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Background: Portal pressure (PP) results from the interplay of vasoconstrictors and vasodilators. Recently, we have shown that Kupffer cell (KC) activation increases PP., Aims: The role of the vasodilating compounds nitric oxide (NO) and carbon monoxide (CO) was studied. The hypothesis of the present study was that these vasodilators counteract the PP increase following KC activation., Methods: Livers of rats weighing 180-200 g were isolated and perfused. KCs were activated by zymosan A (cell wall particles from yeast; 150 µg/ml). The effects of NO and guanylate cyclase (GC) were evaluated by the NO synthase inhibitor N(G)-nitro-L-arginine methylester (L-NAME; 0.3 mM, and the GC inhibitor 4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one (NS-2028, 1.0 µM); the effects of the heme oxygenase (HO) derived compound CO were evaluated by direct administration of CO or inhibition of HO by zinc protoporphyrin IX (ZnPP IX, 1.0 µM)., Results: In isolated perfused rat livers, administration of L-NAME or NS-2028 further raised PP increase following KC activation. This effect could be reduced by the cGMP analogue 8-Br-cGMP. Inhibition of HO caused marked amplification of PP increase in zymosan-treated organs. CO prevented this PP increase cGMP independently. Interestingly, KC activation and simultaneous inhibition of HO augmented the production of prostaglandins D2 and F2α and of thromboxane A2. Accordingly, indomethacin blunted the increase of PP in zymosan/ZnPP-treated livers., Conclusions: NO restricts the initial PP increase after KC activation by GC-mediated cGMP. CO from heme degradation limits the increase of PP after KC activation eicosanoid dependently, but cGMP independently., (Copyright © 2013 S. Karger AG, Basel.)

Ischemia-reperfusion injury (IRI) is increased after transplantation of steatotic livers. Since those livers are increasingly used for transplantation, protective strategies must be developed. Reactive oxygen species (ROS) play a key role in hepatic IRI. In lean organs, glutathione (GSH) is an efficient scavenger of ROS, diminishing IRI. The aim of this study was to evaluate whether GSH also protects steatotic allografts from IRI following transplantation. Fatty or lean livers were explanted from 10-week-old obese or lean Zucker rats and preserved (obese 4 h, lean 24 h) in hypothermic University of Wisconsin solution. Arterialized liver transplantation was then performed in lean syngeneic Zucker rats. Recipients of fatty livers were treated with GSH (200 μmol/h/kg) or saline during reperfusion (2 h, n = 5). Parameters of hepatocellular damage and bile flow were measured. Transplantation of steatotic livers enhanced early reperfusion injury compared to lean organs as measured by increased aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase plasma levels. Bile flow was also reduced in steatotic grafts. Intravenous administration of GSH effectively decreased liver damage in fatty allografts and resulted in improved bile flow. Intravenous application of GSH effectively reduces early IRI in steatotic allografts and improves recovery of these marginal donor organs following transplantation., (Copyright © 2010 S. Karger AG, Basel.)

Background: The study aimed to explore the prevalence of psychiatric disorders among orthotopic liver transplantation (OLT) recipients, and to investigate how psychiatric morbidity was linked to health-related quality of life (HRQOL)., Methods: We recruited 75 patients who had undergone OLT a median of 3.8 years previously (range = 5-129 months). Psychiatric morbidity was assessed using the Structural Clinical Interview for the DSM-III-R. Psychometric observer-rating and self-rating scales were administered to evaluate cognitive functioning (SKT), depressive symptomatology (HAMD(17)), posttraumatic stress symptoms (PTSS-10), social support (SSS), and HRQOL (SF-36 Health Status Questionnaire). Treatment characteristics were obtained from medical records., Results: 22.7% (n = 17) of our sample had a current or probable psychiatric diagnosis according to DSM-III-R: 2.7% full posttraumatic stress disorder (PTSD) (n = 2), 2.7% major depressive disorder (MDD) comorbid to full PTSD (n = 2), 1.3% MDD comorbid to partial PTSD (n = 1), and 16% partial PTSD (n = 12). Patients with PTSD symptoms demonstrated lower cognitive performance, higher severity of depressive symptoms and more unfavorable perception of social support. OLT-related PTSD symptomatology was associated with maximal decrements in HRQOL. The duration of intensive care treatment, the number of medical complications, and the occurrence of acute rejection were positively correlated with the risk of PTSD symptoms subsequent to OLT., Conclusion: OLT-related PTSD symptomatology impairing HRQOL is a complication for a subgroup of OLT recipients. Health-care providers should be aware of the possible presence of PTSD in OLT survivors., (Copyright 2002 S. Karger AG, Basel)

