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PubMed1990

Ammonia and monoamine concentrations in two brain areas in rats after one hyperoxic seizure.

Monoamines (catecholamines, serotonin, and metabolites) and ammonia were studied within two areas of the rat brain--the frontal cortex (FC) and the striatum (SA)--after exposure to hyperbaric oxygen (HBO) at 6 ATA up to the first seizure. An increase of norepinephrine (NE), dopamine (DA), and metabolites (HVA, DOPAC) measured by the HPLC/EC method were found in SA with a parallel increase of ammonia at variance with the FC where no monoamine changes, but a slight increase of ammonia, were found. Blood ammonia did not change with HBO. So, 20 min after one HBO seizure, there are regional differences in the brain, which are consistent with the previous findings of an SA start of electrocortical abnormalities at the onset of a seizure. Elevated DA, and possibly NE, levels may contribute to the accumulation of ammonia in the brain. During prolonged HBO exposure, this rise of ammonia could be one of the mechanisms involved in the relapse of seizures. It might also be implicated in initiation of the first seizure. By their situations and contents, SA glial cells could play an important role in brain HBO susceptibility.

Ammonia↗
PubMed1986

[Dynamics of ammonia and pH in meat stored under various conditions].

The changes in ammonia content and pH values in beef and pork stored at different temperatures were studied in relation with sensory changes. Samples were taken from the stored meat at a temperature of +3 degrees C in the 0th, 12th, 36th, 60th, 84th, 108th and 132nd hour and at a temperature of +10 degrees C in the 0th, 6th, 24th, 36th, 54th, 72nd and 84th hour. The quantity of ammonia in the samples was determined by means of an ion-selective electrode. The pH value was determined potentiometrically. The kinds of meat (pork, beef) differed in the development of ammonia content. Ammonia content was found to be directly dependent on storage temperature. A similar relation was observed in the development of pH values. The sensory changes of stored meat were parallel to the changes in ammonia levels and pH values. The results can be used for an evaluation of the degree of biochemical changes in the meat and of the fitness of the raw material to the production of tins for long storage. Advantageous points are seen in the rapid and objective determination of ammonia content by the ion-selective electrode and the determination of the pH value by means of the combined glass electrode with the aid of the same apparatus.

Ammonia↗
PubMed1988

[Dynamics in ammonia levels in the process of producing canned meat for long-term storage].

Ammonia contents were studied in correlation with sensory changes in raw materials (pork and beef) used for the production of meat cans, and in relation to sensory changes at the end of their production. The following three types of meat cans designed for long-term storage were tested: Pork in Natural Juice, Beef with Bacon, and Luncheon Meat. Raw materials used for the production of meat cans had the known sensory characteristics and known ammonia values. Four groups of final products were prepared from each kind of these meat cans; the materials used for this purpose differed in their freshness. To obtain these differences in freshness, the material had been stored under constant conditions (average temperature 12.5 degrees, relative humidity 78.0%) and processed step by step in four work shifts during two days in succession. Each kind of raw material was sampled before processing into the final product and the samples of canned meat were taken after the termination of the technological process of production. The samples were subjected to sensory evaluation and the quantitative content of ammonia was determined in all of them by a microdiffusion method. In all kinds of meat the contents of ammonia evidently increased with the time of storage whereas the values of sensory evaluation declined. As indicated by measurements during the technological process of production, sterilization increases the ammonia content. The value of ammonia content in the meat cans at the end of the technological process of production indicates how fresh is the raw material. In combination with other investigations, this value can be used for forecasting the changes in canned meat in the course of long-term storage.

Ammonia↗
PubMed1987

Ammonia kinetics in eight patients with liver disease and in dogs.

Pharmacokinetic parameters of ammonia were calculated from a constant-rate infusion of ammonium chloride in 8 patients with chronic liver disease, and in 19 healthy mongrel dogs. In the animal group, the median half-life of the infused ammonia was approximately 4 minutes (range 3.5-5 minutes). The median ammonia clearance was 4.4 l/min (range 3.3-9.2 l/min). The median volume of distribution was approximately 28 liters. In the animal group, the median half-life of the infused ammonia was one minute (range less than 1-4 minutes). The median clearance was 2.2 l/min (range 1.2-4.2 l/min). The median volume of distribution was 3.1 liters. The short half-life and the high clearance of ammonia underscore the importance of the extrahepatic ammonia removal mechanisms.

