An old dream revitalised: preconditioning strategies to protect surgical flaps from critical ischaemia and ischaemia-reperfusion injury

Journal of Plastic, Reconstructive and Aesthetic Surgery

Volumn 61, Issue 5, 2008, Pages 503-511

  Harder, Y ^a,b   Amon, M ^a   Laschke, M W ^a   Schramm, R ^a   Rucker M ^a   Wettstein, R ^b   Bastiaanse, J ^c   Frick, A ^d   Machens, H G ^e   Kuntscher M ^f   Germann, G ^g   Vollmar, B ^h   Erni, D ⁱ   Menger, M D ^a  

^a SAARLAND UNIVERSITY   (Germany)

^b UNIVERSITY OF GENEVA   (Switzerland)

^c MAASTRICHT UNIVERSITY   (Netherlands)

^d UNIVERSITY OF MUNICH   (Germany)

^e UNIVERSITY HOSPITAL SCHLESWIG HOLSTEIN   (Germany)

^f Burn Center   (Germany)

^g UNIVERSITY OF HEIDELBERG   (Germany)

^h UNIVERSITY OF ROSTOCK   (Germany)

ⁱ UNIVERSITY OF BERN   (Switzerland)

Author keywords

Critical ischaemia; Flap; Ischaemia reperfusion; Ischaemic preconditioning; Ischaemic tolerance; Surgical delay

Indexed keywords

ADENOSINE; ANGIOTROPIN; BASIC FIBROBLAST GROWTH FACTOR; CYCLOSPORIN A; DEXAMETHASONE; DEXTRAN; ERYTHROPOIETIN; GROWTH FACTOR; HEPARIN; INDOMETACIN; ISOXSUPRINE; LEUKOTRIENE B4 RECEPTOR ANTAGONIST; LIPOXYGENASE INHIBITOR; PHOSPHORYL LIPID A; PLATELET DERIVED GROWTH FACTOR; PROSTACYCLIN; SPERMINE; TACROLIMUS; THROMBOXANE SYNTHASE INHIBITOR; VASCULOTROPIN; VERAPAMIL; XANTHINE;

ANTIINFLAMMATORY ACTIVITY; BIOLOGICAL PHENOMENA AND FUNCTIONS CONCERNING ORGAN SYSTEMS; BLOOD FLOW; CELL DAMAGE; CLINICAL PRACTICE; COOLING; GANGRENE; HEATING; HUMAN; ISCHEMIA; ISCHEMIC PRECONDITIONING; LOW DRUG DOSE; MICROCIRCULATION; NONHUMAN; NUTRIENT SUPPLY; OXYGEN SUPPLY; PLASTIC SURGERY; PRIORITY JOURNAL; REPERFUSION INJURY; REVIEW; TISSUE INJURY;

GROWTH SUBSTANCES; HUMANS; HYPERTHERMIA, INDUCED; HYPOTHERMIA, INDUCED; ISCHEMIC PRECONDITIONING; MICROCIRCULATION; REPERFUSION INJURY; SURGICAL FLAPS;

EID: 43049176421     PISSN: 17486815     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bjps.2007.11.032     Document Type: Review

References (141)

