Normothermic ex vivo lung perfusion of non-heart-beating donor lungs in pigs: from pretransplant function analysis towards a 6-h machine preservation

Abstract

Summary Donor shortage urges optimal use of all lungs available. Ex vivo lung perfusion (EVLP) is a method to evaluate lung function before implantation. EVLP was performed in pigs to evaluate lung function, using two different clinical non‐heart‐beating (NHS) donor protocols: flush perfusion and topical cooling after 1‐h warm ischaemia (n = 5 each). Secondly, we investigated whether EVLP can be used for 6 h ex vivo machine preservation (n = 4). In comparison with topical cooling, flush perfusion preserved lung function better during EVLP. During 6 h normothermic EVLP, gas exchange remained stable; however, the pulmonary artery pressure and ventilation pressure showed a significant increase. EVLP is a reliable method for evaluation of lung graft function. Flush perfusion with Perfadex is preferred above topical cooling in NHB lung donation. Six‐hour normothermic EVLP is feasible but should be further improved to make ex vivo machine preservation or treatment of lung grafts successful.

Extracorporeal perfusion of isolated organs of large animals – Bridging the gap between in vitro and in vivo studies

“…Attempts to establish a set-up for prolonged lung preservation showed promising results after six hours of perfusion, although impairment of lung function occurred towards the end of the experiment. The perfusate of choice was blood diluted with Steen ® solution (final haematocrit 15%), from which leukocytes and platelets had been eliminated (Erasmus et al, 2006). Stable lung function for up to twelve hours of perfusion with cell free Steen ® solution was reported later (Cypel et al, 2008).…”

“…As indicated above, this approach improves tissue oxygenation despite the reduced concentration of erythrocytes (Dittrich et al, 2000). Reported diluents have been cell free solutions (Domingo-Pech et al, 1991;Wagner et al, 2003;Erasmus et al, 2006;Friebe et al, 2013b) or autologous plasma (Patan et al, 2009;Patan-Zugaj et al, 2012, which comes with the added benefit of increasing oncotic pressure. As cell free solutions are associated with low oncotic pressure, resulting in edema formation and weight gain, adding plasma expanders such as plasma proteins (Verbeke et al, 1968;Roets et al, 1974;Patan et al, 2009) and purified albumin (Rehfeld et al, 1982;Barthel et al, 1989;Riviere et al, 1989;Brunicardi et al, 2001) perfused specimens thus reflects the degree of ischemia/reperfusion injury (Petrasek et al, 1994;Adham et al, 1997) and the integrity of the microvasculature (Müller et al, 2013).…”

“…Vasoconstriction, a core response in reperfusion injury, may be counteracted by the addition of vasodilators such as nitroglycerin (Domingo-Pech et al, 1991) or prostacyclin (Erasmus et al, 2006), which improve flow rates. Especially in udder perfusion studies, when aspects of milk production are at the center of interest and relatively high flow rates are required, blockage of 5-hydroxytryptamine induced vasoconstriction has been shown to be advantageous (Roets et al, 1974(Roets et al, , 1979a.…”

Ex-vivo Lung Perfusion and Its Role in Experimental Studies

“…To date, EVLP is a method used not only for evaluation of NHBD but also for the evaluation and treatment of marginal organs of braindead patients (14,15). Primary indications are slippery slopes such as decreasing PaO 2 /FiO 2 rates (300 mmHg), detecting pulmonary edema by physical examination and imaging, lower compliance parameter, high blood transfusion history, and longer duration of cardiac arrest (60 minutes) (16).…”

Pulsatile flow does not improve efficacy in ex vivo lung perfusion.

“…Table 4 displays all the clinical studies that investigate EVLP as a safe and efficient technique for lung preservation. Table IV: Recent clinical trial data for EVLP [64] L. Past, Present, and Future Directions in EVLP Studies have indicated cytokine accumulation as a potential mechanism for graft dysfunction [66,67]. Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are both associated with the inflammatory response and have been shown to increase after 6 hours of EVLP [68].…”