Abstract

Background: Numerous pre-clinical studies have demonstrated that pre-conditioning before surgery with various forms of dietary restriction enhances the surgical stress response leading to improved outcomes. However the effect of restricting proteins or amino acids for seven days prior to surgery on a healing surgical wound is currently unknown. Therefore using a using an established murine wound healing model we hypothesized that pre-operative protein restriction (PR) or methionine restriction (MR) would not impair wound healing. Approach & Results: To asses wound healing potential a Mcfarlane wound healing model was employed where a pedicle flap measuring 2.5 x 1.25cm with a silicone sheet inferior to flap to prevent angiogenesis from bellow on the dorsum of the mouse was performed. Dietary interventions included 7 days of either an iso-caloric protein restricted (90% carb., 10% fat, 0% protein) diet or 3 weeks of an methionine restricted (76% carb., 10% fat, 14% protein) diet before surgery and resumed a complete (72% carb., 10% fat, 18% protein) diet post op. Daily photographs of the wound were taken and necrotic area was calculated. PR mice revealed a trend towards accelerated wound healing, with no difference in percentage of viable skin 7 days after surgery (Fig. A). Also, daily laser Doppler imaging was performed to assess for flap perfusion and viability (Fig. B,E). MR mice displayed accelerated wound healing 3 days after surgery (Fig. C, p<0.05) compared to controls while after 7 days, as with PR mice, no difference in percentage viable skin was observed (Fig. D). Conclusion: Reducing/removing protein intake or eliminating single amino acids prior to surgery in pre-clinical models has shown to protect against surgical stress. Here we show that brief dietary-manipulations stand as simple strategies toward improving the host response to surgical injury and do not inhibit or impair wound healing in mice, thereby further enhancing clinical applicability.

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