Effects of cold or warm ischemia and ex-vivo lung perfusion on the release of damage associated molecular patterns and inflammatory cytokines in experimental lung transplantation

Abstract

Effects of cold or warm ischemia and ex-vivo lung perfusion on the release of damage associated molecular patterns and inflammatory cytokines in experimental lung transplantation,

Experimental Models of Ischemic Lung Damage for the Study of Therapeutic Reconditioning During Ex Vivo Lung Perfusion

“…Indeed, we previously reported that EVLP mitigated lung damage produced by WI alone, whereas it slightly enhanced the damage noted at the end of CI preservation. 9 In contrast, EVLP markedly amplified the release of inflammatory cytokines both in WI and CI lungs, consistent with the time required for de novo gene expression on reperfusion. 9 Time-course experiments would therefore be helpful to more precisely assess the evolution of lung injury after ischemia alone and after various durations of EVLP.…”

“… 9 In contrast, EVLP markedly amplified the release of inflammatory cytokines both in WI and CI lungs, consistent with the time required for de novo gene expression on reperfusion. 9 Time-course experiments would therefore be helpful to more precisely assess the evolution of lung injury after ischemia alone and after various durations of EVLP. Third, we did not evaluate injury patterns after extended durations of CI (>12 h) or prolonged WI times, as can be observed in uncontrolled DCD.…”

“…Interestingly, this was not paralleled by a larger release of BAL IL-6, implying no direct correlation between the degree of lung injury and inflammation during EVLP, in total agreement with our previous studies on innate immune mechanisms during EVLP and lung transplantation. 9 By reproducing many characteristics of PGD (oxidative stress, tissue injury, high permeability edema, reduced lung compliance, lung inflammation), these 2 models of W1h are well suited to study ex vivo therapeutic reconditioning, which aims at the repair of damaged lung grafts to reduce the risk of PGD after transplantation. The W50 model may be particularly relevant by amplifying the damage of WI through the simple increase of FiO 2 .…”

“…Interestingly, this was not paralleled by a larger release of BAL IL-6, implying no direct correlation between the degree of lung injury and inflammation during EVLP, in total agreement with our previous studies on innate immune mechanisms during EVLP and lung transplantation. 9 …”

“… 3 Using the W50 model, we recently reported significant benefits of ex vivo treatment with pharmacological inhibitors of poly(ADP-ribose) polymerase 10 , 11 and nuclear factor κ B, 8 and we also used this model to identify novel mechanisms of lung graft inflammation after EVLP and transplantation. 9 …”