Improving Ex-vivo Lung Preservation: How does viscosity of the perfusing liquid affect preservation of the ex-vivo lung (360G-Wellcome-207371_Z_17_Z)

Organ transplantation, including lung transplantation, is now a standard procedure used to treat irreversible organ failure. An important factor limiting this treatment option is a shortage of suitable donor organs. Frequently lungs that are considered "marginal" have to be discarded although they might be suitable for transplantation. Recently, it has been shown that ex vivo lung perfusion (EVLP) can "recondition" lungs before implantation, and permits the assessment and use of many organs that would otherwise be discarded. In the course of our research using isolated, ventilated, murine lungs, we have developed a novel modification of perfusion solutions that can preserve the normal function of these lungs for much longer periods than previously possible with conventional solutions. This was achieved by using high molecular weight polymers to increase the viscosity of the perfusate so that it mimicked that of blood within the microcirculation of the normal lung. We have already excluded shear-mediated mechanism for this beneficial effect and any action mediated by changes in osmolality. The proposed project will examine the effect of this novel perfusate on the heterogeneity of perfusion distribution throughout the mouse lung compared to that observed when using conventional perfusate solution.