title: Targeted protection of donor graft vasculature using a phosphodiesterase inhibitor increases survival and predictability of autologous fat grafts.
abstract: BACKGROUND
  Fat grafting is limited by unpredictable long-term graft retention. The authors postulate that injury to the donor-derived microvasculature during harvest and subsequent ischemia may account for this clinical variability. They examined the use of the U.S. Food and Drug Administration-approved phosphodiesterase-5 inhibitor sildenafil citrate to protect graft microvasculature and its role in revascularization and survival.
  
  
  METHODS
  Inguinal fat of donor Tie2/LacZ mice was infiltrated with sildenafil or saline, harvested, and transplanted onto the dorsa of recipient FVB mice. Additional donor mice were perfused with intraarterial trypsin to inactivate the fat graft microvasculature before harvest and transplantation. Differences in graft revascularization, perfusion, volume of retention, and biochemical changes were assessed.
  
  
  RESULTS
  Surviving fat grafts were characterized by exclusively donor-derived vasculature inosculating with the recipient circulation at the graft periphery. Inactivation of donor-derived microvasculature decreased early graft perfusion and led to nearly total graft loss by 8 weeks. Sildenafil attenuated vascular ischemic injury, consistent with reductions in VCAM-1 and SDF1α expression at 48 hours and 4-fold increases in microvasculature survival by 2 weeks over controls. Compared with controls, targeted sildenafil treatment improved early graft perfusion, doubled graft retention at 12 weeks (83 percent versus 39 percent; p < 0.05), ultimately retaining 64 percent of the original graft volume by 24 weeks (compared to 4 percent; p < 0.05) with superior histologic features.
  
  
  CONCLUSIONS
  Fat graft vascularization is critically dependent on maintenance of the donor microvasculature. Sildenafil protects the donor microvasculature during transfer and revascularization, increasing long-term volume retention. These data demonstrate a rapidly translatable method of increasing predictability and durability of fat grafting in clinical practice.
authors: New York, N.Y. From the New York University Department of Plastic Surgery Laboratories, New York University Langone Medical Center.
authors: Marc A
authors: MA
authors: Soares
authors: Obinna C
authors: OC
authors: Ezeamuzie
authors: Maria J
authors: MJ
authors: Ham
authors: April M
authors: AM
authors: Duckworth
authors: Piul S
authors: PS
authors: Rabbani
authors: Pierre B
authors: PB
authors: Saadeh
authors: Daniel J
authors: DJ
authors: Ceradini
mesh_terms: D000273:Adipose Tissue / Q000098:blood supply / Q000637:transplantation*; D042683:Angiopoietin-1 / Q000378:metabolism; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism / Q000637:transplantation; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006085:Graft Survival; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D055806:Microvessels / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D011687:Purines / Q000008:administration & dosage / Q000627:therapeutic use; D042787:Receptor, TIE-2 / Q000235:genetics; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D020858:Tissue and Organ Harvesting / Q000379:methods; D014182:Transplantation, Autologous / Q000379:methods; D019737:Transplants / Q000098:blood supply*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D042683:Angiopoietin-1; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011687:Purines; D013449:Sulfonamides; D000068677:Sildenafil Citrate; D042787:Receptor, TIE-2; C079086:Tek protein, mouse
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