title: Ischemic preconditioning improves the survival of skin and myocutaneous flaps in a rat model.
abstract: Inadequate blood supply of pedicle flaps results in partial necrosis, and prolonged ischemia during free-tissue transfer can result in partial or complete flap necrosis. Recent research in the field of cardiovascular surgery has shown that ischemic preconditioning (repeated brief episodes of coronary artery occlusion followed by reperfusion) improves myocardial muscle survival when the heart is subsequently subjected to prolonged ischemia. Preconditioning of skin or myocutaneous flaps as either pedicle or free flap models has never been studied. The goal of this investigation was to measure the effect of ischemic preconditioning on myocutaneous and skin flap survival areas and total necrosis rates after variable periods of global ischemia. In 220 rats, 100 transverse rectus abdominis myocutaneous flaps and 120 dorsal cutaneous flaps were randomized into treatment and control groups. The treatment flaps underwent preconditioning by three cycles of 10 minutes of pedicle clamping followed by 10 minutes of reperfusion for a total preconditioning period of 1 hour. The control flaps were perfused without clamping for 1 hour. Both control and treatment flaps then underwent global ischemia for 0, 2, 4, 6, 10, or 14 hours by pedicle clamping. Flap survival area was measured on the fifth postoperative day. Statistical analysis was performed with analysis of variance, student's t tests, and probit analysis. Preconditioning improved survival areas of pedicle myocutaneous flaps (0-hour group) from 47 +/- 16 percent (mean percent area surviving +/- SD) to 63 +/- 5 percent. This difference was statistically significant (t test, p < 0.04). There was no statistically significant improvement in pedicle skin flap survival. For free flap models (flaps undergoing global ischemia), preconditioning increased the survival areas of skin and myocutaneous flaps (analysis of variance, p < 10(-5)). For the skin flap model, statistical significance of the survival area difference was reached at 6, 10, and 14 hours of ischemia (t test, p < 10(-4)). The magnitude of this effect was higher in the myocutaneous flap model and reached statistical significance at 2, 4, 6, and 10 hours of ischemia (p < 10(-3)). Preconditioned flap survival areas were increased by two to five times that of non-preconditioned flaps at these ischemia times. Preconditioning lowered total necrosis rates at all ischemia times for both flap models. The critical ischemia time when 50 percent of skin flaps became totally necrotic (CIT50) improved from 6.9 to 12.4 hours by preconditioning. Similarly, preconditioning improved the CIT50 of myocutaneous flaps from 3.6 to 9.2 hours. For the first time, statistically significant improvements of partial necrosis areas and total necrosis rates have been demonstrated through intraoperative ischemic preconditioning of skin and myocutaneous flaps. In clinical practice, application of this technique may lead to improved survival during pedicled or free transfer of myocutaneous flaps and free transfer of skin flaps.
authors.affiliation: Section of Plastic Surgery at Yale University School of Medicine, New Haven, Conn 06520-8041, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Zahir
authors.forename: S A
authors.initials: SA
authors.lastname: Syed
authors.forename: J R
authors.initials: JR
authors.lastname: Zink
authors.forename: R J
authors.initials: RJ
authors.lastname: Restifo
authors.forename: J G
authors.initials: JG
authors.lastname: Thomson
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003250:Constriction; D004195:Disease Models, Animal; D006085:Graft Survival; D007430:Intraoperative Care; D019194:Ischemic Preconditioning / Q000379:methods; D008297:Male; D009336:Necrosis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017568:Rectus Abdominis / Q000098:blood supply* / Q000473:pathology / Q000637:transplantation; D015424:Reperfusion; D012867:Skin / Q000098:blood supply* / Q000473:pathology; D016038:Skin Transplantation / Q000379:methods* / Q000473:pathology; D013524:Surgical Flaps / Q000098:blood supply* / Q000473:pathology; D013997:Time Factors