Novel Biomarkers of Arterial and Venous Ischemia in Microvascular Flaps

Abstract

The field of reconstructive microsurgery is experiencing tremendous growth, as evidenced by recent advances in face and hand transplantation, lower limb salvage after trauma, and breast reconstruction. Common to all of these procedures is the creation of a nutrient vascular supply by microsurgical anastomosis between a single artery and vein. Complications related to occluded arterial inflow and obstructed venous outflow are not uncommon, and can result in irreversible tissue injury, necrosis, and flap loss. At times, these complications are challenging to clinically determine. Since early intervention with return to the operating room to re-establish arterial inflow or venous outflow is key to flap salvage, the accurate diagnosis of early stage complications is essential. To date, there are no biochemical markers or serum assays that can predict these complications. In this study, we utilized a rat model of flap ischemia in order to identify the transcriptional signatures of venous congestion and arterial ischemia. We found that the critical ischemia time for the superficial inferior epigastric fasciocutaneus flap was four hours and therefore performed detailed analyses at this time point. Histolgical analysis confirmed significant differences between arterial and venous ischemia. The transcriptome of ischemic, congested, and control flap tissues was deciphered by performing Affymetrix microarray analysis and verified by qRT-PCR. Principal component analysis revealed that arterial ischemia and venous congestion were characterized by distinct transcriptomes. Arterial ischemia and venous congestion was characterized by 408 and 1536>2-fold differentially expressed genes, respectively. qRT-PCR was used to identify five candidate genes Prol1, Muc1, Fcnb, Il1b, and Vcsa1 to serve as biomarkers for flap failure in both arterial ischemia and venous congestion. Our data suggests that Prol1 and Vcsa1 may be specific indicators of venous congestion and allow clinicians to both diagnose and successfully treat microvascular complications before irreversible tissue damage and flap loss occurs.

Transdermal application of azithromycin-amlodipine-heparin gel enhances survival of infected random ischaemic flap

“…Transdermal administration of these compound gels to in vivo random ischaemic flaps successfully attained therapeutic concentrations 2 hours after application. This result suggests that AZM, AB, and LMWH are able to get into flap tissue by transdermal application before either infection or irreversible injury caused by blood obstacles can occur [26,27].…”

Novel developments in non-invasive imaging of peripheral arterial disease with CT: experience with state-of-the-art, ultra-high-resolution CT and subtraction imaging

“…The evaluation of tissue perfusion and distinction between hyperaemia and congestion in damaged areas could also become important markers for avoiding major tissue loss. 24 Such information could also influence the decision to use invasive revascularisation or tissue reconstruction. The evaluation of tissue perfusion and its combination with microvascular imaging using UHRCT could provide useful information, especially for reconstruction surgery in critical limb ischaemia; however, such applications remain speculative at present, as currently there is only limited experience.…”

The Effect of Platelete Rich Plasma Combined with Microneedling on Full Venous Outflow Compromise in a Rat Skin Flap Model

“…2 Microneedling aims to induce as many microwounds in the dermis by the needle pricks as possible rolling needles vertically, horizontally and diagonally with pressure over the treated area. 3 Microneedling initiate the normal phases of wound healing.…”

“…1 We recently reported that affected subcutaneous adipose tissue in patients with FIL contains mutant cells with somatic gain-offunction mutations in PIK3CA. 2 The purpose of this study was to determine whether other affected tissues in FIL also contain mutant cells.…”