title: Dichloroacetate reduces tissue necrosis in a rat transverse rectus abdominis musculocutaneous flap model.
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.
authors.affiliation: Department of Surgery, University Medical Center, Veterans Administration Medical Center, University of California San Francisco-Fresno Medical Education Program, CA 93702, USA.
authors.forename: Tim R
authors.initials: TR
authors.lastname: Tyner
authors.forename: Winnie
authors.initials: W
authors.lastname: Tong
authors.forename: Kelli
authors.initials: K
authors.lastname: Donovan
authors.forename: Travis
authors.initials: T
authors.lastname: McDonald
authors.forename: Kenty
authors.initials: K
authors.lastname: Sian
authors.forename: Kent T
authors.initials: KT
authors.lastname: Yamaguchi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D008297:Male; D009336:Necrosis / Q000517:prevention & control; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017568:Rectus Abdominis / Q000098:blood supply / Q000473:pathology* / Q000637:transplantation*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013524:Surgical Flaps / Q000098:blood supply* / Q000473:pathology
chemical_list: D003999:Dichloroacetic Acid