1. Khouri R.K., Cooley B.C., Kunselman A.R., et al. A prospective study of microvascular free-flap surgery and outcome. Plast Reconstr Surg 102 (1998) 711-721
2. Moran S.L., Nava G., Behnam A.B., et al. An outcome analysis comparing the thoracodorsal and internal mammary vessels as recipient sites for microvascular breast reconstruction: a prospective study of 100 patients. Plast Reconstr Surg 111 (2003) 1876-1882
3. Nahabedian M.Y., Momen B., and Manson P.N. Factors associated with anastomotic failure after microvascular reconstruction of the breast. Plast Reconstr Surg 114 (2004) 74-82
4. Banic A., Boeckx W., Greulich M., et al. Late results of breast reconstruction with free TRAM flaps: a prospective multicentric study. Plast Reconstr Surg 95 (1995) 1195-1204 [discussion: 205-6]
5. Wei F.C., Celik N., Chen H.C., et al. Combined anterolateral thigh flap and vascularized fibula osteoseptocutaneous flap in reconstruction of extensive composite mandibular defects. Plast Reconstr Surg 109 (2002) 45-52
6. Moran S.L., and Serletti J.M. Outcome comparison between free and pedicled TRAM flap breast reconstruction in the obese patient. Plast Reconstr Surg 108 (2001) 1954-1960 [discussion: 61-2]
7. Tanaka N., Yamaguchi A., Ogi K., et al. Sternocleidomastoid myocutaneous flap for intraoral reconstruction after resection of oral squamous cell carcinoma. J Oral Maxillofac Surg 61 (2003) 1179-1183
8. Harder Y., Amon M., Georgi M., et al. Evolution of a "falx lunatica" in demarcation of critically ischemic myocutaneous tissue. Am J Physiol Heart Circ Physiol 288 (2005) H1224-H1232
9. Carroll C.M., Carroll S.M., Overgoor M.L., et al. Acute ischemic preconditioning of skeletal muscle prior to flap elevation augments muscle-flap survival. Plast Reconstr Surg 100 (1997) 58-65
10. Pang C.Y., Yang R.Z., Neligan P., et al. Vascular effects and mechanism of action of endothelin-1 in isolated perfused pig skin. J Appl Physiol 79 (1995) 2106-2113
11. Im M.J., Manson P.N., Bulkley G.B., et al. Effects of superoxide dismutase and allopurinol on the survival of acute island skin flaps. Ann Surg 201 (1985) 357-359
12. Manson P.N., Anthenelli R.M., Im M.J., et al. The role of oxygen-free radicals in ischemic tissue injury in island skin flaps. Ann Surg 198 (1983) 87-90
13. Manson P.N., Narayan K.K., Im M.J., et al. Improved survival in free skin flap transfers in rats. Surgery 99 (1986) 211-215
14. Eppihimer M.J., and Granger D.N. Ischemia/reperfusion-induced leukocyte-endothelial interactions in postcapillary venules. Shock 8 (1997) 16-25
15. Menger M.D., Pelikan S., Steiner D., et al. Microvascular ischemia-reperfusion injury in striated muscle: significance of "reflow paradox". Am J Physiol 263 (1992) H1901-H1906
16. Menger M.D., and Vollmar B. Adhesion molecules as determinants of disease: from molecular biology to surgical research. Br J Surg 83 (1996) 588-601
17. Murry C.E., Jennings R.B., and Reimer K.A. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74 (1986) 1124-1136
18. Glazier S.S., O'Rourke D.M., Graham D.I., et al. Induction of ischemic tolerance following brief focal ischemia in rat brain. J Cereb Blood Flow Metab 14 (1994) 545-553
19. Hotter G., Closa D., Prados M., et al. Intestinal preconditioning is mediated by a transient increase in nitric oxide. Biochem Biophys Res Commun 222 (1996) 27-32
20. Pang C.Y., Yang R.Z., Zhong A., et al. Acute ischaemic preconditioning protects against skeletal muscle infarction in the pig. Cardiovasc Res 29 (1995) 782-788
21. Peralta C., Closa D., Hotter G., et al. Liver ischemic preconditioning is mediated by the inhibitory action of nitric oxide on endothelin. Biochem Biophys Res Commun 229 (1996) 264-270
