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Peri-Operative Administration of Resveratrol Did Not Hinder Abdominal or Gastric Wound Healing in a Murine Model
Xiaohong Yan*1, Thomas Gardner2, Virginia Gillespie3, Linda Njoh1, Chandana H. Mudiyanselage1, Geoffrey Bellini1, Elie Sutton1, Richard L. Whelan1
1Surgery, Mount Sinai Roosevelt Hospital, New York, NY; 2Orthopedic Surgery, Columbia University, New York, NY; 3Comparative Medicine and Surgery, Ichan School of Medicine at Mount Sinai, New York, NY
Introduction: Colorectal resection (CRR) for cancer is associated with persistent transient proangiogenic plasma protein changes. Plasma from the 2nd and 3rd weeks after CRR stimulates endothelial cell proliferation and migration in vitro when compared to preoperative plasma results. These changes may promote tumor angiogenesis in residual cancer deposits early after CRR. Thus, it is logical to give anti-cancer agents perioperatively; for safe use in this period, in addition to having anti-cancer effects, candidate agents must not impair wound healing. Resveratrol, a phenol found in the skin of red grapes, has been shown to have anti-cancer effects in vitro and in rodents. Although studies regarding resveratrol’s anti-cancer effects have been done little is known about this agent’s impact on wound healing. This murine study’s purpose was to assess this agent’s effects on wound healing.
Methods: Forty 8-week old female Balb/cJ mice were randomized into 2 groups and given, for 7 days prior to surgery, via gavage: 1) resveratrol in water (150mg/Kg) or 2) water alone (equal volume). All mice underwent sham laparotomy and gastrotomy. Gastric wounds were closed with 6-0 polypropylene sutures and abdominal wounds with full thickness 4-0 nylon sutures. Drug or placebo via gavage was resumed on postoperative day (POD) 1. Ten mice from each group were sacrificed on POD 7 and the other 10 on POD 14. Abdominal pelts were harvested and cut into equal width strips after which the following tests were done: absorbable collagen content analysis, tensiometry, and histologic study (7 parameters). Stomachs were excised and bursting pressure determined ex vivo. The Wilcoxon/Kruskal-Wallis tests were used to assess the results.
Results: Abdominal wound. Collagen content: no differences were found between groups on POD7 (control 0.239mg/g vs. drug 0.259mg/g, p=0.982) or POD14 (0.225mg/g vs. 0.276mg/g, p=0.816). Histology: Similar results were noted on POD7/14 for all 8 parameters except that on POD7 the drug group had faster epidermal healing (p=0.033) and more fibroblast proliferation (p=0.019).
Tensiometry: No differences were noted in energy needed to break the wound (Energy of Failure-EOF) on POD 7 (EOF 2.215N-mm vs. 2.404N-mm, p=0.853) or POD 14 (5.574N-mm vs. 4.983N-mm, p=0.406). Regarding peak force (PF), on POD 7 no difference was noted (PF 0.710N vs. 0.720N, p=0.762) but on POD 14 the drug group PF was lower (1.106N vs. 0.962N, p=0.049).
Gastric wound. Bursting pressures: No differences were noted on POD7 (100.4mmHg vs. 102.3mmHg, p=0.545) or POD14 (139.8mmHg vs. 116.3mmHg, p=0.290).
Conclusion: At all but 1 timepoint (total 12 parameters and 24 timepoints), the drug group healing results were similar to control group results. Further study is needed, however, these results suggest resveratrol can be safely taken perioperatively.
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