Retrograde thrombendarterectomy vs. ilio-femoral bypass in unilateral iliac TASC C and D lesions.

BACKGROUND: To compare short and long term results of retrograde Thrombendarterectomy (rTEA) and ilio-femoral Bypass (IFBP) to treat iliac TASC C and D lesions. PATIENTS AND METHODS: Retrospective analysis of 108 patients treated at a single vascular center by either rTEA (n = 42) or IFBP (n = 66) over a period of 4 years. RESULTS: Both methods did not significantly differ in 30-day (rTEA 0 % vs IFBP 2 %) or long-term mortality (rTEA 24 % vs IFBP 30 % at 4 years) with a median follow-up of 46 months. There were no procedure related deaths. Patency was similar for both groups (rTEA 93 % vs IFBP 98 % at 30 days; rTEA 83 % vs 92 % IFBP at 4 years). We could not find a significant difference in limb salvage rates (rTEA 93 % vs IFBP 100 % at 30 days and at 4 years). The incidence of prolonged lymphorrhea was significantly higher in the IFBP group (rTEA 0 % vs IFBP 21 %). In 4 IFBP patients a prosthetic graft infection occurred. CONCLUSIONS: Regarding short and long term results operative procedures as rTEA and IFBP still represent the gold standard in the treatment of TASC C and D lesions of the external iliac artery especially in patients with additional lesions in the common femoral and profundal femoral artery. Taking into account certain anatomical characteristics (heavily calcified lesions, narrow external iliac arteries or very tortuous iliac segments) and individual local conditions (prior vascular procedures involving the femoral bifurcation) the single incision retrograde approach to the EIA with rTEA may have advantages over IFBP, especially concerning postoperative complications like lymphorrhea and graft infection.

Use of biosynthetic prosthesis (Omniflow II®) to replace infected infrainguinal prosthetic grafts--first results.

BACKGROUND: The current treatment standard of infected infrainguinal prosthetic vascular grafts includes total graft explantation and autologous vascular reconstruction. In the absence of appropriate autologous venous graft material prosthetic grafts with increased bacterial resistance can be used, whereas reinfection rates are still higher than after autologous reconstruction. Biosynthetic grafts have shown low postoperative infection rates when used as elective bypass material. Their higher resistance to bacterial infection could make them an alternative to replace infected prosthetic grafts in the absence of autologous material. PATIENTS AND METHODS: Between November 2009 and April 2011, 7 patients with infected infrainguinal prosthetic grafts (Szilagyi 3; 3 supragenicular and 4 infragenicular reconstructions) presented to our institution. There were 4 early (< 3 months after implantation) and 3 late infections (> 3 months after implantation. All grafts were explanted and replaced by biosynthetic grafts (Omniflow II®), because the patient had no suitable peripheral vein for complete autologous replacement. In 2 cases a composite graft with greater saphenous vein was done. In 6 cases microbiological cultures from intraoperatively obtained species were positive. The initial broad spectrum antibiotic therapy was continued according to the antibiogram for 6 to 12 weeks. RESULTS: There was no early or late reinfection during follow up (mean 9 months, range 4 - 20 months). During follow up we observed graft occlusions in 3 patients (1 due to kinking of the bypass, 1 due to progressive artheriosclerotic occlusion of the outflow vessels and 1 iatrogenic by external compression with a pressure cuff during arthroscopy). There were no early or late major amputations. One patient died with pneumonia 11 months postoperatively. CONCLUSIONS: In the absence of appropriate autologous material biosynthetic grafts seem to be a possible alternative to replace infected infrainguinal grafts. The different mechanical properties of biosynthetic grafts may be of certain disadvantage in infragenicular reconstructions.

Dissecting the role of matrix metalloproteinases (MMP) and integrin alpha(v)beta3 in angiogenesis in vitro: absence of hemopexin C domain bioactivity, but membrane-Type 1-MMP and alpha(v)beta3 are critical.

Matrix metalloproteinase (MMP)-2 and its hemopexin C domain autolytic fragment (also called PEX) have been proposed to be crucial for angiogenesis. Here, we have investigated the dependency of in vitro angiogenesis on MMP-mediated extracellular proteolysis and integrin alpha(v)beta3-mediated cell adhesion in a three-dimensional collagen I model. The hydroxamate-based synthetic inhibitors BB94, CT1399, and CT1847 inhibited endothelial cell invasion, as did neutralizing anti-membrane-type 1-MMP (MT1-MMP) antibodies and tissue inhibitor of MMP (TIMP)-2 and TIMP-3 but not TIMP-1. This confirmed the pivotal importance of MT1-MMP over other MMPs in this model. Invasion was also inhibited by a nonpeptidic antagonist of integrin alpha(v)beta3, EMD 361276. Although PEX strongly inhibited pro-MMP-2 activation, when contaminating lipopolysaccharide was neutralized, PEX neither affected angiogenesis nor bound integrin alpha(v)beta(3). Moreover, no specific binding of pro-MMP-2 to integrin alpha(v)beta3 was found, whereas only one out of four independently prepared enzymatically active MMP-2 preparations could bind integrin alpha(v)beta3 , and this in a PEX-independent manner. Likewise, integrin alpha(v)beta3 -expressing cells did not bind MMP-2-coated surfaces. Hence, these findings show that endothelial cell invasion of collagen I gels is MT1-MMP and alpha(v)beta3 - dependent but MMP-2 independent and does not support a role for PEX in alpha(v)beta3 integrin binding or in modulating angiogenesis in this system.

Pharmacological inhibition of the vitronectin receptor abrogates PDGF-BB-induced hepatic stellate cell migration and activation in vitro.

BACKGROUND/AIMS: Activated hepatic stellate cells (HSC) play a central role in the development of liver fibrosis. Platelet-derived growth factor (PDGF)-BB and the integrin alphavbeta3 mediate mesenchymal cell migration and proliferation. However, their contribution and interaction during fibrogenic activation of HSC remains unclear. To this aim we investigated if PDFGF-BB and alphavbeta3 interact, and how far small molecular inhibitors of alphavbeta3 modulate PDGF-BB and serum-induced migration, proliferation and fibrogenic activation of HSC. METHODS: Rat and human HSC were subjected to migration and proliferation assays in the presence or absence of a peptide or a nonpeptide alphavbeta3 inhibitor. Activation of mitogen-activated protein kinases (ERK1/2, p38), Akt, focal adhesion kinase (FAK), paxillin and beta3 integrin was evaluated by phospho-specific Western blotting. Fibrosis related transcripts were determined by quantitative real-time PCR. RESULTS: PDGF-BB-stimulated HSC migration which was blocked dose-dependently by the alphavbeta3 antagonists, with complete inhibition at 10(-6)M. alphavbeta3 blockage did not affect cell viability or proliferation, while it decreased phosphorylation of FAK, paxillin, beta3 integrin and p38, but not of ERK1/2 or Akt. alphavbeta3 inhibition led to downregulation of certain profibrogenic transcripts, while it upregulated fibrolytic MMP-13 mRNA. CONCLUSIONS: Inhibition of integrin alphavbeta3 leads to abrogation of migration of HSC stimulated with PDGF-BB and to an antifibrogenic gene expression pattern.