22. Du Z.Y., Hicks M., Winlaw D., et al. Ischemic preconditioning enhances donor lung preservation in the rat. J Heart Lung Transplant 15 (1996) 1258-1267
23. Turman M.A., and Bates C.M. Susceptibility of human proximal tubular cells to hypoxia: effect of hypoxic preconditioning and comparison to glomerular cells. Ren Fail 19 (1997) 47-60
24. Yamashita N., Hoshida S., Nishida M., et al. Time course of tolerance to ischemia-reperfusion injury and induction of heat shock protein 72 by heat stress in the rat heart. J Mol Cell Cardiol 29 (1997) 1815-1821
25. Cleveland Jr. J.C., Meldrum D.R., Rowland R.T., et al. Preconditioning and hypothermic cardioplegia protect human heart equally against ischemia. Ann Thorac Surg 63 (1997) 147-152
26. Riepe M.W., Esclaire F., Kasischke K., et al. Increased hypoxic tolerance by chemical inhibition of oxidative phosphorylation: "chemical preconditioning". J Cereb Blood Flow Metab 17 (1997) 257-264
27. Friehs I., Moran A.M., Stamm C., et al. Promoting angiogenesis protects severely hypertrophied hearts from ischemic injury. Ann Thorac Surg 77 (2004) 2004-2010 [discussion: 11]
28. De Maio A., Beck S.C., and Buchman T.G. Induction of translational thermotolerance in liver of thermally stressed rats. Eur J Biochem 218 (1993) 413-420
29. Nayeem M.A., Elliott G.T., Shah M.R., et al. Monophosphoryl lipid A protects adult rat cardiac myocytes with induction of the 72-kD heat shock protein: a cellular model of pharmacologic preconditioning. J Mol Cell Cardiol 29 (1997) 2305-2310
30. Wada T., Kondoh T., and Tamaki N. Ischemic "cross" tolerance in hypoxic ischemia of immature rat brain. Brain Res 847 (1999) 299-307
31. Reinisch J.F. The pathophysiology of skin flap circulation. The delay phenomenon. Plast Reconstr Surg 54 (1974) 585-598
32. Aydin M.A., and Mavili M.E. Examining microcirculation improves the angiosome theory in explaining the delay phenomenon in a rabbit model. J Reconstr Microsurg 19 (2003) 187-194
33. Morris S.F., and Taylor G.I. The time sequence of the delay phenomenon: when is a surgical delay effective? An experimental study. Plast Reconstr Surg 95 (1995) 526-533
34. Braithwaite F. Some observations on the vascular channels in tubed pedicles. II. Br J Plast Surg 4 (1951) 28-37
35. McFarlane R.M., Heagy F.C., Radin S., et al. A study of the delay phenomenon in experimental pedicle flaps. Plast Reconstr Surg 35 (1965) 245-262
36. Jonsson K., Hunt T.K., Brennan S.S., et al. Tissue oxygen measurements in delayed skin flaps: a reconsideration of the mechanisms of the delay phenomenon. Plast Reconstr Surg 82 (1988) 328-336
37. Serafin D., Shearin J.C., and Georgiade N.G. The vascularization of free flaps: a clinical and experimental correlation. Plast Reconstr Surg 60 (1977) 233-241
38. Park S.S., Rodeheaver G.T., and Levine P.A. Role of ischemic gradient in neovascularization of interpolated skin flaps. Arch Otolaryngol Head Neck Surg 122 (1996) 886-889
39. Zink J.R., Syed S.A., Zahir K., et al. Transferring vascular territories from one axial pattern flap to another: a comparison of delay procedures. Ann Plast Surg 38 (1997) 385-387
40. Callegari P.R., Taylor G.I., Caddy C.M., et al. An anatomic review of the delay phenomenon: I. Experimental studies. Plast Reconstr Surg 89 (1992) 397-407 [discussion: 17-8]
41. Cederna P.S., Chang P., Pittet-Cuenod B.M., et al. The effect of the delay phenomenon on the vascularity of rabbit abdominal cutaneous island flaps. Plast Reconstr Surg 99 (1997) 183-193
42. Cederna P.S., Chang P., Pittet-Cuenod B.M., et al. The effect of the delay phenomenon on the vascularity of rabbit rectus abdominis muscles. Plast Reconstr Surg 99 (1997) 194-205
