Comparative study of lung preconditioning protocols in donors after circulatory arrest: an experimental rabbit model

Commentary: Who should be using ex vivo lung perfusion?

Inflammatory Response after Immediate versus Delayed Ex-Vivo Lung Perfusion in a Porcine Cardiac Arrest Donation Model

Metabolites in Human Ex Vivo Lung Perfusates Are Differentially Affected in Brain Death (BDD) vs. Cardiac Death Donors (DCD) and Modified by Duration of Normothermic Perfusion

91 Reconditioning of Lungs from Non-Heart-Beating Donors with Normothermic Ex Vivo Lung Perfusion

Gene Expression Change Related Inflammation Pathway during Rat EVLP and Heat Stress

Background Ex vivo lung perfusion (EVLP) has been developed to evaluate the quality of donor lungs before transplantation. EVLP may also serve as a platform, allowing administration of various therapies to the lungs. Aims We explored whether a mixed EVLP protocol combining normothermic and subnormothermic conditions would improve the quality of damaged rat donor lungs. Methods Rats were assigned into 2 groups (n=5 per group): Normothermic EVLP (Nth) and Normothermic/Subnormothermic EVLP, (N/Sth). In both groups lungs were kept in situ for 1h at room temperature, warm ischemia, then lungs were flashed with cold Perfadex® and kept for 1h at 4°C. Heart-lung blocks were mounted on the EVLP. In the Nth group lungs were perfused under normothermic conditions at 37°C for 6h. In the group N/Sth lungs were also perfused for 6h, first 3h under normothermia, then the perfusate temperature was reduced to 22° C, as well as ventilation and perfusion rates were also slow down to the end of EVLP. At the end of EVLP perfusates and lung tissues were collected and frozen at -80°C for further analysis. Results Lungs in the N/Sth group displayed improved compliance, and reduced edema, associated with reduced perfusate levels of lung endothelial and epithelial cell damage markers (vWF, SP-D, sPECAM-1), cytokines (IL-1β, and TNF-α) and lactate, comparing to Nth group. Moreover, increased production of cell protective proteins such as HSP70, antiapoptotic proteins (Bcl-2, Bcl-xL) and antioxidant (SOD2) was observed in N/Sth group. Conclusion Combination of normothermic and subnormothermic conditions during EVLP could be a promising experimental model providing improved cytoprotective status and preserved function of damaged donor lungs in an extended EVLP model. Our findings demonstrated that combination of normothermic and subnormothermic conditions during EVLP, allows safe extension of EVLP for possible treatments engaging prolonged perfusion time, while maintaining lungs in stable physiological state.

BackgroundUtilization rate of donor lungs in China is constrained by the inefficiency of conventional cold preservation (COLD) in lung transplantation. We assessed the performance of normothermic ex vivo lung perfusion (EVLP) in lung donors following cardiac death (DCD) with fresh EVLP perfusate.MethodsA total of 24 adult Sprague-Dawley (SD) rats were randomized into three groups (EVLP, COLD, and control groups) with 8 rats each. Fresh EVLP perfusate was prepared for lung perfusion. The pH, electrolyte concentration, perfusate penetration pressure during irrigation, physiological function, integrity of barrier function, pathological changes, and expressions of inflammation-related cytokines of donor lungs were examined.ResultsThe pH, electrolyte concentration, osmotic pressure of the perfusate were kept stable for 4 hours after EVLP was administered. Pulmonary arterial pressure (PAP), pulmonary venous pressure (PVP), pulmonary venous oxygenation index (PaO2/FiO2), and end carbon dioxide partial pressure (PCO2) in the EVLP group were all within acceptable limits. After 4 hours, the oxygenation index was significantly higher in the EVLP group compared with that of the COLD group (P=0.0032). The EVLP group had a decreased wet/dry weight ratio (P=0.0155) and Evans blue dye content (P=0.0075) compared to that of the COLD group. Pathological examination showed more obvious lung damage in the COLD group than in the EVLP group. However, there was no difference in protein expression of high mobility group box 1 (HMGB1) and toll-like receptor 4 (TLR4) between the EVLP group and the COLD group.ConclusionsFresh lung perfusate could be used for EVLP to protect and repair donor lungs. Normothermic EVLP performed better than conventional cold preservation. EVLP might be powerful for lung quality maintenance and may have potential for anti-inflammation.

Transient hyperthermia during ex vivo lung perfusion has no protective effect in rat model

Reconditioning of lungs donated after circulatory death with normothermic ex vivo lung perfusion

Ex vivo lung perfusion (EVLP) is a useful technique for evaluating and repairing donor lungs for transplantation. However, studies examining the effects of perfusate temperature on graft function are limited. Thus, this study aimed to examine these effects during EVLP on ischemic-reperfusion injury in the donor lung. Twenty-four male Sprague-Dawley rats were randomly divided into three groups, as follows: no treatment (sham group, n=5), normothermic EVLP (37 °C, n=5), and subnormothermic EVLP (30 °C, n=5). Lung function analyses, including oxygen capacity (OC), compliance, and pulmonary vascular resistance (PVR), were performed hourly during EVLP. Further, after 4 h of EVLP, histological evaluation of the right lobe was performed using the lung injury severity (LIS) scale. The expression levels of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-18 were evaluated. Metabolomic analysis of left lung tissues was conducted using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) after 4 h of EVLP in the EVLP groups and after 1 h of cold preservation in the sham group. Compared with those in the normothermic group, in the subnormothermic group, functional parameters during EVLP and subsequent histologic results were significantly superior, expression levels of inflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-18 were significantly lower, and glycolytic activity was significantly decreased. Furthermore, expression levels of mammalian target of rapamycin complex (mTORC), hypoxia-inducible factor (HIF) 1α, and nucleotide-binding domain, leucine-rich-containing family pyrin domain containing 3 (NLRP3) and its effector caspase-1 were significantly lower in the subnormothermic group than in the normothermic group. EVLP with subnormothermic perfusion improves lung graft function by reducing the expression of pro-inflammatory cytokines and glycolytic activity during EVLP. Additionally, EVLP can be a useful target for the improvement of graft function after transplantation.

Experimental Ex Vivo Lung Perfusion with Sevoflurane: Effect on donors after circulatory death (DCD) lung grafts in a rodent model.

Cytokine Expression Profile in Human Lungs Undergoing Normothermic Ex-Vivo Lung Perfusion

Successful Transplantation of Porcine Lungs Following 3 Days of Preservation Using a Modified Cold Static Method Paired with Intermittent Normothermic Ex Vivo Lung Perfusion (EVLP)

(113) - Optimal Oxygenation in Lung Graft Circulation during Ex Vivo Lung Perfusion

Reperfusion Inflammatory State of Human Lungs during Cellular Ex-Vivo Perfusion