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Background: Postreperfusion syndrome and haemodynamic instability are predictors for poor outcome after liver transplantation. Cytokine release has been claimed to be responsible for postreperfusion syndrome. However, the underlying pathophysiologic mechanism is not clarified. The aim of this prospective observational study was to correlate cardiac performance (measured by transoesophageal echocardiography (TEE), Doppler and Tissue Doppler Imaging (TDI)) to plasmatic cytokines: IL-6, IL-8, CXCL1, TGF-β and CD40L at 5 different time points during liver transplantation., Methods: Seventeen consecutive patients scheduled for orthotopic liver transplantation, age 18 to 75 years without contraindication for transoesophageal echocardiography were included. Patients were monitored with TEE and TDI. Systolic and diastolic cardiac function, MAP, MPAP, CVP, PCWP, CO and blood samples for cytokine assays were recorded or collected after induction, 15 min after vena cava inferior clamping, 2 to 5 min after reperfusion, 60 min after reperfusion and at the end of surgery., Results: Mean arterial pressure and catecholamine requirements remained unchanged, MPAP, CVP and CO increased, SVR decreased after unclamping. Postreperfusion syndrome did not develop. The haemodynamic parameters and the variations of TEE parameters were consistent with the volume load changes during clamping and declamping and did not reveal systolic or diastolic cardiac dysfunction. All cytokines, except TGF-β, increased., Conclusion: These findings suggest, that significant cytokine release during liver transplantation is not necessarily coincident with haemodynamic instability and impaired cardiac function., Trial Registration: ClinicalTrials.gov: NCT00547924.

Abstract Background Thoracic surgery mandates usually a one-lung ventilation (OLV) strategy with the collapse of the operated lung and ventilation of the non-operated lung. These procedures trigger a substantial inflammatory response. The aim of this study was to analyze the cytokine and chemokine reaction in both lungs, pleural space and blood in patients undergoing lung resection with OLV with special interest in the chemokine growth-regulated peptide alpha (GROα) which is the human equivalent to the rat cytokine-induced neutrophil chemoattractant-1 (CINC-1). Methods Broncho-alveolar lavage (BAL) fluid of both the collapsed, operated and the ventilated, non-operated lung, respectively, pleural space drainage fluid and blood was collected and the concentrations of interleukin (IL)-6, IL-1RA and GROα were determined with enzyme-linked immunosorbent assays in 15 patients. Results Substantial inter-individual differences in the BAL fluid between patients in cytokine and chemokine levels occurred. In the pleural fluid and the blood these inter-individual differences were less pronounced. Both sides of the lung were affected and showed a significant increase in IL-6 and IL-1RA concentrations over time but not in GROα concentrations. Except for IL-6, which increased more in the collapsed, operated lung, no difference between the collapsed, operated and the ventilated, non-operated lung occurred. In the blood, IL-6 and IL-1RA increased early, already at the end of surgery. GROα was not detectable. In the pleural fluid, both cytokine and chemokine concentrations increased by day one. The increase was significantly higher in the pleural fluid compared to the blood. Conclusion The inflammatory response of cytokines affects both the collapsed, operated and the ventilated, non-operated lungs. The difference in extent of response underlines the complexity of the inflammatory processes during OLV. In contrast to the cytokines, the chemokine GROα concentrations did not react in the BAL fluid or in the blood. This indicates that GROα might not be useful as marker for the inflammatory reaction in complex surgical procedures.

