Abstract
We sought to determine the effect of ischemic preconditioning (IPC) and hirudotherapy (leech therapy) on cutaneous pedicle flaps after they underwent prolonged ischemia (global ischemia) in a mouse model. Twenty cutaneous pedicle flaps were elevated in 20 mice, and the animals were randomized into four groups: sham, control, IPC and leech (5 flaps in each group). Except in the sham group, all flaps were subjected to global ischemia for 5 h via pedicle clamping. The control group did not receive any treatment before or after global ischemia. In the IPC group, global ischemia was preceded by three 10-min episodes of ischemia, each followed by 10 min of reperfusion. In the leech therapy group, after global ischemia, hirudotherapy was performed. Flap survival area and histopathological changes were evaluated on the 10th day after surgery. Flap survival areas were significantly higher in both the IPC and leech groups than in the control group and were significantly higher in the leech group than in the IPC group (p < 0.05). In conclusion IPC and hirudotherapy had definite effects on the survival area of cutaneous pedicle flaps that underwent prolonged ischemia in a mouse model.
No Level Assigned
This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.
Similar content being viewed by others
References
Papanastasiou S, Estdale SE, Homer-Vanniasinkam S, Mathie RT (1999) Protective effect of preconditioning and adenosine pretreatment in experimental skeletal muscle reperfusion injury. Br J Surg 86:916–922
Erdmann D, Sweis R, Wong MS, Niklason LE, du Laney TV, Levin LS, Klitzman B, Olbrich KC (2003) Vascular endothelial growth factor expression in pig latissimus dorsi myocutaneous flaps after ischemia reperfusion injury. Plast Reconstr Surg 111:775–780
Marian CF, Jiga LP, Ionac M (2005) Ischemic preconditioning of free muscle flaps: an experimental study. Microsurgery 25:524–531
Wang H, Li Z, Liu X (2008) Effects of various protocols of ischemic preconditioning on rat tram flaps. Microsurgery 28(1):37–43
Zahir TM, Zahir KS, Syed SA, Restifo RJ, Thomson JG (1998) Ischemic preconditioning of musculocutaneous flaps: effects of ischemia cycle length and number of cycles. Ann Plast Surg 40(4):430–435
Yang X, Cohen MV, Downey JM (2010) Mechanism of cardioprotection by early ischemic preconditioning. Cardiovasc Drugs Ther 24(3):225–234
Hjortdal VE, Sinclair T, Kerrigan C, Solymoss S (1994) Arterial ischemia in skin flaps: microcirculatory intravascular thrombosis. Plast Reconstr Surg 93(2):375–385
Yingxin G, Guoqian Y, Jiaquan L, Han X (2013) Effects of natural and recombinant hirudin on VEGF expression and random skin flap survival in a venous congested rat model. Int Surg 98:82–87
Lecoq JP, Senard M, Hartstein GM, Lamy M, Heymans O (2006) Thromboprophylaxis in microsurgery. Acta Chir Belg 106:158–164
Nowak G, Schrör K (2007) Hirudin—the long and stony way from an anticoagulant peptide in the saliva of medicinal leech to a recombinant drug and beyond. A historical piece. Thromb Haemost 98:116–119
Koch AA, Olsen SM, Moore EJ (2012) Use of the medicinal leech for salvage of venous congested microvascular free flaps of the head and neck. Am J Otolaryngol Head Neck Med Surg 33(1):26–30
Weinfeld AB, Yuksel E, Boutros S, Gura DH, Akyurek M, Friedman JD (2000) Clinical and scientific considerations in leech therapy for the management of acute venous congestion: an updated review. Ann Plast Surg 45:207–212
