二氯乙酸可减轻大鼠腹直肌横形肌皮瓣模型中的组织坏死。

Dichloroacetate reduces tissue necrosis in a rat transverse rectus abdominis musculocutaneous flap model.

作者信息

Tyner Tim R, Tong Winnie, Donovan Kelli, McDonald Travis, Sian Kenty, Yamaguchi Kent T

机构信息

Department of Surgery, University Medical Center, Veterans Administration Medical Center, University of California San Francisco-Fresno Medical Education Program, CA 93702, USA.

出版信息

Ann Plast Surg. 2006 Mar;56(3):320-6. doi: 10.1097/01.sap.0000194549.39544.cd.

DOI:10.1097/01.sap.0000194549.39544.cd

PMID:16508366

Abstract

OBJECTIVE

Ischemia-related complications may occur during postmastectomy transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction. The aim of our study was to investigate whether necrosis of susceptible flap regions could be reduced by dichloroacetate (DCA)-induced stimulation of oxidative metabolism in hypoxic tissue.

METHODS

The study was a randomized control trial using male Sprague-Dawley rats. A pedicled TRAM flap based upon the right inferior epigastric artery was elevated and reapproximated. Animals were randomly assigned to 1 of 5 treatment groups (n = 6). Group I received no DCA; groups II through V were administered 75 mg/kg DCA orally 24 hours preoperative; in addition, groups II through IV received 75 mg/kg/d DCA orally postoperative for 4 days; group III also received 75 mg/kg DCA (IP) intraoperatively; groups IV and V were given 15 mg/kg/d DCA orally for 6 days before the 24-hour preoperative treatment. Four days postsurgery, skin paddles were photographed and assessed for viability. Underlying TRAM muscle was biopsied for histologic analysis. Blood lactate levels were measured at pre- and postoperative time points. The mean percentages of viable skin paddle were as follows: 32.0%+/- 4.0% (group I), 68.1% +/- 6.2% (group II), 84.3% +/- 5.9% (group III), 92.8% +/- 2.0% (group IV), 82.6% +/- 5.8% (group V).

RESULTS

Statistically significant differences were found in all experimental (DCA) groups relative to the controls (P < 0.01). Group IV (6-day DCA preconditioning, plus 24-hour preoperative and 4-day postoperative treatment) displayed the greatest improvement in flap viability, significantly better than other DCA groups (P < 0.01). Group IV also had significantly lower serum lactate levels than controls (P < 0.05). Histologic examination of muscle biopsies revealed reductions in inflammation and necrosis correlating with DCA treatment and skin paddle survival.

CONCLUSIONS

This study indicates that DCA may provide a useful pharmacologic tool for reducing ischemia-related necrosis in TRAM flaps.

摘要

目的

乳房切除术后横行腹直肌肌皮瓣（TRAM瓣）重建过程中可能会出现缺血相关并发症。本研究的目的是调查二氯乙酸（DCA）诱导缺氧组织中的氧化代谢是否能减少易损皮瓣区域的坏死。

方法

本研究是一项使用雄性Sprague-Dawley大鼠的随机对照试验。掀起并重新贴合基于右下腹壁动脉的带蒂TRAM瓣。将动物随机分配到5个治疗组之一（n = 6）。第一组未接受DCA；第二组至第五组在术前24小时口服75 mg/kg DCA；此外，第二组至第四组在术后口服75 mg/kg/d DCA，持续4天；第三组还在术中接受75 mg/kg DCA（腹腔注射）；第四组和第五组在术前24小时治疗前6天口服15 mg/kg/d DCA，持续6天。术后4天，拍摄皮瓣照片并评估其活力。对下方的TRAM肌进行活检以进行组织学分析。在术前和术后时间点测量血乳酸水平。存活皮瓣的平均百分比分别为：32.0%±4.0%（第一组），68.1%±6.2%（第二组），84.3%±5.9%（第三组），92.8%±2.0%（第四组），82.6%±5.8%（第五组）。

结果

与对照组相比，所有实验组（DCA组）均存在统计学上的显著差异（P < 0.01）。第四组（6天DCA预处理，加术前24小时和术后4天治疗）皮瓣活力改善最大，显著优于其他DCA组（P < 0.01）。第四组血清乳酸水平也显著低于对照组（P < 0.05）。肌肉活检的组织学检查显示，炎症和坏死的减少与DCA治疗及皮瓣存活相关。