Abstract
Ischemia-reperfusion injury is a key mechanism of graft damage during lung transplantation, which could be targeted by therapies applied during ex-vivo lung perfusion (EVLP). The inhalational anaesthetic Sevoflurane was found to protect to some degree against ischemia-reperfusion injury1. In this experimental study we wanted to determine the therapeutic potential of volatile Sevoflurane added to the perfusate during EVLP of damaged lung grafts. Two groups of 6 Sprague-Dawley rats were used. After cardiac arrest and a warm ischemic time of 1 hour the lungs were flushed with cold Perfadex®, harvested and kept for 2 hours at 4°C. Normothermic EVLP during 3 hours was performed using a customized circuit primed either with Steen solution® only (control group) or supplemented within the first 30 minutes of EVLP with a gas mixture containing 2% of sevoflurane (treatment group). Differential oxygen partial pressures in the perfusate (ΔvapO2), pulmonary artery pressure (PAP), vascular resistance (PVR), lung compliance (LC), peak airway pressure (PAWP) and lung weight gain (WG) were measured. At the end of EVLP, protein and lactate dehydrogenase (LDH) levels were determined in bronchoalveolar lavage (BAL) and interleukin-6 (IL-6) and protein carbonyl (index of oxidative stress) were measured in lung tissue. Normothermic EVLP of lungs harvested after warm ischemia resulted in markedly declined ΔvapO2, LC, and elevated PAP, PVR, PAWP, WG. In contrast, lungs treated with Sevoflurane during EVLP displayed significantly improved LC, reduced weight gain and significantly lower LDH and protein carbonyl levels as compared to controls. PAWP and IL-6 were diminished in treated lungs, but were not statistically different to controls. The intravascular administration of sevoflurane during EVLP reduces oxidative stress and improves the functional status of DCD rat lungs in this experimental setting.
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