Background: Tissue hypoperfusion and inflammation in sepsis can lead to organ failure including kidney and liver. In sepsis, mortality of acute kidney injury increases by more than 50%. Which type of volume replacement should be used is still an ongoing debate. We investigated the effect of different volume strategies on inflammatory mediators in kidney and liver in an early sepsis model. Material and Methods: Adult male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP) and assigned to three fluid replenishment groups. Animals received 30mL/kg of Ringer’s lactate (RL) for 2h, thereafter RL (75mL/kg), hydroxyethyl starch (HES) balanced (25mL/kg), containing malate and acetate, or HES saline (25mL/kg) for another 2h. Kidney and liver tissue was assessed for inflammation. In vitro rat endothelial cells were exposed to RL, HES balanced or HES saline for 2h, followed by stimulation with tumor necrosis factor-α (TNF-α) for another 4h. Alternatively, cells were exposed to malate, acetate or a mixture of malate and acetate, reflecting the according concentration of these substances in HES balanced. Pro-inflammatory cytokines were determined in cell supernatants. Results: Cytokine mRNA in kidney and liver was increased in CLP animals treated with HES balanced compared to RL, but not after application of HES saline. MCP-1 was 3.5fold (95% CI: 1.3, 5.6) (p<0.01) and TNF-α 2.3fold (95% CI: 1.2, 3.3) (p<0.001) upregulated in the kidney. Corresponding results were seen in liver tissue. TNF-α-stimulated endothelial cells co-exposed to RL expressed 3529±1040pg/mL MCP-1 and 59±23pg/mL CINC-1 protein. These cytokines increased by 2358pg/mL (95% CI: 1511, 3204) (p<0.001) and 29pg/ml (95% CI: 14, 45) (p<0.01) respectively when exposed to HES balanced instead. However, no further upregulation was observed with HES saline. PBS supplemented with acetate increased MCP-1 by 1325pg/mL (95% CI: 741, 1909) (p<0.001) and CINC-1 by 24pg/mL (95% CI: 9, 38) (p<0.01) compared to RL. Malate as well as HES saline did not affect cytokine expression. Conclusion: We identified HES balanced and specifically its component acetate as pro-inflammatory factor. How important this additional inflammatory burden on kidney and liver function is contributing to the sepsis-associated inflammatory burden in early sepsis needs further evaluation. [ABSTRACT FROM AUTHOR]

Background Although sevoflurane (Sevo) had been shown to ameliorate posttransplant injury in various organs, data available are inconsistent, particularly in the context of lung transplantation (Tx). We here investigated if preconditioning by Sevo can protect from posttransplant injury regarding both, primary graft dysfunction (PGD) and acute rejection (AR) after experimental lung Tx, thereby focusing on two important clinical outcome parameters. Materials and methods Three experimental approaches were used: (1) BALB/c mice were preconditioned for 2 h with Sevo or a fentanyl cocktail (Control; n = 10); (2) syngeneic (Syn) mouse lung Tx (C57BL/6) with a Sevo-preconditioned graft followed by 18 h storage to mimic PGD (Syn-Tx, n = 12) versus controls (fentanyl cocktail); and (3) allogeneic (Allo) Tx (BALB/c, donor; C57BL/6, recipient) to mimic AR (Allo-Tx, n = 12) versus controls (fentanyl cocktail). Syn-Tx grafts were harvested on Day 1, Allo-Tx grafts on Day 3 and analyzed for histology, immunohistochemistry, blood gas analysis, and inflammatory cytokines (enzyme-linked immunosorbent assay or reverse transcription polymerase chain reaction). Results Evaluating the preconditioning effect of Sevo only showed significantly better oxygenation ( P = 0.03) and a tendency toward lower levels of lung tissue messenger RNA for tumor necrosis factor-α. In Syn-Tx recipients, the Sevo group had histologically a tendency toward an attenuation of PGD and showed significantly lower levels of interleukin 6 ( P = 0.01) in plasma, but higher levels of interleukin 10 ( P < 0.01) in lungs. Allo-Tx grafts in Sevo Tx recipients showed attenuated AR with histologically significantly lower rejection scores ( P = 0.03), fewer classical macrophages (F4/80+; P < 0.01), but more anti-inflammatory activated macrophages (M2, CD206+; P < 0.01). Functionally, the Sevo group had a tendency toward improved oxygenation. Conclusions We demonstrated that Sevo preconditioning has protective effects on lung transplants in both, PGD and AR. The observed amelioration may be attributed to suppressed inflammatory cytokines during PGD and the induction of alternatively activated macrophages during AR. These promising data could set the base for using Sevo preconditioning in donor lungs for a human trial. [ABSTRACT FROM AUTHOR]