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Biomedical subjects

A T Blei

Publications and source records attributed to A T Blei.

At least 19 recordsLinked to original sources
PubMed2001

Cerebral hyperemia and nitric oxide synthase in rats with ammonia-induced brain edema.

BACKGROUND/AIM: Brain edema is a common fatal complication in acute liver failure. It is related to an acute change in brain osmolarity secondary to the glial accumulation of glutamine. Since high cerebral blood flow (CBF) precedes cerebral herniation in fulminant hepatic failure we first determined if an increase in brain water and glutamine are prerequisite to a rise in CBF in a model of ammonia-induced brain edema. Secondly, we determined if such a cerebral hyperperfusion is mediated by nitric oxide synthase (NOS). METHODS: Male rats received an end-to-side portacaval anastomosis (PCA). At 24 h, they were anesthetized with ketamine and infused with ammonium acetate (55 microM/kg per min). Studies were performed at 60, 90, 120, 150 and 180 min after starting the ammonia infusion and once the intracranial pressure had risen three-fold (mean 210'). Brain water (BW) was measured using the gravimetry method and CBF with the radioactive microsphere technique. Glutamine (GLN) in the CSF was sampled via a cisterna magna catheter. The neuronal NOS was specifically inhibited by 1-2-trifluoromethylphenyl imidazole (TRIM, 50 mg/kg intraperitoneally) and in separate studies nonspecifically by N-omega-nitro-L-arginine (L-NNA, 2 microg/kg per min intravenously) RESULTS: At 90', brain water was significantly increased (P < 0.015) as compared to the 60' group while CBF was significantly different at 150'. A significant correlation was observed between values of CBF and brain water (r = 0.88, n = 36, P < 0.001). Administration of either TRIM or L-NNA did not prevent the development of cerebral hyperperfu. sion and edema. CONCLUSION: We observed that cerebral hyperemia follows an initial rise in brain water content, rather than in the cerebrospinal fluid concentration of glutamine. The rise in CBF further correlated with brain water accumulation and was of critical importance for the development of intracranial hypertension. The unique mechanism for the rise in CBF in hyperammonemia was not prevented by NOS inhibition indicating that NO is not the mediator of high CBF and intracranial hypertension.

Ammonia↗
PubMed2001

Pathophysiology of brain edema in fulminant hepatic failure, revisited.

We have proposed a combined osmolar-hemodynamic disturbance to explain the presence of brain edema in fulminant hepatic failure, a major cause of death in this disorder. The concept of an osmotic disturbance in the brain, emphasizing the presence of astrocyte swelling and low-grade cerebral edema, has been expanded to the entire spectrum of liver disease. The mechanism of cerebral hyperemia in patients with FHF and brain swelling has been studied in experimental models linking hyperammonemia and glutamine generation in astrocytes to the development of this hemodynamic alteration. Measures to control cerebral hyperemia, such as mild hypothermia, are effective in preventing the development of brain edema in experimental models as well as intracranial hypertension in human disease.

Brain Edema↗
PubMed2001

Monitoring of brain water by chemical shift imaging during ammonia-induced brain swelling in rats after portacaval anastomosis.

Brain edema is a leading cause of death in acute liver failure (ALF). In experimental models of ALF, an increase in the content of brain water has been inferred indirectly by measuring intracranial pressure or determined directly via analysis of brain tissue postmortem. In this study, noninvasive proton two-dimensional chemical shift imaging (2-D CSI) was used to follow the time course of the development of brain edema in a well characterized model, namely ammonium acetate infusion into rats 48 to 72 h after portacaval anastomosis (PCA). Clear differences between control and experimental rat brains were observed, with an increase of brain water signal only in the parietal cortex of the PCA + ammonia group. Selective swelling of the cerebral cortex points to a cytotoxic mechanism in the evolution of brain edema in this model. CSI signal enhancement was much greater than the gravimetrically determined water content increase. The significantly greater signal change observed with 2-D CSI may reflect enhanced proton density that results from increased water content as well as edema-related alterations in water relaxation times.

Ammonia↗
PubMed2001

Indomethacin prevents the development of experimental ammonia-induced brain edema in rats after portacaval anastomosis.

