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To investigate the impact of cerebral reperfusion on cardiac contractile function after normothermic regional perfusion (NRP) after anoxic circulatory death in a porcine model. The animals were anaesthetized and biventricular pressure-volume catheters and a pulmonary artery catheter were inserted percutaneously. Through a midline sternotomy, the heparinised animals were cannulated for extracorporeal circulation. Baseline data were obtained before cessation of mechanical ventilation. Death was determined 5 minutes after mechanical asystole and after additional 3 minutes of warm ischemia NRP was started using a heart-lung machine. The animals were randomized before reperfusion to either clamping (CL) (n=8) or non-clamping (NCL) (n=8) of the aortic arch vessels; the infrarenal aorta was clamped in both groups. The NRP-protocol includes early volume loading of the right ventricle, infusion of dobutamine and norepinephrine and gradual wean over 30 minutes. The animals were observed for 180 minutes after weaning from NRP. All animals were successfully weaned from NRP. Both groups demonstrated an acceptable cardiac function after weaning with a mean arterial blood pressure above 75 mmHg and low filling pressures. The NCL group received significantly more norepinephrine (p=0.0484) than the CL group. The left ventricle End-systolic pressure-volume relationship as an index of contractility showed improvement in both groups after wean from NRP compared to baseline (p=0.0009). In the CL group, LV contractility showed a tendency to a better improvement compared to the NCL group (p=0.226) (Fig. 1). The RV showed preserved contractility in both groups. LV contractility but not RV contractility improves after circulatory death and weaning from NRP. The improvement of the left ventricular contractility tends to be better when the aortic arch vessels are clamped compared to upper-body perfusion. [ABSTRACT FROM AUTHOR]

We present a research model that uses abattoir sheep lungs on ex vivo lung perfusion (EVLP). To best draw parallels, an EVLP animal model should be of comparable lung size, structure, circulatory and respiratory function. Especially, PaO 2 /FiO 2 , pulmonary artery- and left atrial pressures (PAP and LAP) and airway pressures should meet clinical standards. Contact was made with an abattoir willing to sell animal lungs for research. A faster procurement was negotiated, as well as on-site flushing and sampling. Six lungs from 20-30kg sheep were used. Pig lungs were unusable due to the boiling process they undergo. Sheep were stunned by a captive bolt pistol prior to exsanguination. Lungs were flushed and submerged in Perfadex Plus for 3 (n=4) or 7 hours (n=2) (hrs) of static cold storage (SCS). Each perfusion a home-made set was primed with 1.7L of buffered dextran-albumin solution (BDAs). Low flow (20% cardiac output) and tidal volume (6ml/kg BW) were chosen. Perfusion was run for 3 (n=4) or 7 (n=2) hrs. No extra perfusate was added in the 3hr runs. Lung biopsies, respiratory values, PAP and LAP were recorded and hourly blood gas analyses were performed. Mean oxygenation capacity remained stable with 47.1kPa pO 2 at 1hr and 47.2kPa pO 2 at 3hrs, p = 0.97. Our 7hrs perfusion case also remained stable between the 1st hr (47.8 kPa pO 2) and the 7th hr (pO 2 45.2 kPa). Furthermore pressures remained adequate both after 3hrs and 7hrs, a PAP ≤ 15 mmHg, LAP 3-5 mmHg and peak pressures ≤ 20 cmH 2 O. Mean wet weight/dry weight analyses showed an overall increase in oedema, 81.8% at procurement to 86.1% 3hrs post perfusion, p < 0.01. However, post-SCS (84.1%) versus 3hrs (86.1%) was not different, p = 0.14. When exchanging 1L of BDAs in the 7hrs experiment, fluid concentrations dropped from 85.9% at 2hrs post perfusion to 82.3% at 6hrs post perfusion. (Fig. 1) Abattoir animal lungs on EVLP are a good source for testing donor lung treatments. Three and 7hrs of SCS, as well as 3 and 7hr perfusions are possible. [ABSTRACT FROM AUTHOR]

