Graft Neutrophil Sequestration and Concomitant Tissue Plasminogen Activator Release During Reperfusion in Clinical Kidney Transplantation.

BACKGROUND: Inflammation, coagulation, and fibrinolysis are tightly linked together. Reperfusion after transient ischemia activates both neutrophils, coagulation, and fibrinolysis. Experimental data suggest that tissue plasminogen activator (tPA) regulates renal neutrophil influx in kidney ischemia and reperfusion injury. METHODS: In 30 patients undergoing kidney transplantation, we measured renal neutrophil sequestration and tPA release from blood samples drawn from the supplying artery and renal vein early after reperfusion. tPA antigen levels were measured using a commercial enzyme-linked immunosorbent assay kit. For each parameter, transrenal difference (Δ) was calculated by subtracting the value of the arterial sample (ingoing blood) from the value of the venous sample (outgoing blood). RESULTS: Positive transrenal gradients of tPA antigen occurred at 1 minute [Δ = 14 (3-46) ng/mL, P < .01] and 5 minutes [Δ = 5 (-3 to 27) ng/mL, P < .01] after reperfusion. At 5 minutes after reperfusion, a negative transrenal gradient of neutrophils was observed [Δ = -0.17 (-1.45 to 0.24) x 10E9 cells/L, P < .001]. At 1 minute after reperfusion, neutrophil sequestration into the kidney (ie, negative transrenal neutrophil count) correlated significantly with tPA release from the kidney (ie, positive transrenal tPA concentration), (R = -0.513 and P = .006). CONCLUSIONS: The findings suggest a proinflammatory role for tPA in ischemia and reperfusion injury in human kidney transplantation.

Enhanced recovery protocol after liver resection.

BACKGROUND: Enhanced recovery protocols (ERPs) accelerate patient recovery and shorten hospital stay by optimization of perioperative care. However, experience with ERPs is still limited in liver surgery. METHODS: The implementation of a multimodal ERP was studied in patients who underwent open and laparoscopic liver surgery. An opioid-sparing pain treatment was chosen together with early mobilization and oral feeding, as well as restricted use of abdominal drains and catheters. Date to discharge, postoperative complications and patient satisfaction were assessed. A historical cohort of patients who underwent liver resection served as a control group. RESULTS: Some 134 liver resections (126 open, 8 laparoscopic) were performed between April 2013 and March 2014. Operations were carried out mostly for malignant liver tumours. One hundred and six (79.1 per cent) of the 134 patients were discharged by the fifth postoperative day. The median (range) postoperative hospital stay was 4 (2-11) days, compared with 6 (4-16) days for the control group (P < 0.001). Only four patients in the ERP group were readmitted and the 30-day mortality rate was zero. CONCLUSION: An ERP for perioperative care after liver surgery was introduced safely and effectively. Discharge within 4 days is achievable with no increase in adverse events and good patient satisfaction.

Bridging therapies and liver transplantation in acute liver failure, 10 years of MARS experience from Finland.

Acute liver failure is a life-threatening condition in the absence of liver transplantation option. The aetiology of liver failure is the most important factor determining the probability of native liver recovery and prognosis of the patient. Extracorporeal liver assist devices like MARS (Molecular Adsorbent Recirculating System) may buy time for native liver recovery or serve as bridging therapy to liver transplantation, with reduced risk of cerebral complications. MARS treatment may alleviate hepatic encephalopathy even in patients with a completely necrotic liver. Taking this into account, better prognostic markers than hepatic encephalopathy should be used to assess the need for liver transplantation in acute liver failure.

Hepatic neutrophil activation during reperfusion may not contribute to initial graft function after short cold ischemia in human liver transplantation.

BACKGROUND: Experimental models of hepatic ischemia/reperfusion injury have implicated a pathophysiologic role for neutrophils in subsequent hepatocellular damage. In human liver transplantation, however, the effect of reperfusion-induced neutrophil activation on initial graft function is not clear. METHODS: In 38 patients undergoing liver transplantation, neutrophil CD11b and L-selectin expression, neutrophil count, and plasma lactoferrin levels were measured. To assess changes within the graft during initial reperfusion, samples of blood entering and leaving the graft were obtained simultaneously, and transhepatic ratio calculated (hepatic vein/portal vein; 1 denotes no change, <1 a decrease, and >1 an increase across the liver). Graft steatosis, postoperative liver function, and outcome were recorded. Associations between neutrophil activation markers and outcome measures were evaluated. RESULTS: Substantial hepatic neutrophil activation occurred during initial reperfusion, demonstrated by concomitant L-selectin shedding and CD11b upregulation (transhepatic ratios 0.9 [0.7-1.0]; 1.4 [0.9-1.9]; both P < .001; portal vs hepatic vein]. Simultaneously, hepatic neutrophil sequestration and lactoferrin release occurred (0.3 [0.2-0.5]; 1.7 [1.3-3.4]; both P < .001). Neither cold ischemic time (CIT; median 5 hours 36 minutes) nor hepatic neutrophil activation during reperfusion predicted early graft function, nor was there any association between CIT and neutrophil activation. CONCLUSIONS: Despite short CIT, extensive graft neutrophil activation and sequestration occurred. This, however, was not associated with impaired early graft function, suggesting short CIT may protect against severe neutrophil-mediated injury.