The Importance of Microcirculation and the Pathophysiological Role of Endothelin-1 in Liver Surgery and Transplantation

Abstract

The complex functions of the liver in metabolism, biosynthesis, and clearance, are all dependent on microcirculation. Despite growing data demonstrating the role of microcirculation in regulating liver function, this knowledge has not been translated into clinical practice. The aim of this study is to quantify hepatic microcirculation in-vivo using Side-stream dark field (SDF) imaging in order to predict the risk of early allograft dysfunction (EAD) or postoperative liver failure after liver resection and transplantation. Microcirculation parameters were correlated with hepatic blood flow, hemodynamic parameters, and soluble mediators. The study investigates also the role of endothelin-1 (ET-1), a modulator of the microcirculation, as marker of hepatic and renal functions. Materials and Methods Study 1 describes the use of SDF in 35 patients undergoing liver resection. Study 2 describes the use of SDF in 28 patients undergoing LT and the relationship between microcirculation with hemodynamics. Study 3 describes the impact of technique of reperfusion on microcirculation, and its correlation with gene expression, and serum markers. Seventy patients undergoing LT were randomized in two groups, sequential versus simultaneous reperfusion. Study 4 investigates the importance of ET-1 axis in predicting the risk of acute kidney injury in LT. Microcirculation measurement by SDF included functional sinusoidal density, sinusoidal diameter, red blood cell velocity, volumetric blood flow, and flow heterogeneity. The serum concentrations of ET-1, and 4 cytokines were analyzed with Luminex. Gene expression was assessed with qPCR. Results Study 1 demonstrates that low residual volume is associated with microcirculation dysfunction which is predictive of liver function. ET-1 and sRAGE level were also correlated to post-operative liver dysfunction. Study 2: SDF assessment post reperfusion was predictive of the risk of developing EAD. Study 3: demonstrates that ET-1 level is an independent predictor of EAD and AKI post-LT. Study 4: Despite longer warm ischemic time, simultaneous reperfusion caused less microcirculatory disturbance and superior primary function. Conclusions Assessment of the microcirculation in real time can be used to identify patients at risk of EAD or postoperative liver dysfunction who may benefit from surgical or pharmacological intervention. Despite longer warm ischemic time, simultaneous reperfusion causes less microcirculatory disturbance and improved functions in marginal grafts