Hepatic ischaemia-reperfusion injury from bench to bedside.

BACKGROUND: Vascular occlusion to prevent haemorrhage during liver resection causes ischaemia-reperfusion (IR) injury. Insights into the mechanisms of IR injury gathered from experimental models have contributed to the development of therapeutic approaches, some of which have already been tested in randomized clinical trials. METHODS: The review was based on a PubMed search using the terms 'ischemia AND hepatectomy', 'ischemia AND liver', 'hepatectomy AND drug treatment', 'liver AND intermittent clamping' and 'liver AND ischemic preconditioning'; only randomized controlled trials (RCTs) were included. RESULTS: Twelve RCTs reported on ischaemic preconditioning and intermittent clamping. Both strategies seem to confer protection and allow extension of ischaemia time. Fourteen RCTs evaluating pharmacological interventions, including antioxidants, anti-inflammatory drugs, vasodilators, pharmacological preconditioning and glucose infusion, were identified. CONCLUSION: Several strategies to prevent hepatic IR have been developed, but few have been incorporated into clinical practice. Although some pharmacological strategies showed promising results with improved clinical outcome there is not sufficient evidence to recommend them.

Experimental models of temporary normothermic liver ischemia.

Hepatic ischemia/reperfusion injury has so far been investigated in various experimental models. A clinical transfer of experimental results is, however, problematic because of anatomical and physiological differences and also the inevitable simplification of experimental work. The choice of model must therefore be adapted to the clinical question to be answered. The simplest procedure for inducing normothermic ischemia is to clamp the hepatoduodenal ligament. Models that do not avert portal congestion are regarded as unsuitable. Our current understanding of the pathogenesis of ischemia/reperfusion injury depends mainly on studies whose authors have investigated either global liver ischemia with a portocaval shunt, spleen transposition and in the isolated perfused system, or partial ischemia. This review is a critical examination of various approaches to the study of normothermic hepatic ischemia in experimental animals.

Development and evaluation of an experimental model for investigating the pathogenesis and therapeutic strategies of acute liver failure.

Because of the various etiologies of acute liver failure (ALF) a clinically relevant model must fulfill four criteria--reversibility, reproducibility, ALF-induced death, and a sufficient time interval for diagnosis and therapy between induction and death. In this study an experimental model was evaluated for these criteria. A total of 49 rats were randomized into seven groups: First, a pilot study was performed regarding the survival rate after different treatments: In group I, animals underwent a 70% liver resection. In group II, 70% liver resection was combined with ascending doses of postoperative endotoxin administration up to 400 microg/kg (group IIc). In group III, animals only underwent liver mobilization. In group IV, ALF was induced according to the protocol of group IIc, but with additional treatment of an endothelin-A-receptor (ETAR) antagonist. Animals in group V received only 400 microg endotoxin. After induction of ALF, all animals died within the first day, showing significantly elevated bilirubin and ammonium levels and severe damage to hepatocellular integrity. Application of the ETAR antagonist resulted in the survival of 6/7 animals until the 14th day; the biochemical and histomorphological changes were reversible. All other animals survived to the 14th day. A clinically relevant model of ALF in rats can be created by the combination of 70% liver resection and endotoxin application to produce an inflammatory component.

Antibiotic prophylaxis at urinary catheter removal prevents urinary tract infection after kidney transplantation.

BACKGROUND: Urinary tract infections (UTI) are common nosocomial infections in kidney transplant recipients, with limited evidence to guide antibiotic prophylaxis at urinary catheter removal. The aim of our study was to evaluate the effect of short-term antibiotic therapy at the moment of catheter removal after kidney transplantation. METHODS: Twenty kidney transplant recipients received 250 mg of ciprofloxacin orally twice daily 1 day before and at the day of the removal of the urinary catheter and were compared with 20 kidney transplant recipients without prophylaxis. UTI was diagnosed by use of urine culture and clinical signs. RESULTS: All patients were comparable in sex, age, etiology of end-stage renal failure, immunosuppression, donor type, and initial function. After catheter removal at the 6th postoperative day, a rapid rise of UTI in kidney transplant recipients without prophylaxis (n = 12, 60%) was observed, whereas in patients with antibiotic prophylaxis the rate of UTI could be significantly reduced to 20%. Escherichia coli was the most isolated pathogen in the patients with UTI and was detected at the catheter tip in more than 50% of cases. In 2 patients (10%) after antibiotic prophylaxis, a ciprofloxacin-resistant E coli strain was detected. CONCLUSIONS: The use of antibiotic prophylaxis during urinary catheter removal is recommended to prevent UTI in kidney transplant recipients.

Gender and strain-specific differences in the development of steatosis in rats.

Non-alcoholic fatty liver disease (NAFLD) is a common problem with a wide variety of phenotypes. While its pathogenesis is still not fully understood, several risk factors for disease progression have been identified. Therefore, defining adequate animal models may serve to unreveal the pathogenesis in NAFLD. We studied Lewis and Sprague-Dawley rats of both genders (n = 6) fed standard (Std) or high-fat (HF) diet for three weeks. Disease stage was assessed by haematoxylin-eosin, Azan Heidenheim and Oil-Red staining, apoptosis by single-stranded DNA (ssDNA) detection and liver regeneration by Ki-67 staining. Serum markers of liver injury and lipid metabolism including adipocytokines were analysed. Livers of both strains and genders fed with HF diet demonstrated evidence of steatosis. Lewis rats developed microvesicular steatosis whereas Sprague-Dawley rats presented macrovesicular steatosis accompanied by pronounced fibrosis. Female gender of both strains was associated with lower steatosis grade and higher proliferation rate (P < 0.05). Gender-specific differences were most prominent in Lewis rats on a HF diet, where females showed lower alkaline phosphatase, cholesterol, triglyceride and leptin levels and a more favourable low-density lipoprotein/high-density lipoprotein ratio than males (P < 0.05). Reverse transcriptase-polymerase chain reaction analysis was performed to demonstrate changes in expression of various genes important for liver regeneration, fibrosis and steatosis. HF diet induced downregulation of proangiogenic genes such as vascular endothelial growth factor receptor 1 and 2 (P < 0.05) in males was not present in females. In conclusion, strain and gender served major roles in disease progression. These differences should be considered when designing studies and may offer new ways to advance therapeutic strategies.