Ex Vivo Thrombolysis to Salvage Free Flaps Using Machine Perfusion: A Pilot Study in a Porcine Model

Abstract

Background Mechanical evacuation of capillary thrombi in free flaps is difficult, and often requires thrombolytic therapy. Utilizing machine perfusion systems, the possibility rises to salvage free flaps ex vivo by administering high doses of thrombolytic agents. The primary aim of this pilot study in a porcine model is to investigate the feasibility of ex vivo thrombolysis using an extracorporeal perfusion machine. Methods A model of stasis-induced thrombosis was used in 12 free rectus abdominis flaps harvested from six Dutch Landrace pigs. Compromised flaps were ex vivo perfused with University of Wisconsin preservation solution and treated according to the following study groups: (1) 1 mg of tissue plasminogen activator (t-PA) as additive, (2) 3 mg of t-PA as an additive, and (3) no thrombolytic additive. Microcirculation was assessed using near-infrared fluorescence angiography. Results Pedicled abdominal flaps were created and thrombus formation was successfully induced. Eleven abdominal flaps were perfused using the modified heart-lung machine setup. Near-infrared fluorescence angiography showed delayed or no filling was noted in the control group. In comparison, the flaps which were perfused with 1 mg t-PA or 3 mg t-PA as additive showed increased fluorescence intensity curves. Conclusion This pilot study in a porcine model presents a reliable and reproductive stasis-induced thrombosis model in free flaps. By adding t-PA to a custom-made extracorporeal perfusion system, the indocyanine green fluorescence intensity curves increased of all flaps that were perfused with different dosages of t-PA as additives, indicating restoration of capillary pressure and microcirculatory inflow.

Towards Optimizing Sub-Normothermic Machine Perfusion in Fasciocutaneous Flaps: A Large Animal Study

“…The first group received continuous perfusion (CP) with Steen+. The flow rate was manually adapted throughout the perfusion to keep the measured pressure between 30 and 55 mmHg based on our previous experience in other models [27,28]. A second group received intermittent perfusion (IP) with Steen.…”

“…However, their innovative approach will require important optimization to overcome the current limitations and lower the current complication rate of 67% observed in their series on partial flap loss [16,25,26]. On the other hand, Brouwers and Kruit have explored machine perfusion-based approaches in muscle flaps to study ex vivo thrombolysis in flap salvage [27], as well as for extended preservation as a relevant model for vascularized composite allotransplantation (VCA) [18,28]. Our team later explored subnormothermic machine perfusion techniques in rat limbs, providing a proof of concept of the use of machine perfusion in VCA, including bone components [29][30][31][32].…”