Ammonia↗
PubMed1985

[Positron computed tomography for myocardial uptake of N-13 ammonia in patients with hypertrophic cardiomyopathy: a preliminary study].

In the present study, positron computed tomography (PCT) was used to evaluate the myocardial uptake of N-13 ammonia in patients with hypertrophic cardiomyopathy (HCM). Eight subjects including two normal persons, four patients with HCM, and two with old myocardial infarction (OMI) were selected for the study. N-13 ammonia was administered intravenously as a bolus and, commencing with the tracer injection, serial 30-second PCT scans were performed. The results were summarized as follows: The first scan exhibiting cardiac blood pool images revealed a reduced left ventricular cavity in the HCM subjects. After clearance of N-13 from the cardiopulmonary vasculature, the left ventricular myocardium was clearly visualized and an increased myocardial mass with characteristic morphology was demonstrated in the HCM subjects. Detailed analysis of the time-activity curves of the blood pool and myocardium derived from these serial scan images disclosed two uptake phases in the uptake mode of N-13 ammonia. In the initial phase within three minutes, the myocardial uptake of N-13 was rapid in the normal and OMI subjects, whereas its significant delay was observed in the HCM subjects. This may reflect an abnormal initial extraction of N-13 ammonia in the HCM patients compared with the other subjects. Subsequently, in the second phase, which was characterized by a gradual increase of N-13 in the myocardium, the HCM subjects revealed higher uptake ratios than did the others. This may indicate an increased extraction of metabolites of N-13 ammonia during the second phase. These preliminary results underscore the usefulness of dynamic PCT with N-13 ammonia for the assessment of HCM.

Adult↗
PubMed1984

Brain methanethiol and ammonia concentrations in experimental hepatic coma and coma induced by injections of various combinations of these substances.

In normal rats in a coma induced by NH+4 alone or by methanethiol alone, the brain and blood levels of ammonia or methanethiol are much higher than those observed in rats in experimental hepatic coma. When various smaller dosage combinations of NH+4, methanethiol, and octanoic acid were injected simultaneously, coma occurred at lower brain and blood concentrations of ammonia and methanethiol. Brain ammonia and methanethiol concentrations in normal rats receiving 0.75 mmol NH+4 plus 0.15 mmol octanoic acid plus 18 mumol methanethiol were comparable with those observed in 24 rats in hepatic coma after fulminant hepatic failure caused by acute massive ischemic liver necrosis. The normal rats became comatose. In these rats and in the rats in hepatic coma, the ammonia level in the brain was increased threefold and the methanethiol level in the brain was increased fivefold. Because these levels of ammonia and methanethiol were sufficient to induce coma in normal rats, they should also have been sufficient to induce coma in rats with damaged livers. Therefore, the accumulation of ammonia and methanethiol in the central nervous system after the acute massive ischemic necrosis may have been sufficient to account for the coma that ensued, without the involvement of other factors.

Ammonia↗
PubMed1984

Influences of specimen processing and storage conditions on results for plasma ammonia.

Ammonia concentrations in plasma may increase because of contamination and deterioration of blood components during specimen handling and storage. Using replicate specimens from healthy volunteers, we studied influences of specimen processing and storage procedures on ammonia measurements made with a self-contained reagent system. Under some conditions, ammonia concentrations more than doubled. The use of nonhemolyzed plasma specimens and prompt centrifugation, separation of plasma, and ammonia determination apparently were important in avoiding such increases, the duration of contact between plasma and cells being the most important factor. Lower temperatures had minimal effect on whole-blood storage and centrifugation, but retarded increases in ammonia in stored plasma. We conclude that procedures for collection and storage of specimens for ammonia determinations should be standardized and strictly observed.

Ammonia↗
PubMed1981

Effects of ammonia infusion on plasma glucagon, insulin, and amino acids in intact, pancreatectomized, and adrenalectomized dogs.

