Abstract
BACKGROUND: Alcohol intoxication occurs in nearly half of all trauma patients and increases the morbidity, mortality, and healing complications of these patients. Prior studies in our laboratory and elsewhere have demonstrated impairments in re-epithelialization, angiogenesis, and inflammation in wounds following acute ethanol exposure. Clinically, acute ethanol exposure has been shown to cause an increased breakdown of wounds. To date, the mechanisms by which acute ethanol exposure modifies wound strength have received little experimental attention. METHODS: To examine how ethanol influences functions critical to the development of wound strength, the effect of ethanol exposure on fibroblast proliferation and extracellular matrix production was examined. Normal human dermal fibroblasts (NHDF) were exposed to ethanol (100 mg/dl) and then examined for proliferative capacity and mRNA production of collagen I, collagen III, and lysyl oxidase (LOX). In in vivo studies, the wound breaking strength, LOX activity, collagen, and hyaluronic acid (HA) contents of wounds of ethanol-exposed (100 mg/dl) mice were examined. RESULTS: At 24, 48, and 72 hours after acute ethanol exposure (8 hours duration), NHDF displayed a significant impairment in proliferative capacity (up to 50% at 24 hours p < 0.001). After ethanol exposure, NHDF produced less collagen I and LOX mRNA, but more collagen III mRNA than control fibroblasts (p < 0.05). Ethanol exposure in vivo caused a reduction in wound breaking strength of up to 40% when compared to control mice (p < 0.01). LOX activity, collagen, and HA contents in the wounds of ethanol-exposed mice were significantly reduced (p < 0.01). CONCLUSIONS: These studies reveal that a single exposure to ethanol prior to injury can cause a significant decrease in wound breaking strength. Our studies suggest that ethanol directly impairs fibroblast function, leading to decreased collagen production. The results provide a possible explanation for how acute ethanol exposure might increase in wound complications and wound failure.