43. Hauben D.J., and Zijlstra F.J. Prostacyclin formation in delayed pig flank flaps. Ann Plast Surg 13 (1984) 304-308
44. McDonald W.S., Lo Jr. T.P., Thurmond M., et al. Role of nitric oxide in skin flap delay. Plast Reconstr Surg 113 (2004) 927-931
45. Kubulus D., Roesken F., Amon M., et al. Mechanism of the delay phenomenon: tissue protection is mediated by heme oxygenase-1. Am J Physiol Heart Circ Physiol 287 (2004) H2332-H2340
46. Fan L.K., Wang C., Hansen W., et al. Hsp72 induction: a potential molecular mediator of the delay phenomenon. Ann Plast Surg 44 (2000) 65-71
47. Wong M.S., Erdmann D., Sweis R., et al. Basic fibroblast growth factor expression following surgical delay of rat transverse rectus abdominis myocutaneous flaps. Plast Reconstr Surg 113 (2004) 2030-2036
48. Cohen B.E., Harmon C.S., and Phizackerley P.J. Glucose metabolism in experimental skin flaps. Plast Reconstr Surg 71 (1983) 79-86
49. Hoopes J.E., Su C.T., and Im M.J. Enzymatic responses to skin flap elevation following a delay procedure. Plast Reconstr Surg 66 (1980) 369-372
50. Im M.J., Su C.T., and Hoopes J.E. Metabolic adaptations in delayed skin flaps. Glucose utilization and hexokinase activity. Plast Reconstr Surg 64 (1979) 244-248
51. Erdmann D., Sundin B.M., Moquin K.J., et al. Delay in unipedicled TRAM flap reconstruction of the breast: a review of 76 consecutive cases. Plast Reconstr Surg 110 (2002) 762-767
52. Restifo R.J., Ward B.A., Scoutt L.M., et al. Timing, magnitude, and utility of surgical delay in the TRAM flap: II. Clinical studies. Plast Reconstr Surg 99 (1997) 1217-1223
53. Taylor G.I., and Minabe T. The angiosomes of the mammals and other vertebrates. Plast Reconstr Surg 89 (1992) 181-215
54. Scheufler O., Andresen R., Kirsch A., et al. Clinical results of TRAM flap delay by selective embolization of the deep inferior epigastric arteries. Plast Reconstr Surg 105 (2000) 1320-1329
55. Cherry G.W., Austad E., Pasyk K., et al. Increased survival and vascularity of random-pattern skin flaps elevated in controlled, expanded skin. Plast Reconstr Surg 72 (1983) 680-687
56. Kato H., Liu Y., Kogure K., et al. Induction of 27-kDa heat shock protein following cerebral ischemia in a rat model of ischemic tolerance. Brain Res 634 (1994) 235-244
57. Glanemann M., Vollmar B., Nussler A.K., et al. Ischemic preconditioning protects from hepatic ischemia/reperfusion-injury by preservation of microcirculation and mitochondrial redox-state. J Hepatol 38 (2003) 59-66
58. Kume M., Yamamoto Y., Saad S., et al. Ischemic preconditioning of the liver in rats: implications of heat shock protein induction to increase tolerance of ischemia-reperfusion injury. J Lab Clin Med 128 (1996) 251-258
59. Cochrane J., Williams B.T., Banerjee A., et al. Ischemic preconditioning attenuates functional, metabolic, and morphologic injury from ischemic acute renal failure in the rat. Ren Fail 21 (1999) 135-145
60. Mounsey R.A., Pang C.Y., Boyd J.B., et al. Augmentation of skeletal muscle survival in the latissimus dorsi porcine model using acute ischemic preconditioning. J Otolaryngol 21 (1992) 315-320
61. Adanali G., Ozer K., and Siemionow M. Early and late effects of ischemic preconditioning on microcirculation of skeletal muscle flaps. Plast Reconstr Surg 109 (2002) 1344-1351
62. Hopper R.A., Forrest C.R., Xu H., et al. Role and mechanism of PKC in ischemic preconditioning of pig skeletal muscle against infarction. Am J Physiol Regul Integr Comp Physiol 279 (2000) R666-R676
63. Kinnunen I., Laurikainen E., Schrey A., et al. Effect of acute ischemic preconditioning on blood-flow response in the epigastric pedicled rat flap. J Reconstr Microsurg 18 (2002) 61-68
