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Graft rinse prior reperfusion in liver transplantation (LT) is believed to reduce the incidence of postreperfusion syndrome and improve clinical outcome. A MEDLINE search was performed to obtain a comprehensive review of the published literature dealing with graft rinse in LT. Moreover, all thirty-four LT centers in the Eurotransplant (ET) region were invited to participate in an online survey to whether or not graft rinse is performed and whether further research in the field is needed. Seventeen reports have been found to investigate graft rinse protocols in 1894 LT recipients. Eighteen of the thirty centers that participated in the online survey performed graft rinse prior reperfusion in LT. The most commonly used rinse solution was albumin. Nineteen centers stated interest in participating in a multicenter RCT in the field. The published literature does not provide concluding appraisal of the benefit of graft rinse in LT. Graft rinse protocols are not standardized and are based on personal experience. Appropriately designed clinical trials addressing the topic are demanded. The online survey appears to be a helpful tool for the evaluation of clinical practice and future research topics in the transplant community.

Complement plays a decisive role in postischemic tissue injury, a process responsible for severe damage after organ ischemia. Several pathophysiologic mechanisms initiated upon reperfusion are mediated by complement inducing microcirculatory disturbances. Here, we demonstrate the effects of complement inhibition using C1-esterase inhibitor (C1-INH) on microcirculation after liver ischemia by in vivo microscopy (IVM). In rats, the left liver lobe was clamped for 70 min. C1-INH was given 1 min prior to reperfusion. Controls received Ringer's solution. IVM was performed 30-100 min after reperfusion. Non-perfused acini decreased and sinusoidal perfusion increased substantially after treatment. Leukocyte adherence to sinusoidal and venular endothelium was markedly reduced by C1-INH. Transaminases were significantly decreased by C1-INH. Our data obtained by IVM suggest that complement activation is an early key event of ischemia/reperfusion injury. These observations demonstrate for the first time that reperfusion related microcirculatory disorders can be minimized by C1-INH. This compound should be evaluated in clinical application.

Endothelin-1 (ET) is derived from its precursor big-ET, secreted by endothelial cells of multiple origin. The role of ET peptides in the physiological responses after orthotopic liver transplantation (OLT) was investigated. Venous big-ET plasma levels were analysed by RIA in 28 patients before and after OLT. Samples for analysis were taken intraoperatively from 12 patients from the caval, portal and hepatic veins and the radial artery at multiple time points. Highest caval levels were found during the an-hepatic period and 60 min after reperfusion, followed by a drop and subsequent increase postoperatively. Highest levels in the hepatic and portal veins were detected during explanation and reperfusion. A different pattern was found in the radial artery. Values during rejection and infection were elevated compared with preoperative and postoperative levels. The heterogeneity of the kinetics points to different sites of ET generation, including liver and splanchnic circulation. It suggests a predominant paracrine secretion mode of ET peptides with various stimuli involved. Big-ET levels could reflect endothelial cell damage, as big-ET is generated intracellularly and biological activity is rather weak.

Disturbance in hepatic microcirculation and leucocyte-endothelium interaction after warm ischaemia represents one of the leading mechanisms for postoperative organ dysfunction. Recent studies have shown that pretreatment with antithrombin III (AT III) and aprotinin reduces the leucocyte-endothelium interaction in ischaemic small intestine and during extracorporal circulation in cardiac surgery. Standardized warm hepatic ischaemia and intravital fluorescence videomicroscopy was performed in an experimental study with rats. Animals were pretreated with AT III or aprotinin. Analysis of intravital videomicroscopy showed that the hepatic microcirculation after warm hepatic ischaemia in rats was significantly enhanced by AT III and aprotinin, most likely by reducing the leucocyte-endothelium interaction. We concluded that drug application before the Pringle manoeuvre might reduce the reperfusion damage after liver resection.

One of the most common complications after liver transplantation is primary graft dysfunction which results from severe deterioration of the microcirculation. The data obtained from our experimental studies indicate that N-acetylcysteine (NAC) is able to reduce the severity of ischemia/reperfusion injury and improves postoperative graft function after liver transplantation in rats. The aim of this pilot study was to evaluate the efficacy of NAC as a hepatoprotective agent under clinical conditions. A group of 30 liver transplanted patients were treated with NAC, and 30 patients (control group) were treated with a 5 % solution of glucose only. In the NAC group we observed a distinct reduction in ischemia/reperfusion injury and improved liver function with less elevated peak transaminases, better macrocirculation, improved liver synthesis function and a lower incidence of primary nonfunction compared with the control group. We conclude that NAC is a very promising substance for reducing graft dysfunction in clinical liver transplantation.

The study was designed to assess the gastrointestinal ischaemia and the influence of the specific Kupffer cell toxin gadolinium chloride (GdCl3) on the hepatic and extrahepatic endotoxin [lipopolysaccharide (LPS)] clearance during experimental orthotopic liver transplantation (OLT) in pigs. In eight pig liver transplantations, the donors received 20 mg/kg of GdCl3 24 h before explantation, while controls (n = 8) received normal saline. Gastric and sigmoid intramucosal pH (pHi), LPS and endotoxin-neutralising capacity (ENC) levels were measured in the portal vein and superior vena cava after laparatomy, at the end of the anhepatic phase and 1 h after reperfusion. During the anhepatic phase, the sigmoid pHi decreased significantly from 7.32 ± 0.02 to 7.29 ± 0.03 (P < 0.001) and was associated with a substantial increase of portal LPS. Following reperfusion, the systemic LPS concentrations were significantly lower in the pretreated group [39 ± 23 pg/ml (Control); 14 ± 7 (GdCl3); P < 0.05] suggesting an improved liver LPS clearance [86 % (GdCl3); 58.2 % (Control); P < 0.05]. This corresponded to an increased ENC in the pretreated group [118 ± 52 ENU/ml (GdCl3) vs 81 ± 45 ENU/ml (Control); P < 0.05]. The anhepatic phase induced splanchnic ischaemia which correlated with portal endotoxaemia. Donor preconditioning with GdCl3 leads to lower systemic LPS concentrations in the recipient and increases ENC values in the early phase after OLT. An improved hepatocellular LPS extraction and/or an activation of the extrahepatic reticulo-endothelial system as a result of GdCl3 treatment is discussed.