Background/aim: The generation of reactive oxygen species by activated Kupffer cells (KC) may contribute to reperfusion injury of the liver during liver transplantation or resection. The aim of our present studies was to investigate (1) prevention of hepatic reperfusion injury after warm ischemia by administration of the antioxidant glutathione (GSH) and (2) whether GSH confers protection through influences on KC toxicity., Methods: Isolated perfused rat livers were subjected to 1 h of warm ischemia followed by 90 min of reperfusion without (n = 5) or with GSH or catalase (n = 4-5 each). Selective KC activation by zymosan (150 micro g/ml) in continuously perfused rat livers was used to investigate KC-related liver injury., Results: Postischemic infusion of 0.1, 0.5, 1.0 and 2.0 mM GSH, but not 0.05 mM GSH prevented reperfusion injury after warm ischemia as indicated by a marked reduction of sinusoidal LDH efflux by up to 83 +/- 13% (mean +/- SD; p < 0.05) and a concomitant significant improvement of postischemic bile flow by 58 +/- 27% (p < 0.05). A similar protection was conveyed by KC blockade with gadolinium chloride indicating prevention of KC-related reperfusion injury by postischemic GSH treatment. Postischemic treatment with catalase (150 U/ml) resulted in a reduction of LDH efflux by 40 +/- 9% (p < 0.05). Accordingly, catalase as well as GSH (0.1-2.0 mM) nearly completely prevented the increase in LDH efflux following selective KC activation by zymosan in continously perfused rat livers., Conclusion: Postischemic administration of GSH protects the liver against reperfusion injury after warm ischemia. Detoxification of KC-derived hydrogen peroxide seem to be an important feature of the protective mechanisms., (Copyright 2002 S. Karger AG, Basel)

Background: We have recently shown that the transjugular intrahepatic portosystemic shunt (TIPS) is more effective than paracentesis in the treatment of cirrhotic patients with severe ascites and can prolong survival in selected patients. Although an improved quality of life (QOL) has been suggested in these patients after the TIPS procedure, so far there are no data available to substantiate this assumption. Therefore, the aim of this study was to determine the effect of TIPS on the QOL in cirrhotic patients with refractory or recidivant ascites., Methods: 21 cirrhotic patients who underwent TIPS for refractory or recidivant ascites were investigated. All patients were pretreated with repeated paracentesis for at least 1 year. Before the procedure and at 3 and 6 months during follow-up, the patients themselves rated QOL, fatigue and physical performance on a visual analogue scale (range 0-100). Furthermore, QOL was determined by the QOL index (range 0-10) according to Spitzer., Results: Patients' rating of the QOL on the visual analogue scale significantly increased from 35 +/- 25 (baseline) to 64 +/- 28 (3 months), and 66 +/- 24 (6 months; p = 0.02). Similarly, the QOL index significantly increased from 6.9 +/- 2.0 (baseline) to 8.3 +/- 2.1 (3 months), and 8.6 +/- 1.7 (6 months; p < 0.001). The increase of QOL was more pronounced in patients with complete response to TIPS., Conclusions: We demonstrate that TIPS for refractory or recidivant ascites improves the QOL in patients with cirrhosis. Our data indicates that this improvement is dependent on the response to therapy., (Copyright 2002 S. Karger AG, Basel)