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Controlled Delivery of bFGF Remodeled Vascular Network in Muscle Flap and Increased Perfusion Capacity Via Minor Pedicle

Published:November 22, 2007DOI:https://doi.org/10.1016/j.jss.2007.10.009

      Background

      The vascular pedicles of superficial skeletal muscles are classified as the dominant pedicle and the minor pedicle. The dominant pedicle can reliably provide adequate circulation to the entire muscle, but the minor pedicle cannot. Therefore, it is impossible to elevate an entire muscle flap based solely on the minor pedicle. We evaluated whether the delivery of basic fibroblast growth factor (bFGF) would remodel the vascular network in the muscle flap and increase the perfusion capacity via the minor pedicle.

      Methods

      Using a controlled delivery system with acidic gelatin hydrogel microspheres, bFGF (50 μg, FGF group) or phosphate-buffered saline (PBS group) was delivered to the rabbit gracilis muscle, which contained a single dominant pedicle and a minor pedicle. Seven days later, the gracilis muscle was elevated as a muscle flap on the minor pedicle, and the flap was wrapped with a silicone sheet to avoid vessel in-growth from surrounding tissue. At 7 d after operation, flap viability, microangiograms, and regional blood flow were evaluated.

      Results

      Flap viability in the FGF group (73.6 ± 20.5%) was significantly higher than that in the PBS group (19.7 ± 23.5%). Postmortem angiograms of the flap showed obvious communications between the distal vascular networks of the minor and dominant pedicles. Angiographic score and regional blood flow of the flap were significantly higher in the FGF group than in the PBS group.

      Conclusions

      Controlled delivery of bFGF to rabbit gracilis muscle increased the perfusion capacity via the minor pedicle, and the minor pedicle became able to solely provide sufficient circulation to the entire muscle.