Ex vivo lung perfusion (EVLP) is an established technique for the reconditioning and evaluation of marginal lungs. However, the use of EVLP for logistical reasons is still under discussion. We present our experience with EVLP for medical and logistical reasons. In this single center retrospective study, all EVLP's performed between July 2012 and October 2019 were analyzed. PaO 2, PVR, dynamic lung compliance and plateau airway pressure were analyzed for the EVLP's. PGD, lung function, CLAD free and overall survival were included for the lung transplant recipients. In total 50 EVLP's were performed, 33 for medical reasons which resulted in 26 lung transplants (MT) while 7 were rejected (MR). In addition, 17 EVLP's for logistical reasons resulted in 15 lung transplants (LT), 2 were rejected (LR). Pulmonary oedema was the main reason for rejection.During EVLP, there was an increase in PaO 2 in MT, PaO 2 remained stable in LT. Pre-EVLP PaO 2 was significantly lower in MT versus LT (p < 0.05) (Figure A). PVR increased in MR and LR (p = NS). At T180 PVR was significantly lower in LT compared to MT (Figure B). Dynamic lung compliance remained stable in LT and MT but decreased in MR and LR (p < 0.05 MT versus MR at T180 and T240) (Figure C). Plateau airway pressure was higher in MR and increased during EVLP in LR (p < 0.05 MT versus MR at T180) (Figure D). PGD scores were not significantly different between MT and LT at any time point. Lung function after 1 year was comparable between MT and LT (FEV 1 % 79.3% versus 68.7% ; p = NS (0.38), FVC% 82.2 versus 70.6; p = NS (0.27)). Five years CLAD free survival and overall survival were better after LT compared to MT (89% versus 62% and to 87% versus 66%; p = NS). Transplantation of lungs after logistic EVLP is safe and makes transplantation of lungs with otherwise very extended cold ischemia time more controllable.Furthermore, this study confirms that EVLP is an excellent tool for reconditioning of injured lungs and that lung compliance and plateau airway pressure are more important than PaO 2 in the evaluation on EVLP. [ABSTRACT FROM AUTHOR]

The impact of high versus low oxygenation during normothermic regional perfusion (NRP) after anoxic circulatory death on donor heart contractility in a porcine model. The animals were anaesthetized, pressure-volume catheters were placed in both ventricles and a pulmonary artery catheter was inserted percutaneously. Through a midline sternotomy, the heparinized animals were cannulated for extracorporeal circulation. Baseline data were obtained. Mechanical ventilation was withdrawn. After 15 minutes of warm ischemia, the aortic arch vessels and infrarenal aorta were clamped before NRP was commenced using a standard heart-lung machine. The animals were randomized to receive either FiO2 of 1.0 (HOX) or 0.21 (LOX) with a gradual increase to 0.40 during NRP. The NRP protocol includes early volume loading of the right ventricle and gradual wean over 35 minutes. Dobutamine and norepinephrine infusions were started during NRP for circulatory support. The animals were observed for 180 minutes after weaning from NRP. 15 of 19 animals were successfully weaned from NRP; 8/9 in the HOX and 7/10 in the LOX group, (p = 0.58). All weaned animals displayed acceptable cardiac function during the observation period and sustained a mean arterial pressure >60 mmHg with low filling pressures and cardiac index >2.5 L/min/m2. The preload independent end-systolic pressure volume relationship as an index of contractility was preserved in both groups. The HOX RV contractility was higher than the LOX group (p=0.035); and not significantly in the LV (p=0.37) (Fig. 1). Biochemestry showed lower lactate levels in the HOX group. There was no difference in norepinephrine requirement between groups. There were minimal haemodynamic and biochemical differences between the groups as all weaned animals demonstrated acceptable cardiac function. The high oxygenation group showed marginally better cardiac performance and lower lactate concentrations. [ABSTRACT FROM AUTHOR]

Ex Vivo Lung Perfusion (EVLP) is an excellent method to preserve and recondition donor lungs, thus increasing the lung donor pool. This systematic review summarizes studies comparing both primary graft dysfunction (PGD) and survival between EVLP and conventional lung transplantation (c-LTx), or between different EVLP protocols. The objective is to evaluate outcomes of the three main EVLP protocols: 'Lund', 'Toronto' and 'Organ Care System' (OCS), through a network meta-analysis (NMA). A systematic search was performed in Pubmed, Embase, the Cochrane library and Web of Science. Studies performing EVLP on initially discarded donor lungs were independently assessed for eligibility by two researchers. Data on study design, participants, and EVLP methods were extracted, together with outcomes such as survival and PGD. The generated database was assessed on meeting the assumptions for NMA. Nine studies were included: two non-randomised clinical trials (n = 240), and four prospective (n = 1360) and three retrospective observational cohort studies (n = 540). The study protocols could be divided into: Toronto (5/9), Lund (3/9) and OCS (1/9). Most frequently reported outcomes were PGD grade 3 at 72 hours post-LTx, and one-month and one-year survival. All included studies compared EVLP to c-LTx, providing solely indirect evidence for comparison between protocols and thus no loops within the NMA model. In the absence of loops, consistency within the model cannot be statistically assessed. Thus, thorough examination for differences that could modify the treatment effect is required. Substantial variations were found in study design, type of LTx, and participant characteristics. It was therefore not feasible to construct a subset of studies that met the similarity and consistency assumptions of NMA. Currently, no substantiated statistical comparison can be made between different EVLP protocols. Further attempts at NMA are dependent on the introduction of studies comparing multiple EVLP protocols, or an increase in randomised controlled trials performing EVLP on standard donor lungs. Alternatively, collaborative data management between EVLP centres would be a promising way to explore the effect of different protocols, and their individual components, on patient outcomes. [ABSTRACT FROM AUTHOR]