Ammonium salts were infused in intact, pancreatectomized, and adrenalectomized dogs to produce coma-inducing amounts of plasma ammonia. Changes in intact dogs included hyperglycemia, hyperglucagonemia, hyperinsulinemia, and decreases in plasma concentrations of glutamine, alanine, threonine, glycine, lysine, valine, proline, serine, arginine, leucine, isoleucine, and methionine. Urinary excretion of catecholamines increased more than 20-fold, whereas plasma hydrocortisone concentrations were essentially unchanged. In pancreatectomized dogs, ammonia infusions caused hyperglycemia, a mild hyperglucagonemia, and no changes in plasma amino acid concentrations, other than a decrease in alanine and an increase in taurine. In adrenalectomized dogs, ammonia infusion resulted in normoglycemia, hyperglucagonemia (comparable with that seen in intact dogs), hyperinsulinemia (2 to 3 times that seen in intact dogs), and decreased plasma concentrations of alanine, isoleucine, leucine, and valine. Finally, propranolol administration did not affect ammonia-induced glucagon and insulin release. The endocrine portion of the pancreas appears to mediate the major effects of ammonia on plasma amino acid values. The effect of ammonia in stimulating glucagon release may occur by an alpha-adrenergic pathway or by direct stimulation of pancreatic islet cells.

Adrenal Glands↗
PubMed1994

Ischemia produces an increase in ammonia output in swine myocardium.

We have recently reported that ischemia causes myocardial ammonia production which is not due to amino acid breakdown. The purpose of this study was to identify the remaining possible sources of ammonia production. The prospects were either deamination of AMP to inosine monophosphate (IMP), or adenosine to inosine. Eight intact extracorporally perfused pig hearts were rendered regionally ischemic by reducing the left anterior descending coronary artery blood flow by 60% for 40 minutes. Adjacent myocardium supplied by the circumflex artery was held aerobic throughout the study. Myocardial oxygen consumption and regional systolic shortening in the left anterior descending perfusion bed fell by 50 and 32%, respectively. Myocardial ammonia production increased significantly (p = 0.008) and tissue ammonia concentration was 55% greater in the ischemic left anterior descending bed than in the aerobic circumflex bed (p = 0.003). Compared to the circumflex bed, ATP and creatine phosphate concentrations in the left anterior descending bed were decreased by 41 and 53%, respectively. There were no significant increases in AMP or IMP levels, however there were dramatic increases of 525 and 397% in adenosine and inosine levels in the ischemic tissue. Thus, myocardial ammonia production was stimulated by ischemia without an increase in IMP levels. Combined with the fact that adenylate deaminase levels in the swine myocardium are normally low, this leads to the likely conclusion that source of the increased myocardial ammonia production during ischemia is deamination of adenosine, not IMP formation from AMP.

Adenine Nucleotides↗
PubMed1994

Lactulose or paromomycin do not affect ammonia generation in the isolated perfused rat small intestine.

It has been hypothesized that the beneficial effect on hepatic encephalopathy of lactulose or neomycin might be exerted by their effect on intermediary glutamine metabolism and ammonia generation within enterocytes. We examined glutamine consumption and the production of alanine and ammonia (net substrate exchange in nmol min-1 g-1) in isolated vascularly and luminally perfused small intestine from rats with and without pretreatment with lactulose (2.0 g/kg) or paromomycin (60 mg/kg). Without pretreatment, 50 mM lactulose or 1 mM paromomycin were equally ineffective to significantly reduce the consumption of arterial glutamine (-92 +/- 5 vs. -80 +/- 6 vs. -71 +/- 6 for controls, lactulose, or paromomycin; mean +/- SEM, n = 6 each, n.s. by analysis of variance), and the production of alanine (41 +/- 3 vs. 44 +/- 3 vs. 61 +/- 7, n.s.) or ammonia (42 +/- 6 vs. 42 +/- 6 vs. 38 +/- 6, n.s.). Similarly, glutamine utilisation, and the release of alanine and ammonia were not different after pretreatment for 10 days. Also, both agents did not reduce glutamine absorption from the lumen (-170 +/- 9 vs. -171 +/- 6 vs. -219 +/- 25, n = 5 each) or the concomitant vascular release of metabolic products alanine (92 +/- 7 vs. 78 +/- 10 vs. 77 +/- 10 vs. 77 +/- 7, n.s.) and ammonia (73 +/- 6 vs. 69 +/- 7 vs. 65 +/- 8, n.s.). Our results do not support the hypothesis, that lactulose or paromomycin reduce ammonia generation by small intestinal mucosa through a specific effect on intermediary glutamine metabolism.