      Key Words

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      References

        • Mathes S.J.
        • Nahai F.
        Classification of the vascular anatomy of muscles: Experimental and clinical correlation.
        Plast Reconstr Surg. 1981; 67: 177
        • Mathes S.J.
        Muscle flaps and their blood supply.
        in: Sherrell J.A. Robert W.B. Charles H.M. Grabb and Smith's plastic surgery. Lippincott-Raven, Philadelphia, PA1997: 61
        • Khan A.
        • Ashrafpour H.
        • Huang N.
        • et al.
        Acute local subcutaneous VEGF165 injection for augmentation of skin flap viability: Efficacy and mechanism.
        Am J Physiol Regul Integr Comp Physiol. 2004; 287: R1219
        • Pang Y.
        • Lineaweaver W.C.
        • Lei M.P.
        • et al.
        Evaluation of the mechanism of vascular endothelial growth factor improvement of ischemic flap survival in rats.
        Plast Reconstr Surg. 2003; 112: 556
        • Zhang F.
        • Lei M.P.
        • Oswald T.M.
        • et al.
        The effect of vascular endothelial growth factor on the healing of ischaemic skin wounds.
        Br J Plast Surg. 2003; 56: 334
        • Lineaweaver W.C.
        • Lei M.P.
        • Mustain W.
        • et al.
        Vascular endothelium growth factor, surgical delay, and skin flap survival.
        Ann Surg. 2004; 239 (discussion 873.): 866
        • Hosaka A.
        • Koyama H.
        • Kushibiki T.
        • et al.
        Gelatin hydrogel microspheres enable pinpoint delivery of basic fibroblast growth factor for the development of functional collateral vessels.
        Circulation. 2004; 110: 3322
        • Rees M.J.
        • Taylor G.I.
        A simplified lead oxide cadaver injection technique.
        Plast Reconstr Surg. 1986; 77: 141
        • Tabata Y.
        • Hijikata S.
        • Muniruzzaman M.
        • et al.
        Neovascularization effect of biodegradable gelatin microspheres incorporating basic fibroblast growth factor.
        J Biomater Sci Polym Ed. 1999; 10: 79
        • Sakakibara Y.
        • Nishimura K.
        • Tambara K.
        • et al.
        Prevascularization with gelatin microspheres containing basic fibroblast growth factor enhances the benefits of cardiomyocyte transplantation.
        J Thorac Cardiovasc Surg. 2002; 124: 50
        • Mian S.W.
        • Romita M.C.
        • Tuchler R.E.
        • et al.
        An experimental model for soft-tissue coverage of the traumatized distal lower extremity: The distally-based gracilis flap.
        J Reconstr Microsurg. 1991; 7: 109
        • Fujihara Y.
        • Koyama H.
        • Nishiyama N.
        • et al.
        Gene transfer of bFGF to recipient bed improves survival of ischemic skin flap.
        Br J Plast Surg. 2005; 58: 511
        • Rashid M.A.
        • Akita S.
        • Razzaque M.S.
        • et al.
        Co-administration of basic fibroblast growth factor and sucrose octasulfate (sucralfate) facilitates the rat dorsal flap survival and viability.
        Plast Reconstr Surg. 1999; 103: 941
        • Takeshita S.
        • Zheng L.P.
        • Brogi E.
        • et al.
        Therapeutic angiogenesis.
        J Clin Invest. 1994; 93: 662
        • Ohara N.
        • Koyama H.
        • Miyata T.
        • et al.
        Adenovirus-mediated ex vivo gene transfer of basic fibroblast growth factor promotes collateral development in a rabbit model of hind limb ischemia.
        Gene Ther. 2001; 8: 837
        • Kowallik P.
        • Schulz R.
        • Guth B.D.
        • et al.
        Measurement of regional myocardial blood flow with multiple colored microspheres.
        Circulation. 1991; 83: 974
        • Tsurumi Y.
        • Takeshita S.
        • Chen D.
        • et al.
        Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments collateral development and tissue perfusion.
        Circulation. 1996; 94: 3281
        • Lubiatowski P.
        • Goldman C.K.
        • Gurunluoglu R.
        • et al.
        Enhancement of epigastric skin flap survival by adenovirus-mediated VEGF gene therapy.
        Plast Reconstr Surg. 2002; 109: 1986
        • Park S.
        • Tepper O.M.
        • Galiano R.D.
        • et al.
        Selective recruitment of endothelial progenitor cells to ischemic tissues with increased neovascularization.
        Plast Reconstr Surg. 2004; 113: 284
        • Yang L.W.
        • Zhang J.X.
        • Zeng L.
        • et al.
        Vascular endothelial growth factor gene therapy with intramuscular injections of plasmid DNA enhances the survival of random pattern flaps in a rat model.
        Br J Plast Surg. 2005; 58: 339
        • Yi C.
        • Xia W.
        • Zheng Y.
        • et al.
        Transplantation of endothelial progenitor cells transferred by vascular endothelial growth factor gene for vascular regeneration of ischemic flaps.
        J Surg Res. 2006; 135: 100
        • Taniyama Y.
        • Morishita R.
        • Aoki M.
        • et al.
        Therapeutic angiogenesis induced by human hepatocyte growth factor gene in rat and rabbit hindlimb ischemia models: Preclinical study for treatment of peripheral arterial disease.
        Gene Ther. 2001; 8: 181
        • Carmeliet P.
        Mechanisms of angiogenesis and arteriogenesis.
        Nat Med. 2000; 6: 389
        • Asahara T.
        • Murohara T.
        • Sullivan A.
        • et al.
        Isolation of putative progenitor endothelial cells for angiogenesis.
        Science. 1997; 275: 964
        • van Royen N.
        • Piek J.J.
        • Buschmann I.
        • et al.
        Stimulation of arteriogenesis; a new concept for the treatment of arterial occlusive disease.
        Cardiovasc Res. 2001; 49: 543
        • Hershey J.C.
        • Baskin E.P.
        • Glass J.D.
        • et al.
        Revascularization in the rabbit hindlimb: Dissociation between capillary sprouting and arteriogenesis.
        Cardiovasc Res. 2001; 49: 618
        • Kondoh K.
        • Koyama H.
        • Miyata T.
        • et al.
        Conduction performance of collateral vessels induced by vascular endothelial growth factor or basic fibroblast growth factor.
        Cardiovasc Res. 2004; 61: 132
        • Calderon W.
        • Chang N.
        • Mathes S.J.
        Comparison of the effect of bacterial inoculation in musculocutaneous and fasciocutaneous flaps.
        Plast Reconstr Surg. 1986; 77: 785
        • Mathes S.J.
        • Alpert B.S.
        • Chang N.
        Use of the muscle flap in chronic osteomyelitis: Experimental and clinical correlation.
        Plast Reconstr Surg. 1982; 69: 815