64. Pang C.Y., Neligan P., Zhong A., et al. Effector mechanism of adenosine in acute ischemic preconditioning of skeletal muscle against infarction. Am J Physiol 273 (1997) R887-R895
65. Wang W.Z., Anderson G., Firrell J.C., et al. Ischemic preconditioning versus intermittent reperfusion to improve blood flow to a vascular isolated skeletal muscle flap of rats. J Trauma 45 (1998) 953-959
66. Zahir K.S., Syed S.A., Zink J.R., et al. Ischemic preconditioning improves the survival of skin and myocutaneous flaps in a rat model. Plast Reconstr Surg 102 (1998) 140-150 [discussion: 51-2]
67. Zahir K.S., Syed S.A., Zink J.R., et al. Comparison of the effects of ischemic preconditioning and surgical delay on pedicled musculocutaneous flap survival in a rat model. Ann Plast Surg 40 (1998) 422-428 [discussion: 8-9]
68. Zhang F., Oswald T., Holt J., et al. Regulation of inducible nitric oxide synthase in ischemic preconditioning of muscle flap in a rat model. Ann Plast Surg 52 (2004) 609-613
69. Wang W.Z., Anderson G., Maldonado C., et al. Attenuation of vasospasm and capillary no-reflow by ischemic preconditioning in skeletal muscle. Microsurgery 17 (1996) 324-329
70. Cheng M.H., Chen H.C., Wei F.C., et al. Combined ischemic preconditioning and laser Doppler measurement for early division of pedicled groin flap. J Trauma 47 (1999) 89-95
71. Przyklenk K., Bauer B., Ovize M., et al. Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 87 (1993) 893-899
72. Küntscher M.V., Schirmbeck E.U., Menke H., et al. Ischemic preconditioning by brief extremity ischemia before flap ischemia in a rat model. Plast Reconstr Surg 109 (2002) 2398-2404
73. Küntscher M.V., Kastell T., Sauerbier M., et al. Acute remote ischemic preconditioning on a rat cremasteric muscle flap model. Microsurgery 22 (2002) 221-226
74. Addison P.D., Neligan P.C., Ashrafpour H., et al. Noninvasive remote ischemic preconditioning for global protection of skeletal muscle against infarction. Am J Physiol Heart Circ Physiol 285 (2003) H1435-H1443
75. Küntscher M.V., Juran S., Altmann J., et al. Role of nitric oxide in the mechanism of preclamping and remote ischemic preconditioning of adipocutaneous flaps in a rat model. J Reconstr Microsurg 19 (2003) 55-60
76. Takaoka A., Nakae I., Mitsunami K., et al. Renal ischemia/reperfusion remotely improves myocardial energy metabolism during myocardial ischemia via adenosine receptors in rabbits: effects of "remote preconditioning". J Am Coll Cardiol 33 (1999) 556-564
77. Dickson E.W., Lorbar M., Porcaro W.A., et al. Rabbit heart can be "preconditioned" via transfer of coronary effluent. Am J Physiol 277 (1999) H2451-H2457
78. Schoemaker R.G., and van Heijningen C.L. Bradykinin mediates cardiac preconditioning at a distance. Am J Physiol Heart Circ Physiol 278 (2000) H1571-H1576
79. Moses M.A., Addison P.D., Neligan P.C., et al. Mitochondrial KATP channels in hindlimb remote ischemic preconditioning of skeletal muscle against infarction. Am J Physiol Heart Circ Physiol 288 (2005) H559-H567
80. Wynn R.M., Davie J.R., Cox R.P., et al. Molecular chaperones: heat-shock proteins, foldases, and matchmakers. J Lab Clin Med 124 (1994) 31-36
81. Reed R.C., and Nicchitta C.V. Chaperone-mediated cross-priming: a hitchhiker's guide to vesicle transport (review). Int J Mol Med 6 (2000) 259-264
82. Maines M.D. Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. Faseb J 2 (1988) 2557-2568
83. Goda N., Suzuki K., Naito M., et al. Distribution of heme oxygenase isoforms in rat liver. Topographic basis for carbon monoxide-mediated microvascular relaxation. J Clin Invest 101 (1998) 604-612