Widgerow AD (2014) Ischemia-Reperfusion injury: influencing the microcirculatory and cellular environment. Ann Plast Surg 72(2):253–260
Besse S, Bulteau AL, Boucher F, Riou B, Swynghedauw B, de Leiris J (2006) Antioxidant treatment prevents cardiac protein oxidation after ischemia-reperfusion and improves myocardial function and coronary perfusion in senescent hearts. J Physiol Pharmacol 57(4):541–552
Moore-Olufemi SD, Kozar RA, Moore FA, Sato N, Hassoun HT, Cox CS Jr, Kone BC (2005) Ischemic preconditioning protects against gut dysfunction and mucosal injury after ischemia/reperfusion injury. Shock 23(3):258–263
Avci G, Kadioglu H, Sehirli AO, Bozkurt S, Guclu O, Arslan E, Muratli SK (2012) Curcumin protects against ischemia/reperfusion injury in rat skeletal muscle. J Surg Res 172:39–46
Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136
Taha MO, Miranda-Ferreira R, Chang ACR, Rodrigues AM, Fonseca IS, Toral LB, Cardoso MR, Simões MJ, Oliveira-Junior IS, Monteiro HP, Fagundes DJ, Taha NSA, Caricati-Neto A (2012) Effect of ischemic preconditioning on injuries caused by ischemia and reperfusion in rat intestine. Transplant Proc 44(8):2304–2308
Chen X, Liu X, Wan X, Wu Y, Chen Y et al (2009) Ischemic preconditioning attenuates renal ischemia-reperfusion injury by inhibiting activation of IKKbeta and inflammatory response. Am J Nephrol 30:287–294
Shah AA, Arias JE, Thomson JG (2009) The effect of ischemic preconditioning on secondary ischemia in myocutaneous flaps. J Reconstr Microsurg 25(9):527–531
Steiger HJ, Hänggi D (2007) Ischemic preconditioning of the brain, mechanisms and applications. Acta Neurochir 149:1–10
Clavien PA, Yadav S, Sindram D, Bentley RC (2000) Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans. Ann Surg 232:155–162
Yan S, Jin LM, Liu YX, Zhou L, Xie HY, Zheng SS (2010) Outcomes and mechanisms of ischemic preconditioning in liver transplantation. Hepatobiliary Pancreat Dis Int 9(4):346–354
Perez-Pinzon MA (2007) Mechanisms of neuroprotection during ischemic preconditioning: lessons from anoxic tolerance. Comp Biochem Physiol A 147:291–299
Zahir KS, Syed SA, Zink JR, Restifo RJ, Thomson JG (1998) Ischemic preconditioning improves the survival of skin and myocutaneous flaps in a rat model. Plast Reconstr Surg 102(1):140–150
Matsumura H, Yoshizawa N, Watanabe K, Vedder NB (2001) Preconditioning of the distal portion of a rat random-pattern skin flap. Br J Plast Surg 54(1):58–61
Cleveland JC Jr, Meldrum DR, Rowland RT, Banerjee A, Harken AH (1997) Preconditioning and hypothermic cardioplegia protect human heart equally against ischemia. Ann Thorac Surg 63:147–152
Wall TM, Sheehy R, Hartman JC (1994) Role of bradykinin in myocardial preconditioning. J Pharmacol Exp Ther 270:681–689
Schultz JE, Rose E, Yao Z, Gross GJ (1995) Evidence for involvement of opioid receptors in ischemic preconditioning in rat hearts. Am J Physiol 268:H2157–H2161
Goto M, Liu Y, Yang XM et al (1995) Role of bradykinin in protection of ischemic preconditioning in rabbit hearts. Circ Res 77:611–621
Cohen MV, Yang XM, Liu GS et al (2001) Acetylcholine, bradykinin, opioids, and phenylephrine, but not adenosine, trigger preconditioning by generating free radicals and opening mitochondrial KATP channels. Circ Res 89:273–278
Weinfeld AB, Yuksel E, Boutros S, Gura DH, Akyurek M, Friedman JD (2000) Clinical and scientific considerations in leech therapy for the management of acute venous congestion: an updated review. Ann Plast Surg 45:207–212
