Document Detail

Activated protein C improves ischemic flap survival and modulates proangiogenic and antiinflammatory gene expression.
MedLine Citation:
PMID:  19182607     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Flap necrosis remains a major complication in reconstructive surgery. The authors evaluated whether systemic activated protein C, a natural serum anticoagulant with anti-inflammatory, proangiogenic, and cytoprotective properties, can improve ischemic skin flap survival.
METHODS: Cranially based dorsal cutaneous flaps were elevated on 44 rats. Animals received intravenous injections of activated protein C (25 microg/kg) or saline. Rats were divided into three groups depending on the timing of the first injection: postoperative (45 minutes postoperatively, n = 12), late preoperative (45 minutes preoperatively, n = 5), and early preoperative (3 hours preoperatively, n = 5). In all groups, second and third injections were performed at 3 and 24 hours postoperatively. Flap survival was measured on day 7. Histological and real-time polymerase chain reaction specimens were collected on days 2 and 7 and at 3 and 24 hours, respectively.
RESULTS: Postoperative activated protein C improved flap survival (68.9 +/- 4.3 percent) compared with control treatment (39.3 +/- 1.5 percent; p < 0.001). Late preoperative treatment produced diffuse flap hemorrhage. Early preoperative activated protein C injection produced near-complete flap survival (96.1 +/- 1.1 percent for activated protein C versus 50.1 +/- 3.3 percent for control; p < 0.001). Significantly fewer inflammatory cells, improved muscle viability, and increased blood vessel density were observed in activated protein C-treated versus control rats. Activated protein C treatment significantly reduced mRNA levels of intercellular adhesion molecule-1 and tumor necrosis factor-alpha, while increasing levels of Egr-1, vascular endothelial growth factor receptor 2, and Bcl-2.
CONCLUSIONS: Systemic activated protein C modulates genes involved in angiogenesis, inflammation and apoptosis and improves ischemic flap survival.
Michael Bezuhly; Steven F Morris; Ridas Juskevicius; R William Currie; Kenneth A West; Robert S Liwski
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Plastic and reconstructive surgery     Volume:  123     ISSN:  1529-4242     ISO Abbreviation:  Plast. Reconstr. Surg.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-02     Completed Date:  2009-03-02     Revised Date:  2014-10-13    
Medline Journal Info:
Nlm Unique ID:  1306050     Medline TA:  Plast Reconstr Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  502-15     Citation Subset:  AIM; IM    
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MeSH Terms
Apoptosis / drug effects,  physiology
Factor VIII / metabolism
Gene Expression Regulation / drug effects,  immunology
Intercellular Adhesion Molecule-1 / genetics
Interleukin-1beta / genetics
Ischemia / drug therapy*,  immunology*,  pathology
Neovascularization, Physiologic / drug effects*,  physiology
Protein C / pharmacology*
Rats, Sprague-Dawley
Recombinant Proteins / pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Surgical Flaps / blood supply,  pathology,  physiology*
Tumor Necrosis Factor-alpha / genetics
Reg. No./Substance:
0/Interleukin-1beta; 0/Protein C; 0/Recombinant Proteins; 0/Tumor Necrosis Factor-alpha; 126547-89-5/Intercellular Adhesion Molecule-1; 9001-27-8/Factor VIII

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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