number seven, each flap was photographed at set distance and the photographs were evaluated in a blind manner. The size of each flap tissue and the necrotic area was measured to determine a percentage of flap necrosis.

Results:  
Groups treated with ADM or GLP-1 showed a statistically significant increase in the blood flow to the four quadrants of the re-sutured flap compared to the saline and sham groups. There was no statistically significant difference in the groups treated with ADM and GLP-1. No statistical difference was noted between high-dose ADM and GLP-1 groups, however, the amount of necrosis was decreased from that seen in the saline group.

Conclusions: 
While this study was performed on rats, the potential for use in humans to increase blood flow and decrease necrosis is great. Necrosis that develops with flaps is typically seen in the distal region where vascularity is lowest. Both peptides demonstrated the ability to increase blood flow to these areas. GLP-1 and ADM have both been shown to increase vasodilation in humans. GLP-1 has also been shown to have anti-apoptotic effects that decreases necrosis. ADM and GLP-1 show promising results to increase blood flow and decrease necrosis in the normal flap recovery process. This could translate into a much needed treatment for wounds as well as for the preservation of skin flaps used in podiatric medicine.