Protein S-100β: A biochemical marker for increased intracranialpressure in pigs with acute hepatic failure

Ytrebø, L.M.; Ingebrigtsen, Tor; Nedredal, GI; Elvenes, Odd Petter; Korvald, Christian; Romner, Bertil; Revhaug, A.

doi:10.1016/s0168-8278(00)80568-1

Cited by 16 publications

(30 citation statements)

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“…The pigs were kept in the animal department for at least 2 days before the experiments. Details regarding the animal room facilities, anesthesia, and surgical preparation have been previously reported (47)(48)(49). Briefly, the pigs underwent a tracheotomy, were intubated, and ventilated on a volume-controlled respirator (Servo 900; Elema-Schnander, Stockholm, Sweden).…”

Section: Methodsmentioning

confidence: 99%

Nitric oxide and l-arginine metabolism in a devascularized porcine model of acute liver failure

Sharma

Have

Ytrebø

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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In acute liver failure (ALF), the hyperdynamic circulation is believed to be the result of overproduction of nitric oxide (NO) in the splanchnic circulation. However, it has been suggested that arginine concentrations (the substrate for NO) are believed to be decreased, limiting substrate availability for NO production. To characterize the metabolic fate of arginine in early-phase ALF, we systematically assessed its interorgan transport and metabolism and measured the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) in a porcine model of ALF. Female adult pigs (23-30 kg) were randomized to sham (N ϭ 8) or hepatic devascularization ALF (N ϭ 8) procedure for 6 h. We measured plasma arginine, citrulline, ornithine levels; arginase activity, NO, and ADMA. Whole body metabolic rates and interorgan flux measurements were calculated using stable isotope-labeled amino acids. Plasma arginine decreased Ͼ85% of the basal level at t ϭ 6 h (P Ͻ 0.001), whereas citrulline and ornithine progressively increased in ALF (P Ͻ 0.001 and P Ͻ 0.001, vs. sham respectively). No difference was found between the groups in the whole body rate of appearance of arginine or NO. However, ALF showed a significant increase in de novo arginine synthesis (P Ͻ 0.05). Interorgan data showed citrulline net intestinal production and renal consumption that was related to net renal production of arginine and ornithine. Both plasma arginase activity and plasma ADMA levels significantly increased in ALF (P Ͻ 0.001). In this model of early-phase ALF, arginine deficiency or higher ADMA levels do not limit whole body NO production. Arginine deficiency is caused by arginase-related arginine clearance in which arginine production is stimulated de novo.arginine; asymmetric dimethylarginine; arginase ACUTE LIVER FAILURE (ALF) is characterized by sudden and severe liver dysfunction with rapid progression to coagulopathy, encephalopathy, and multiorgan failure. Without liver transplantation, mortality from ALF is about 50% (4). A hallmark of ALF is the presentation of systemic hypotension and a hyperdynamic circulation (39). This is associated with increased guanylate cyclase (GC) activation by nitric oxide (NO) (33), which converts guanidine triphosphate to cyclic guanidine monophosphate and is thought to cause the vasodilatation seen in ALF (34). Previously, we have reported the characteristics of the same devascularized porcine liver model of ALF, which was shown to have a hyperdynamic circulation as evidenced by a high cardiac output and low mean arterial pressure and systemic vascular resistance (50). However, in this hyperacute model of ALF, no significant changes in the metabolites of NO were observed. Indeed, the kinetics of NO in this model and whether it is involved in the initiation of the vasodilation of ALF remain unknown.L-Arginine has several important biological functions (2, 3, 5), one of which is to be the nitrogen-donating substrate for endothelial NO synthase (eNOS) to produce NO and citrulline in stoichiometric quantities (...

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Section: Methodsmentioning

confidence: 99%

Nitric oxide and l-arginine metabolism in a devascularized porcine model of acute liver failure

Sharma

Have

Ytrebø

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…In the first, efforts to prevent the development of brain edema will be carried out in subjects with no (or mild) encephalopathy. Prediction of the development of brain edema may be improved by the serum assay of brain-derived proteins, such as astroglial S-100 45 and neuron-specific enolase. 46 Once brain edema and intracranial hypertension are present, the ability to influence the neurologic picture with medical therapy is reduced and a greater role for artificial/bioartificial methods will arise.…”

Section: A Glimpse Into the Futurementioning

confidence: 99%

Medical Therapy of Brain Edema in Fulminant Hepatic Failure

Blei

2000

Hepatology

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“…Following eight hours of liver devascularisation, this porcine model reveals typical clinical and biochemical features of ALF such as hyperammonemia, increased brain edema and intracranial hypertension [12][13][14][15], which are considered essential for studying neuropathological changes in the brain in relation to ALF. The major findings in our study were: (1) vasogenic brain edema is an important pathophysiological component associated with intracranial hypertension and (2) evidence of severe brain injury including edema, cellular swelling and necrotic cell death (neurons and astrocytes).…”

Section: Discussionmentioning

confidence: 99%

“…We have previously described a porcine model of ALF, induced by hepatic devascularization, which is associated with typical clinical and biochemical features of ALF including acute hyperammonemia, increased brain water and intracranial hypertension [12][13][14][15][16][17]. The aim of the present study was to use this large animal model to examine ultrastructural changes in the frontal lobe, cerebellum and brain stem in pigs with ALF.…”

Section: Introductionmentioning

confidence: 99%

Neuropathological changes in the brain of pigs with acute liver failure

Kristiansen

Lindal

Myreng

et al. 2010

Scandinavian Journal of Gastroenterology

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Kristiansen, R.G. et al., 2010. Neuropathological changes in the brain of pigs with acute liver failure. Scandinavian journal of gastroenterology, 45(7-8) ABSTRACTObjective. Cerebral edema is a serious complication of acute liver failure (ALF), which may lead to intracranial hypertension and death. An accepted tenet has been that the blood-brain barrier is intact and that brain edema is primarily caused by a cytotoxic etiology due to hyperammonemia. However, the neuropathological changes in ALF have been poorly studied. Using a well characterized porcine model we aimed to investigate ultrastructural changes in the brain from pigs suffering from ALF. Materials and methods. Sixteen female Norwegian Landrace pigs weighing 27-35 kg were randomised into two groups: ALF (n = 8) and sham operated controls (n = 8). ALF was induced with an end-to-side portacaval shunt followed by ligation of the hepatic arteries. Biopsies were harvested from three different areas of the brain (frontal lobe, cerebellum, and brain stem) following eight hours of ALF and analyzed using electron microscopy. Results. Profound perivascular and interstitial edema were found in all three areas. Disruption of pericytic and astrocytic processes were seen, reflecting breakdown/lesion of the blood-brain barrier in animals suffering from ALF. Furthermore, neurons and axons were edematous and surrounded by vesicles. Severe damage to Purkinje neuron (necrosis) and damaged myelin were seen in the cerebellum and brain stem, respectively. Biopsies from sham operated animals were normal. Conclusions. Our data support the concept that vasogenic brain edema plays an important role in the development of intracranial hypertension in pigs with ALF.

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Protein S-100β: A biochemical marker for increased intracranialpressure in pigs with acute hepatic failure

Cited by 16 publications

References 0 publications

Nitric oxide and l-arginine metabolism in a devascularized porcine model of acute liver failure

Nitric oxide and l-arginine metabolism in a devascularized porcine model of acute liver failure

Medical Therapy of Brain Edema in Fulminant Hepatic Failure

Neuropathological changes in the brain of pigs with acute liver failure

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