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Ex vivo lung perfusion (EVLP) is considered a useful platform to evaluate, preserve and recondition grafts prior to lung transplantation (LTx). Reducing physical stress due to standard volume-controlled ventilation (VCV), might further prolong EVLP in time and reduce ventilator induced lung injury (VILI). An innovative approach might be the use of flow-controlled ventilation (FCV), a ventilation mode which controls inspiratory and expiratory flow. These properties can reduce atelectrauma and volutrauma related to standard VCV. This is the first study to evaluate the use of FCV during EVLP in a porince model. Porcine lungs were mounted on EVLP after 2 hours of warm ischemia and divided into 2 groups (n=7/group). EVLP was maintained for 6 hours and physiological parameters were continuously recorded. In the first group, lungs on EVLP were ventilated standardly (VCV, 7 ml/kg). In the second group, lungs were ventilated using FCV (7ml/kg). After EVLP, W/D ratios were taken of the right lung and the left lung was frozen while inflated in liquid nitrogen vapors and CT scanned. Results are demonstrated in figure 1. Pulmonary vascular resistance (PVR) was comparable between VCV and FCV (p=0.52). FCV significantly increased oxygenation (P/F ratios) (p=0.01), and better maintained dynamic compliance (p=0.03). There was no difference in W/D ratios between the groups (p=0.16). CT density measurements were decreased by FCV (p=0.05). FCV is feasible to ventilate pulmonary grafts during EVLP and improves oxygenation. The lower decline in compliance and lower CT density measurements in FCV might indicate a better preservation of alveolar recruitment since extravascular water content (W/D ratio) was similar between both groups. In conclusion, FCV ventilation might reduce injury related to standard volume-controlled ventilation. Using FCV mode during EVLP might stabilize and prolong EVLP time in the future and open the perspective to further actively recondition grafts. [ABSTRACT FROM AUTHOR]

Ex-vivo lung perfusion (EVLP) is currently considered a valuable option to preserve, reassess or recondition pulmonary grafts prior to lung transplantation (LTx). Both standard and extended criteria donors lungs have been studied in clinical trials. Usually, a 20% deterioration of physiological parameters during EVLP is considered detrimental for the graft and a reason to decline it. In this study, we report the relation between EVLP parameters and primary graft dysfunction (PGD) in a clinical LTx program. In our center the TransMedics OCSTM Lung device is used. The indication for EVLP was combined organ transplantation, graft re-assessment or prolonged preservation based on an institutional algorithm and available resources. Standard clinical EVLP parameters (mean pulmonary artery pressure (PAP), vascular resistance (VR) and driving airway pressure(DAP)) were compared between the first and final assessment. The % difference (Δ) between these time points was calculated. Graft outcome was expressed as presence of any PGD grade 3 (PGD 3) within 72 hours. Statistical analysis was performed using student T-test comparing patients with PGD 3 vs. without. Combined organ (liver-LTx) and LTx cases were analyzed separately as well as together. Data are presented in figure 1. In total, 12 lungs were included. Overall, all grafts met acceptance criteria during EVLP and were transplanted. Despite this, 58% of the patients developed PGD 3. No statistically significant difference in EVLP parameters was observed between patients who developed and did not develop PGD 3. Overall, the clinical EVLP parameters were within the limits of acceptance and even improved over time. Despite this, we observed a high incidence of PGD 3. At this moment it is not clear how to assess EVLP lungs in clinical use and predict the outcome after LTx. The role of EVLP in post-reperfusion injury requires further research. [ABSTRACT FROM AUTHOR]

Early outcome after lung transplantation (LTx) is often characterized by the presence of primary graft dysfunction (PGD). The exact role of the right ventricle (RV) in development of PGD and perioperative outcome is unknown. Firstly, increased afterload due to PGD might compromise RV function. Secondly, increased contractility and cardiac output (CO) of RV might contribute to pulmonary edema accumulation after reperfusion. We developed a unique large animal model to study RV behavior in a setting of pulmonary ischemia-reperfusion injury (IRI). The left lung (LL) of a domestic pig in clamping group [CLA] was clamped (3h warm ischemia) and reperfused (3h) in situ (n=6). During the final hour of reperfusion, contralateral right lung (RL) was clamped to force RV CO to the injured LL. Control animals [CON] were fully instrumented (n=5) and followed for 6 hours. The RV function was monitored using a conductance catheter measuring pressure-volume (PV) loops. Lung injury was assessed by wet to dry (W/D) ratio and ex-vivo computed tomography (CT). Data was analyzed in time using 2-way ANOVA test or student T-test. Pulmonary vascular resistance (PVR) rose significantly at hour 6 in [CLA], reflecting an increase of afterload due to IRI and RL camping (fig. A). RV Contractility was stable in [CON]. In [CLA], it increased in 2 animals (fig. D) and 4 animals developed RV failure (fig. B). Lungs were injured as reflected by higher W/D ratio (p=0.0019) and parenchymal density on CT (p=0.0089) of [CLA] LL compared to [CON]. RV response to increased afterload resulting from IRI occurs in a dichotomized way: with increased contractility or with failure. This occurs when the contralateral lung is clamped and mimics a specific intra-operative situation of sequential single LTx. Our model should be considered as an innovative platform to study the possible benefit of ECLS devices on RV function and PGD development after LTx. [ABSTRACT FROM AUTHOR]