Acute Remote Preconditioning Augments Random Skin Flap Survival, But Not Recipient-Bed Isolated Flaps In Rats

摘要

This study proposes that acute remote preconditioning (ARIP) can effectively enhance random skin flap survival.The study was a randomized controlled trial using male sprague-Dawley rats as subjects. For acute remote preconditioning, left hindlimb ischemia was achieved by clamping the femoral artery and vein.After 1 hour's ischemia, the limb reperfusion was done for 30 minutes. Then, a 3- by 9- cm dorsal caudal-based, random pattern skin flap was elevated and reaproximated for flap survival studies. Thirty rats were divided into three groups of 10 rats each. The first group had only the flap raised, while the second and third groups had acute remote preconditioning protocol before the flap elevation. In the third group, a silicone sheet was inserted beneath the flap in order to prevent neovascularisation from the bed. The amount of flap necrosis was measured on the seventh postoperative day. ARIP (acute remote ischemic preconditioning) group had the most improved skin flap survival rate, and the flap survival rates between the ARIP+silicone sheet and control groups was not statistically different (p>0.05). These findings indicate that remote ischemic precontioning enhances random skin flap survival, when it is performed just before the flap harvest and the isolation of recipient bed abolishes this ameloriating effect. Introduction Allow for protection of briefly ischemic tissues against the harmful effects of subsequent prolonged ischemia is a phenomennon called as Ischemic Preconditioning (IP). Adaptational responses to Ischemia/Reperfusion (I/R) injury have been demonstrated in different tissue types.There are two distinct types of protection afforded by this adaptational reponse, i.e. acute and delayed preconditioning. The factors that initiate the acute and delayed preconditioning responses appear to be similiar. However, the protective effects of acute preconditioning are protein synthesis independent, while the effects of delayed preconditioning require protein synthesis (1). The inflammatory mediators released as a consequence of reperfusion also appear to activate endothelial cells in remote organs that are not exposed to the initial ischemic insult.This second phenomennon is called as acute remote ischemic preconditioning (ARIP). ARIP has been reported to be succesful for organs such as the heart, kidney and liver (1). Verdouw et al. were the first to report a real remote ischemic preconditioning of the heart by mesenteric artery occlusion in a rat model (2). The protective influence of limb ischemia on myocardial infarction was reported by Birnbaum et al. and Oxman et al. (3,4). Kuntscher et al. showed that ischemic preconditioning and enhancement of flap survival can be achieved not only by preclamping of the flap pedicle, but also by induction of an ischemia/reperfusion event in a body area distant from the flap before harvest (5). The exact mechanism of classic and remote preconditioning has not yet been determined. We aimed to evaluate the effects of ARIP on a different random pattern skin flap model with a different model of limb I/R protocol and the impact of recipient-bed isolation on skin flap survival with remote protection by ischemic preconditioning. Materials And Methods Thirty male Wistar rats weighing between 230 and 335 g were divided into three experimental groups. In the control group (n = 10), caudal-based random skin flaps in adiameter of 3x9 cm were elevated and resutured the original bed with continous subcutaneous 4/0 prolene sutures.In the ARIP group, the same random skin flap elevated just after the completion of 1 hour's ischemia and 30 minutes reperfusion of the left hindlimb.In the ARIP+silicone sheet group, the flap was thereafter sutured back and placed onto a silicone sheet to prevent neovascularization from the wound bed.The flap site was prepared by shaving with electric hair clippers and betadine.Ischemia of the left hindlimb was induced by clamping left femoral artery and vein using A