84. Clark J.E., Foresti R., Sarathchandra P., et al. Heme oxygenase-1-derived bilirubin ameliorates postischemic myocardial dysfunction. Am J Physiol Heart Circ Physiol 278 (2000) H643-H651
85. Parfenova H., Carratu P., Tcheranova D., et al. Epileptic seizures cause extended postictal cerebral vascular dysfunction that is prevented by HO-1 overexpression. Am J Physiol Heart Circ Physiol 288 (2005) H2843-H2850
86. Yang Z.F., Tsui T.Y., Ho D.W., et al. Heme oxygenase-1 potentiates the survival of small-for-size liver graft. Liver Transpl 10 (2004) 784-793
87. Martins P.N., Reuzel-Selke A., Jurisch A., et al. Induction of carbon monoxide in the donor reduces graft immunogenicity and chronic graft deterioration. Transplant Proc 37 (2005) 379-381
88. Koenig W.J., Lohner R.A., Perdrizet G.A., et al. Improving acute skin-flap survival through stress conditioning using heat shock and recovery. Plast Reconstr Surg 90 (1992) 659-664
89. Ghavami A., Nutt M.P., and Hardy S.P. Heat shock protein and high-dose aspirin: effects on random skin flap survival in a rat model. Ann Plast Surg 48 (2002) 60-67
90. Wang B.H., Ye C., Stagg C.A., et al. Improved free musculocutaneous flap survival with induction of heat shock protein. Plast Reconstr Surg 101 (1998) 776-784
91. Harder Y., Contaldo C., Klenk J., et al. Improved skin flap survival after local heat preconditioning in pigs. J Surg Res 119 (2004) 100-105
92. Harder Y., Amon M., Schramm R., et al. Heat shock preconditioning reduces ischemic tissue necrosis by heat shock protein (HSP)-32-mediated improvement of the microcirculation rather than induction of ischemic tolerance. Ann Surg 242 (2005) 869-878 [discussion: 78-9]
93. Rücker M., Schäfer T., Roesken F., et al. Local heat-shock priming-induced improvement in microvascular perfusion in osteomyocutaneous flaps is mediated by heat-shock protein 32. Br J Surg 88 (2001) 450-457
94. Rücker M., Schäfer T., Roesken F., et al. Reduction of inflammatory response in composite flap transfer by local stress conditioning-induced heat-shock protein 32. Surgery 129 (2001) 292-301
95. Rücker M., Kadirogullari B., Vollmar B., et al. Improvement of nutritive perfusion after free tissue transfer by local heat shock-priming-induced preservation of capillary flowmotion. J Surg Res 123 (2005) 102-108
96. Donski P.K., Franklin J.D., Hurley J.V., et al. The effects of cooling on experimental free flap survival. Br J Plast Surg 33 (1980) 353-360
97. Bastiaanse J., Nanhekhan L.V., Slaaf D.W., et al. Preservation of rat cremaster muscle microcirculation after prolonged cold storage and transplantation. J Surg Res 131 (2006) 41-48
98. Shaw W.W., Ko C.Y., Ahn C.Y., et al. Safe ischemia time in free-flap surgery: a clinical study of contact-surface cooling. J Reconstr Microsurg 12 (1996) 421-424
99. Amon M., Menger M.D., and Vollmar B. Heme oxygenase and nitric oxide synthase mediate cooling-associated protection against TNF-alpha-induced microcirculatory dysfunction and apoptotic cell death. Faseb J 17 (2003) 175-185
100. Kubulus D., Amon M., Roesken F., et al. Experimental cooling-induced preconditioning attenuates skin flap failure. Br J Surg 92 (2005) 1432-1438
101. Barker J.H., Hammersen F., Galla T.J., et al. Direct monitoring of capillary perfusion following normovolemic hemodilution in an experimental skin-flap model. Plast Reconstr Surg 86 (1990) 946-954
102. Miyawaki T., Jackson I.T., Elmazar H., et al. The effect of low-molecular-weight heparin in the survival of a rabbit congested skin flap. Plast Reconstr Surg 109 (2002) 1994-1999
