Postreperfusion microcirculatory derangements after liver transplantation: Relationship to hemodynamics, serum mediators, and outcome

Abstract

Despite the growing data supporting the role of microcirculation in regulating liver function, little of this knowledge has been translated into clinical practice. The aim of this study is to quantify hepatic microcirculation in vivo using sidestream dark field (SDF) imaging and correlate these findings with hepatic blood flow, hemodynamic parameters, and soluble mediators. Postreperfusion hepatic microcirculation was assessed using SDF imaging. Hepatic microcirculation measurements included functional sinusoidal density (cm/cm ), sinusoidal diameter (μm), red blood cell velocity (μm/second), volumetric blood flow (pl/second), and flow heterogeneity (FH) index. The serum concentrations of endothelin 1 (ET-1) and other inflammatory markers were analyzed with Luminex technology. Portal venous and hepatic artery flows were measured using a flowmeter. Twenty-eight patients undergoing cadaveric liver transplantations have been included in this study. Early allograft dysfunction (EAD) occurred in 7 (25%) patients and was associated with microcirculatory dysfunction. Low arterial and portal flow, high dose of inotropes, cold ischemia time, steatosis, and high ET-1 levels were all associated with impaired microcirculation. The time interval between portal venous and hepatic arterial reperfusion significantly correlated with the changes of the liver grafts' microcirculation. EAD patients tended to have higher serum levels of ET-1 on postoperative days 1, 2, 5, and 7 (all P < 0.01). Serum levels of ET-1 correlated significantly with microcirculation parameters. In conclusion, postreperfusion hepatic microcirculation is a determinant of organ dysfunction after liver reperfusion and could be used to identify very early patients at risk of EAD. Liver Transplantation 23 527-536 2017 AASLD.

Molecular profiling of postreperfusion milieu determines acute kidney injury after liver transplantation: A prospective study

“…Logistic regression analysis shows that ET‐1 and IL18 levels were independently associated with AKI. We have previously demonstrated that ET‐1 serum levels correlate with hepatic microcirculation dysfunction after reperfusion in LT . In addition to its role in IRI of the liver, ET‐1 is also an important mediator of renal physiology .…”

“…(13) Logistic regression analysis shows that ET-1 and IL18 levels were independently associated with AKI. We have previously demonstrated that ET-1 serum levels correlate with hepatic microcirculation dysfunction after reperfusion in LT. (14) In addition to its role in IRI of the liver, ET-1 is also an important mediator of renal physiology. (15) Experimental studies have shown that ET-1 causes marked and prolonged renal vasoconstriction, manifested by profound reduction in renal blood flow and glomerular filtration rate.…”

“…(15,16) Furthermore, the kidney appears to be more sensitive to exogenous ET-1 compared with all other organs. (17) In humans, there is growing evidence that the ET-1 system is activated early following acute injury, (18) including LT. (14) Early studies have suggested the potential association between AKI and ET-1 after LT but were limited by small samples sizes. (19)(20)(21) Also, different definitions of AKI have been used.…”

Platelets and Platelet‐Derived Extracellular Vesicles in Liver Physiology and Disease

“…Free reactive oxygen species are responsible for tissue injury but also for the amplification of this phenomenon. Further, liver ischemia‐reperfusion injury is characterized by alteration of the microcirculation . Platelets were shown to play a key role in this process.…”

“…Further, liver ischemia-reperfusion injury is characterized by alteration of the microcirculation. (106,107) Platelets were shown to play a key role in this process. First, platelets aggregate within sinusoids during the ischemic phase, contributing to the propagation of no-reflow zones during reperfusion.…”