Lauche R, Cramer H, Langhorst J, Dobos G (2014) A systematic review and meta- analysis of medical leech therapy for osteoarthritis of the knee. Clin J Pain 30(1):63–72
Michalsen A, Klotz S, Lüdtke R, Moebus S, Spahn G, Dobos GJ (2003) Effectiveness of leech therapy in osteoarthritis of the knee: a randomized, controlled trial. Ann Intern Med 139(9):724–730
Bäcker M, Lüdtke R, Afra D, Cesur O, Langhorst J, Fink M, Bachmann J, Dobos GJ, Michalsen A (2011) Effectiveness of leech therapy in chronic lateral epicondylitis: a randomized controlled trial. Clin J Pain 27(5):442–447
Paruzel M, Jablecki J, Domanasiewicz A, Kaczmarzyk L (2007) Application of leeches in treatment of microcirculation disturbances of replanted fingers: a preliminary report. Pol Prz Chir 79(8):548–554
Chepeha DB, Nussenbaum B, Bradford CR, Teknos TN (2002) Leech therapy for patients with surgically unsalvageable venous obstruction after revascularized free tissue transfer. Arch Otolaryngol Head Neck Surg 128(8):960–965
Nguyen MQ, Crosby MA, Skoracki RJ, Hanasono MM (2012) Outcomes of flap salvage with medicinal leech therapy. Microsurgery 32(5):351–357
Darabi DK, Mirghazanfari SM, Gohari MK, Hejazi S (2014) The effect of leech therapy on linear incisional skin wound healing in male rats. J Acupunct Meridian Stud 7(4):194–201
Land WG (2005) The role of postischemic reperfusion injury and other nonantigen-dependent inflammatory pathways in transplantation. Transplantation 79(5):505–514
Jaeschke H, Farhood A (1991) Neutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in rat liver. Am J Physiol 260(3 Pt 1):G355–G362
Behrend M (2000) Immune-adhesion molecules in the prevention of allograft rejection and reperfusion injury. Expert Opin Investig Drugs 9:789–805
Prada FS, Arrunategui G, Alves MC, Ferreira MC, Zumiotti AV (2002) Effect of allopurinol, superoxide-dismutase, and hyperbaric oxygen on flap survival. Microsurgery 22(8):352–360
Russell JA, Conforti ML, Connor NP, Hartig GK (2006) Cutaneous tissue flap viability following partial venous obstruction. Plast Reconstr Surg 117(7):2259–2266
Birk-Sørensen L, Fuglsang J, Sørensen HB, Kerrigan CL, Petersen LC, Ravn HB, Hjortdal VE (1999) Aprotinin attenuates platelet accumulation in ischaemia-reperfusion-injured porcine skeletal muscle. Blood Coagul Fibrinolysis 10(4):157–165
Hjortdal VE, Sinclair T, Kerrigan CL, Solymoss S (1994) Venous ischemia in skin flaps: microcirculatory intravascular thrombosis. Plast Reconstr Surg 93(2):366–375
Guo-Qian Y, Gang W, Zhi-Yong S (2012) Investigation on the microcirculation effect of local application of natural hirudin on porcine random skin flap venous congestion. Cell Biochem Biophys 62(1):141–146
Livaoğlu M, Kerimoğlu S, Sönmez B, Livaoğlu A, Karaçal N (2010) The effect of Hirudoid on random skin-flap survival in rats. J Plast Reconstr Aesthet Surg 63(6):1047–1051
Guo YG, Yin GQ, Li JQ, Xiao HX (2011) Effects of natural and recombinant hirudin on superoxide dismutase, malondialdehyde and endothelin levels in a random pattern skin flap model. J Hand Surg 37(1):42–49
Conflict of interest
The authors have no conflicts of interest to disclose.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Moosavian, H.R., Mirghazanfari, S.M. & Moghaddam, K.G. Effect of Ischemia Preconditioning and Leech Therapy on Cutaneous Pedicle Flaps Subjected to Prolonged Ischemia in a Mouse Model. Aesth Plast Surg 38, 1024–1029 (2014). https://doi.org/10.1007/s00266-014-0399-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00266-014-0399-y