103. Finseth F., and Zimmermann J. Prevention of necrosis in island myocutaneous flaps in the pig by treatment with isoxsuprine. Plast Reconstr Surg 64 (1979) 536-539
104. Stein H.J., Fayman M.S., Oosthuizen M.M., et al. Verapamil improves survival of rat hyperemic island skin flaps. Surgery 106 (1989) 617-622 [discussion: 22-3]
105. Küntscher M.V., Juran S., Menke H., et al. The role of pre-ischaemic application of the nitric oxide donor spermine/nitric oxide complex in enhancing flap survival in a rat model. Br J Plast Surg 55 (2002) 430-433
106. Matsumura H., Yoshizawa N., Vedder N.B., et al. Preconditioning of the distal portion of a rat random-pattern skin flap. Br J Plast Surg 54 (2001) 58-61
107. Frick A., Baumeister R.G., Menger M.D., et al. Secondary ischaemia in experimental free flaps-treatment by long acting prostacyclin analogues. Br J Plast Surg 52 (1999) 392-398
108. Salerno G.M., McBride D.M., Bleicher J.N., et al. Ciprostene and indomethacin partially reverse the mechanisms of distal end necrosis in the rat random skin flap. Ann Plast Surg 28 (1992) 526-533 [discussion: 34]
109. Jansen G.B., Torkvist L., Lofgren O., et al. Effects of calcitonin gene-related peptide on tissue survival, blood flow and neutrophil recruitment in experimental skin flaps. Br J Plast Surg 52 (1999) 299-303
110. Armstrong Jr. M., Kunar D.R., and Cummings C.W. Effect of pentoxifylline [corrected] on myocutaneous flap viability in pigs. Otolaryngol Head Neck Surg 109 (1993) 668-675
111. Pokorny A.T., Bright D.A., and Cummings C.W. The effects of allopurinol and superoxide dismutase in a rat model of skin flap necrosis. Arch Otolaryngol Head Neck Surg 115 (1989) 207-212
112. Gribbe O., Lundeberg T., Samuelson U.E., et al. Dexamethasone increases survival and attenuates induction of inducible nitric oxide synthase in experimental skin flaps. Ann Plast Surg 42 (1999) 180-184
113. Edström L.E., Balkovich M., and Slotman G.J. Effect of ischemic skin flap elevation on tissue and plasma thromboxane A2 and prostacyclin production: modification by thromboxane synthetase inhibition. Ann Plast Surg 20 (1988) 106-111
114. Kirschner R.E., Fyfe B.S., Hoffman L.A., et al. Ischemia-reperfusion injury in myocutaneous flaps: role of leukocytes and leukotrienes. Plast Reconstr Surg 99 (1997) 1485-1493 [discussion: 94-5]
115. Cetinkale O., Bilgic L., Ayan F., et al. Neutrophil-mediated injury in ischemic skin flaps: amelioration of ischemic injury by cyclosporine in the rat. Ann Plast Surg 37 (1996) 66-74
116. Cetinkale O., Bilgic L., Bolayirli M., et al. Involvement of neutrophils in ischemia-reperfusion injury of inguinal island skin flaps in rats. Plast Reconstr Surg 102 (1998) 153-160
117. Yoshida T., Engelman R.M., Engelman D.T., et al. Preconditioning of swine heart with monophosphoryl lipid A improves myocardial preservation. Ann Thorac Surg 70 (2000) 895-900
118. Maldonado C., Stadelmann W.K., Ramirez S., et al. Preconditioning of latissimus dorsi muscle flaps with monophosphoryl lipid a. Plast Reconstr Surg 111 (2003) 267-274
119. Harder Y., Contaldo C., Klenk J., et al. Preconditioning with monophosphoryl lipid A improves survival of critically ischemic tissue. Anesth Analg 100 (2005) 1786-1792
120. Moon C., Krawczyk M., Ahn D., et al. Erythropoietin reduces myocardial infarction and left ventricular functional decline after coronary artery ligation in rats. Proc Natl Acad Sci U S A 100 (2003) 11612-11617
121. Jelkmann W. Molecular biology of erythropoietin. Intern Med 43 (2004) 649-659
122. Lappin T.R., Maxwell A.P., and Johnston P.G. EPO's alter ego: erythropoietin has multiple actions. Stem Cells 20 (2002) 485-492
