Treatment with Bioartificial Liver Improves Lung Injury in a Swine Model of Partial Hepatectomy and Ischemia/Reperfusion

Abstract

Purpose Hepatic ischemia/reperfusion injury can lead to remote lung injury by inducing oxidative stress and inflammation. this study aims to investigate whether support of liver function with a bioartificial liver can attenuate remote lung injury after extended hepatectomy. Methods Fourteen domestic pigs were subjected to liver ischemia for 150 minutes and 70–75% hepatectomy. Six hours after initiation of hepatic reperfusion the animals were randomly allocated to a 6-hour treatment with a bioartificial liver (group B, n=7) or observation (group C, n=7). Hemodynamic and metabolic parameters were monitored for 24 hours following reperfusion. Lung biopsies were used for histological, nitrotyrosine and mrNA analysis. Results Oxygenation gradually deteriorated in group C, but was not significantly impaired in group B. Histological evaluation revealed improvements in alveolar collapse, necrotized pneumonocytes and lymphocyte infiltration in group B. Nitrotyrosine content of the lung was lower in group B compared to group C (55±12 vs. 132±22 nM/mg protein, p<0.01). Lung mRNA expression of interleukin-6, Stat-3 and E-selectin also decreased in group B. Expression of transforming growth factor-α mRNA did not differ between groups. Conclusions Application of a bioartificial liver was associated with improvement in several parameters of post-hepatectomy lung injury. the mechanisms appear to involve reduced nitrosative stress and attenuation of the native inflammatory process in the lung.