Different inflammatory cytokines release after open and endovascular reconstructions influences wound healing
Authors: Sapienza Paolo , Mingoli Andrea , Borrelli Valeria , Grande Raffaele , Sterpetti Antonio V. , Biacchi Daniele , Ferrer Ciro , Rubino Paolo , Serra Raffaele , Tartaglia Elvira 
Published: June 2019

Prodromal signs of a non‐healing wound after revascularisation, which might be strictly linked with impending failure of vascular reconstructions, are associated with an inflammatory response mediated by several circulating adhesion molecules, extracellular endopeptidases, and cytokines. The aim of our study was to investigate the role of selected plasma biomarkers in the prediction of both wound healing and failure of infrapopliteal vein graft or percutaneous trans‐luminal angioplasty (PTA) with selective stent positioning of the superficial femoral artery (SFA) in a population affected with critical limb ischaemia. A total of 68 patients who underwent either surgical or endovascular revascularisation of the inferior limb with autologous saphenous vein infrapopliteal bypass or PTA and selective stenting of the SFA were enrolled in our study. Patients were divided into two groups according to treatment: 41 patients were included in Group 1 (open surgery) and 27 in Group 2 (endovascular procedure). Plasma and blood samples were collected on the morning of surgery and every 6 months thereafter for up to 2 years of follow‐up or until an occlusion occurred of either the vein bypass graft or the vessel treated endovascularly. Fifteen age‐matched healthy male volunteers were considered a reference for biological parameters. Vascular cell adhesion molecule 1 [VCAM‐1]/CD106, inter‐cellular adhesion molecule‐1 [ICAM‐1]/CD54), interleukin‐1 (IL‐1), interleukin‐6 (IL‐6), tumour necrosis factor alpha (TNF‐α), and metalloproteinases (MMP)‐2 and ‐9 plasma levels were measured with enzyme‐linked immunosorbent assay (ELISA) kits. The mean observed time to heal of 54 wounds was 13 ± 4 months, with no statistically significant differences among the groups. The healing failure of the remaining wounds was strictly related to an unsuccessful open (n = 12) or endovascular (n = 8) treatment. The 2‐year primary patency rate was 65% (SE = .09) in Group 1 and 52% (SE = .1) in Group 2. When compared with mean concentration values of Group 1, VCAM‐1 and ICAM‐1 were always significantly higher during follow‐up in patients of Group 2 (P < .05). Furthermore, in the same group, IL‐6 and tumour necrosis factor alpha (TNF‐α) were found to be significantly higher at 6‐ and 12‐month (P < .05) when compared with surgically treated patients. Cox regression analysis showed that elevated plasma levels of VCAM‐1, ICAM‐1, IL‐6, and TNF‐α during follow up were strongly related to impaired wound healing and/or revascularisation failure (P < .05). Elevated plasma levels of inflammatory markers VCAM‐1, ICAM‐1, IL‐6, and TNF‐α may be related to the failure of wound healing and revascularisation procedures. Interestingly, we have observed that endovascular treatments cause a higher level of these inflammation biomarkers when compared with a vein graft, although wound‐healing and patency and limb salvage rates are not influenced.