123. Sharples E.J., Patel N., Brown P., et al. Erythropoietin protects the kidney against the injury and dysfunction caused by ischemia-reperfusion. J Am Soc Nephrol 15 (2004) 2115-2124
124. Villa P., Bigini P., Mennini T., et al. Erythropoietin selectively attenuates cytokine production and inflammation in cerebral ischemia by targeting neuronal apoptosis. J Exp Med 198 (2003) 971-975
125. Saray A., Ozakpinar R., Koc C., et al. Effect of chronic and short-term erythropoietin treatment on random flap survival in rats: an experimental study. Laryngoscope 113 (2003) 85-89
126. Harder Y., Amon M., Matzen A., et al. Recombinant Human Erythropoietin for treatment of critically perfused flaps - More than erythropoiesis?. Kongrbd Chir Forum 35 (2006) 391-393
127. Boerger A.L., Snitkovsky S., and Young J.A. Retroviral vectors preloaded with a viral receptor-ligand bridge protein are targeted to specific cell types. Proc Natl Acad Sci U S A 96 (1999) 9867-9872
128. Engelhardt J.F., Ye X., Doranz B., et al. Ablation of E2A in recombinant adenoviruses improves transgene persistence and decreases inflammatory response in mouse liver. Proc Natl Acad Sci U S A 91 (1994) 6196-6200
129. Höckel M., and Burke J.F. Angiotropin treatment prevents flap necrosis and enhances dermal regeneration in rabbits. Arch Surg 124 (1989) 693-698
130. Uhl E., Barker J.H., Bondar I., et al. Improvement of skin flap perfusion by subdermal injection of recombinant human basic fibroblast growth factor. Ann Plast Surg 32 (1994) 361-365 [discussion: 5-6]
131. Carroll C.M., Carroll S.M., Schuschke D.A., et al. Augmentation of skeletal muscle flap survival using platelet derived growth factor. Plast Reconstr Surg 102 (1998) 407-415
132. Machens H.G., Morgan J.R., Berthiaume F., et al. Functional angiogenesis induction in epigastric islet flap rat model after genetic modification of fibroblasts. Langenbecks Arch Chir Suppl Kongressbd 115 (1998) 681-687
133. Machens H.G., Morgan J.R., Berthiaume F., et al. Platelet-derived growth factor-AA-mediated functional angiogenesis in the rat epigastric island flap after genetic modification of fibroblasts is ischemia dependent. Surgery 131 (2002) 393-400
134. Kryger Z., Zhang F., Dogan T., et al. The effects of VEGF on survival of a random flap in the rat: examination of various routes of administration. Br J Plast Surg 53 (2000) 234-239
135. Banbury J., Siemionow M., Porvasnik S., et al. Improved perfusion after subcritical ischemia in muscle flaps treated with vascular endothelial growth factor. Plast Reconstr Surg 106 (2000) 1541-1546
136. Padubidri A., and Browne Jr. E. Effect of vascular endothelial growth factor (VEGF) on survival of random extension of axial pattern skin flaps in the rat. Ann Plast Surg 37 (1996) 604-611
137. Zhang F., Fischer K., Komorowska-Timek E., et al. Improvement of skin paddle survival by application of vascular endothelial growth factor in a rat TRAM flap model. Ann Plast Surg 46 (2001) 314-319
138. Gurunluoglu R., Ozer K., Skugor B., et al. Effect of transfection time on the survival of epigastric skin flaps pretreated with adenovirus encoding the VEGF gene. Ann Plast Surg 49 (2002) 161-169
139. Lubiatowski P., Goldman C.K., Gurunluoglu R., et al. Enhancement of epigastric skin flap survival by adenovirus-mediated VEGF gene therapy. Plast Reconstr Surg 109 (2002) 1986-1993
140. Machens H.G., Salehi J., Weich H., et al. Angiogenic effects of injected VEGF165 and sVEGFR-1 (sFLT-1) in a rat flap model. J Surg Res 111 (2003) 136-142
141. Seify H., Bilkay U., and Jones G. Improvement of TRAM flap viability using human VEGF-induced angiogenesis: a comparative study of delay techniques. Plast Reconstr Surg 112 (2003) 1032-1039