Single‐pedicled Fasciocutaneous Flap Survival In Aged Rat Model of Chronic Alcoholism

Abstract

Impact of chronic ethanol consumption on signaling events underlying composite pedicled flap survival was examined in isocaloric pair-fed Sprague-Dawley rats that consumed Lieber-DeCarli '82 liquid 1000 kcal/L diet consisting of 15.1% protein, 35.9% fat and either 49% carbohydrates (control group) or 13.5% carbohydrates and 35.5% ethanol (alcoholic group). Six pairs of rats that were fed such diet for at least one year underwent surgery, where a 3:8 width to length ratio pedicled fasciocutaneous flap based on the inferior epigastric artery was raised in each rat and rotated into a defect created in the ventral surface. Tissue from the contralateral recipient site was snap-frozen to serve as baseline (day 0) for comparison with the flap harvested on 9th post-operative day. The endogenous expression of VEGF-A, FGF-2, IL-6, IL-10, TNFα, TIMP-1, MMP-9, Hsp47, NF-κB, cleaved Caspase-9, β-Actin, GAPDH and activating phosphorylation of Akt, STAT3, PLC-γ, eNOS, Src, FAK, p38 MAPK and ERK1/2 proteins were measured by Western Blotting in homogenates of proximal, middle and distal segments of the flaps to reflect the pro-angiogenic, inflammatory, anti-apoptotic, stress, motogenic and mitogenic cellular responses. The middle and distal segments were less prone to necrosis in control than in alcohol-fed animals that, in turn, expressed significantly lower levels of activated Akt, STAT3 and p-ERK. This data implies that chronic alcohol consumption leads to flap failure by impairing multiple signaling pathways whose cross-talk is essential for cell survival and expedient wound healing.