Abstract
The process of brain death (BD) detrimentally affects donor lung quality. Ex vivo lung perfusion (EVLP) is a technique originally designed to evaluate marginal donor lungs. Nowadays, its potential as a treatment platform to repair damaged donor lungs is increasingly studied in experimental models. Rat models for EVLP have been described in literature before, yet the pathophysiology of BD was not included in these protocols and prolonged perfusion over 3 hours without anti-inflammatory additives was not achieved. We aimed to establish a model for prolonged EVLP of rat lungs from brain-dead donors, to provide a reliable platform for future experimental studies. Rat lungs were randomly assigned to one of four experimental groups (n = 7/group): 1) healthy, directly procured lungs, 2) lungs procured from rats subjected to 3 hours of BD and 1 hour cold storage (CS), 3) healthy, directly procured lungs subjected to 6 hours EVLP and 4), lungs procured from rats subjected to 3 hours of BD, 1 hour CS and 6 hours EVLP. Lungs from brain-dead rats showed deteriorated ventilation parameters and augmented lung damage when compared to healthy controls, in accordance with the pathophysiology of BD. Subsequent ex vivo perfusion for 6 hours was achieved, both for lungs of healthy donor rats as for pre-injured donor lungs from brain-dead rats. The worsened quality of lungs from brain-dead donors was evident during EVLP as well, as corroborated by deteriorated ventilation performance, increased lactate production and augmented inflammatory status during EVLP. In conclusion, we established a stable model for prolonged EVLP of pre-injured lungs from brain-dead donor rats. In this report we describe tips and pitfalls in the establishment of the rat EVLP model, to enhance reproducibility by other researchers.
Highlights
Brain-dead, multi-organ donors have the potential to save multiple lives of patients suffering from end-stage organ failure
Multiple rat ex vivo lung perfusion (EVLP) models have previously been described in literature, yet the brain death (BD)-induced pathophysiology and resulting lung damage was not included in these reports
Rat EVLP models currently described in literature, are commonly performed with lungs procured from living, anesthetized rats or from rats deceased after circulatory arrest, and require anti-inflammatory additives to enable perfusion for more than 3 hours (Table 3) [14]
Summary
Brain-dead, multi-organ donors have the potential to save multiple lives of patients suffering from end-stage organ failure. A translational rat model for ex vivo lung perfusion of pre-injured lungs after brain death deterioration of graft quality, to which donor lungs seem susceptible [1]. EVLP is suggested to be a promising platform to treat donor lungs in an isolated manner, in an attempt to repair damaged donor lungs and possibly improve lung graft survival after transplantation [5]. Multiple rat EVLP models have previously been described in literature, yet the BD-induced pathophysiology and resulting lung damage was not included in these reports. We aimed to develop a stable and reproducible rat EVLP model for prolonged perfusion of pre-injured donor lungs from brain-dead donors. This report details our successfully established protocol for BD and EVLP in rats, and describes tips and pitfalls to facilitate reproduction by other researchers
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