Patients with fulminant hepatic failure (FHF) die with brain edema, exhibiting an increased cerebral blood flow (CBF) at the time of cerebral swelling. Mild hypothermia prevents brain edema in experimental models and in humans with FHF, an effect associated with normalization of CBF. To study the effects of alterations of CBF on the development of brain edema, we administered intravenous (IV) indomethacin to rats receiving an ammonia infusion after portacaval anastomosis. This model predictably develops brain edema and a marked increase in CBF at 3 hours of infusion. Brain water was measured with the gravimetry technique; CBF was monitored with both laser Doppler flowmetry and radioactive microspheres, whereas intracranial pressure (ICP) was monitored with a cisterna magna catheter. Coadministration of indomethacin prevented the increase in CBF seen with ammonia alone (110 +/- 19% vs. -2 +/- 9%) as well as the increase in brain water (80.86 +/- 0.12% vs. 80.18 +/- 0.06%) and the increase in ICP. Plasma ammonia and brain glutamine levels were markedly elevated in the ammonia-infused group and unaffected by indomethacin. However, ammonia uptake by the brain was significantly reduced by indomethacin. Levels of 6-keto-PGF(1alpha), a stable metabolite of prostacyclin, were reduced in the cerebrospinal fluid (CSF) of indomethacin-treated animals. As with mild hypothermia, avoiding cerebral vasodilatation with indomethacin will prevent the development of brain edema in this hyperammonemic model. Cerebral vasoconstriction reduces cerebral ammonia uptake and, if selective to the brain, may be of benefit in FHF.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

Body mass index as a predictor of hepatic steatosis in living liver donors.

Evaluation of the living donor for liver transplantation is a complex process involving such invasive studies as liver biopsy and angiography. It is important to establish the likelihood and extent of hepatic steatosis in living donors by clinical, imaging, and biochemical parameters to avoid performing a liver biopsy, if possible. In this study, the predictive value of body mass index (BMI), liver chemistry tests, and imaging studies was compared with liver histological examination in 33 potential living donors. Patients were grouped and compared based on their BMI (<25, 25 to 28, >28). No patient with a BMI less than 25 had hepatic steatosis. Of patients with a BMI of 25 to 28, steatosis was found on biopsy in 3 of 9 patients. Thirteen of 17 patients (76%) with a BMI greater than 28 had hepatic steatosis on liver biopsy. There was a significant correlation between BMI and overall grade of steatosis (R = 0.49). All subjects with steatosis detected on magnetic resonance imaging (MRI) or computed tomography (CT) had steatosis on biopsy, and all but 2 such patients had greater than 10% steatosis on biopsy. Conversely, 30% of patients in the MRI group and 24% of patients in the CT group failed to show hepatic steatosis when it was present on biopsy. Thus, it appears that liver biopsy could be avoided in subjects with a normal BMI and absence of risk factors. Individuals with a high BMI should undergo liver biopsy because biochemical and imaging data are currently inadequate to determine the extent of steatosis. Future studies should aim at improving the sensitivity of imaging techniques in the diagnosis of steatosis.

Adolescent↗
PubMed2001

Hepatic Encephalopathy.

1. Acute Encephalopathy in Cirrhosis A. GENERAL MEASURES. Tracheal intubation in patients with deep encephalopathy should be considered. A nasogastric tube is placed for patients in deep encephalopathy. Avoid sedatives whenever possible. Correction of the precipitating factor is the most important measure. B. SPECIFIC MEASURES i. Nutrition. In case of deep encephalopathy, oral intake is withheld for 24-48 h and i.v. glucose is provided until improvement. Enteral nutrition can be started if the patient appears unable to eat after this period. Protein intake begins at a dose of 0.5 g/kg/day, with progressive increase to 1-1.5 g/kg/day. ii. Lactulose is administered via enema or nasogastric tube in deep encephalopathy. The oral route is optimized by dosing every hour until stool evacuation appears. Lactulose can be replaced by oral neomycin. iii. Flumazenil may be used in selected cases of suspected benzodiazepine use. 2. Chronic Encephalopathy in Cirrhosis i. Avoidance and prevention of precipitating factors, including the institution of prophylactic measures. ii. Nutrition. Improve protein intake by feeding dairy products and vegetable-based diets. Oral branched-chain amino acids can be considered for individuals intolerant of all protein. iii. Lactulose. Dosing aims at two to three soft bowel movements per day. Antibiotics are reserved for patients who respond poorly to disaccharides or who do not exhibit diarrhea or acidification of the stool. Chronic antibiotic use (neomycin, metronidazole) requires careful renal, neurological, and/or otological monitoring. iv. Refer for liver transplantation in appropriate candidates. For problematic encephalopathy (nonresponsive to therapy), consider imaging of splanchnic vessels to identify large spontaneous portal-systemic shunts potentially amenable to radiological occlusion. In addition, consider the combination of lactulose and neomycin, addition of oral zinc, and invasive approaches, such as occlusion of TIPS or surgical shunts, if present. Minimal or Subclinical Encephalopathy Treatment can be instituted in selected cases. The most characteristic neuropsychological deficits in patients with cirrhosis are in motor and attentional skills (60). Although these may impact the ability to perform daily activities, many subjects can compensate for these defects. Recent studies suggest a small but significant impact of these abnormalities on patients' quality of life (61), including difficulties with sleep (62). In patients with significant deficits or complaints, a therapeutic program based on dietary manipulations and/or nonabsorbable disaccharides may be tried. Benzodiazepines should not be used for patients with sleep difficulties.

Adult↗
PubMed2000

Current status of liver support systems.

The search for a support system for liver failure has been intensified. Methods currently being tested include those based on artificial support, on biological approaches (including extracorporeal liver perfusion and transplanted hepatocytes) as well as hybrid devices that combine artificial aspects with biological systems. Each of these three areas is undergoing fast technological and conceptual development. Controlled clinical trials are also under way.

Hemoperfusion↗
PubMed2000

Diagnosis and treatment of hepatic encephalopathy.

Hepatic encephalopathy arises from the combination of hepatocellular dysfunction and portal-systemic shunting. Encephalopathy is more prominent in advanced stages of liver cirrhosis and signals the presence of fulminant hepatic failure in patients with acute liver injury. As important as the extent of shunting is the presence of large spontaneous collaterals. Ammonia continues to be a leading toxin influencing brain function. Endogenous benzodiazepines and cytokines may contribute to one of ammonia's key effects in the brain: astrocyte swelling. The diagnosis of hepatic encephalopathy is a diagnosis of exclusion; the search for a precipitating factor should be started immediately in all cases of encephalopathy. The treatment of hepatic encephalopathy has three aims: decrease the nitrogenous load from the gut, improve the extra-intestinal elimination of ammonia and counteract central abnormalities of neurotransmission. The mainstay of treatment is directed at the colon. Newer approaches targeting the brain, such as flumazenil, have become available.

Electroencephalography↗
PubMed2000

Intrahepatic portal-hepatic venous anastomosis: a portal-systemic shunt with neurological repercussions.

Intrahepatic shunts are rarely diagnosed as a cause of neurocognitive abnormality. A complaint of fatigue led to the diagnosis of a right portal vein-hepatic vein aneurysmal communication in a 23-yr-old, otherwise healthy woman. Neuropsychological testing, imaging, and MR spectroscopy revealed changes similar to those described in patients with cirrhosis and subclinical hepatic encephalopathy. T1-weighted MRI showed a hyperintense globus pallidus, a feature seen in subjects with and without portal-encephalopathy. Portal-systemic shunting in the absence of parenchymal liver disease reproduces neurological features described in cirrhosis.

Adult↗
PubMed2000

Intensive care management of patients with acute liver failure with emphasis on systemic hemodynamic instability and cerebral edema: a critical appraisal of pathophysiology.

Acute liver failure (ALF) is a devastating disease leading to multiorgan dysfunction. The most dramatic impact of ALF is on the brain, as hepatic encephalopathy and intracranial hypertension (IH) develop. IH is associated with systemic hemodynamic instability, alterations in the regulation of cerebral blood flow and the development of cerebral edema. This review focuses on the pathophysiology of IH with special emphasis on cerebral blood flow and the development of cerebral edema. Based on these considerations, both traditional and new treatments for the management of IH in the future are discussed.

Brain↗
PubMed1999

Cerebral blood flow and the development of ammonia-induced brain edema in rats after portacaval anastomosis.

Two mechanisms may account for brain edema in fulminant hepatic failure: the osmotic effects of brain glutamine, a product of ammonia detoxification, and a change of cerebral blood flow (CBF). We have shown brain edema, a marked increase in brain glutamine, and a selective rise in CBF in rats after portacaval anastomosis receiving an ammonia infusion. In this study, we inhibited the activity of glutamine synthetase with methionine-sulfoximine (MSO) and examined ammonia levels, brain water and CBF. Four groups received either a continuous ammonium acetate or control infusion; half of the animals had been pretreated with MSO or vehicle. The ammonia group exhibited brain edema (79.97 +/- 0.04 vs. 81.11 +/- 0. 13% water), an increase in cerebrospinal fluid (CSF) glutamine (1.29 +/- 0.21 vs. 2.84 +/- 0.39 mmol/L) and CBF (63 +/- 11 vs. 266 +/- 45 mL/min/100 g brain). When MSO was added to the ammonia infusion, ammonia levels rose further (928 +/- 51 vs. 1,293 +/- 145 mmol/L, P <.05) but CSF glutamine decreased (2.84 +/- 0.39 vs. 1.61 +/- 0.2 mmol/L, P <.01). Brain edema (80.48 +/- 0.11%) and cerebral hyperemia (140 +/- 25 mL/min/100 g brain) were significantly ameliorated in the ammonia plus MSO group. Brain output of circulating nitric oxide (NO(x)) was increased in the ammonia-infused group but normalized in the ammonia plus MSO group. In this model, the rise of CBF reflects intracranial events that occur after glutamine synthesis. Activation of nitric oxide synthase in the brain could account for these findings.

Ammonia↗