Amino Acids↗
PubMed1996

Carnitine and choline derivatives containing a trimethylamine group prevent ammonia toxicity in mice and glutamate toxicity in primary cultures of neurons.

Carnitine prevents acute ammonia toxicity in animals. We propose that acute ammonia toxicity is mediated by activation of N-methyl-D-aspartate receptors and have shown that carnitine prevents glutamate neurotoxicity. The aim of this work was to assess whether other compounds containing a trimethylamine group are able to prevent ammonia toxicity in mice and/or glutamate toxicity in primary neuronal cultures. It is shown that betaine, trimethylamine-N-oxide, choline, acetylcholine, carbachol and acetylcarnitine prevent ammonia toxicity in mice. They also prevent glutamate but not N-methyl-D-aspartate neurotoxicity. Choline, acetylcholine and acetylcarnitine afford partial (approximately 50%) protection at nanomolar concentrations and nearly complete protection at micromolar concentrations. Trimethylamine-N-oxide, carbachol and betaine afford nearly complete protection at approximately 0.2 mM. The protective effect against glutamate neurotoxicity is prevented by 2-amino-3-phosphonopropionic acid, an antagonist of metabotropic glutamate receptors. Atropine, an antagonist of muscarinic receptors, prevents the protective effect of most of the above compounds against ammonia toxicity in mice and against glutamate toxicity in cultured neurons. These results support the idea that acute ammonia toxicity is mediated by activation of N-methyl-D-aspartate receptors and that glutamate neurotoxicity could be prevented by activating metabotropic glutamate receptors and/or muscarinic receptors.

Ammonia↗
PubMed1997

[Evaluation of the effect of long term valproic acid treatment on plasma levels of carnitine, ammonia and amino acids related to the urea cycle in pediatric epileptic patients].

INTRODUCTION: Valproic acid (VPA) is an antiepileptic drug widely used in paediatrics. In spite of being a safe and effective anticonvulsant, VPA has been involved in the onset of changes in the metabolism of ammonia and carnitine, although few prospective studies have been made of this. OBJECTIVES: To evaluate the effect of long-term VPA administration, particularly on the metabolism of carnitine, ammonia and plasma amino-acids and the possible clinical repercussions of this in a group of epileptic patients studied prospectively and retrospectively. MATERIAL AND METHODS: A study was made of 102 epileptic children on long term anticonvulsant treatment mainly with VPA. These patients were divided into two groups: group I (n = 25) were studied prospectively (basal sample, after one, six and twelve months of treatment) and group II (n = 77) or long term treatment group (a single sample extraction). In each epileptic patient and in 56 children from a control group (group III) studies were made of free plasma carnitine, ammonia and amino-acids related to the urea cycle and the plasma levels of each anticonvulsant drug. RESULTS: It was observed that in group I there was a fall in plasma carnitine concentrations with time and a progressive rise which was statistically significant (p = 0.001) in plasma levels, mainly of ammonia, glutamine, glycine and ornithine, from the basal levels to those after a year of treatment in practically 100% of the children studied. In group II children on antiepileptic drugs, mainly VPA, were seen to have lower plasma carnitine levels than those in the control group and higher serum ammonia, glutamine and glycine levels than the healthy population not treated with anticonvulsants. These differences were statistically significant (p = 0.001). No relationship was found between the parameters studied and the plasma levels of the drug, type of epilepsy or presence of side effects. CONCLUSIONS: These changes show the negative effects of VPA on the metabolism of carnitine and ammonia. It would therefore seem advisable to monitor these parameters in epileptic children on long term antiepileptic treatment.

Adolescent↗
PubMed1998

Nitrogen-13-ammonia and oxygen-15-water estimates of absolute myocardial perfusion in left ventricular ischemic dysfunction.

UNLABELLED: Measurements of resting myocardial blood flow (MBF) in patients with chronic left ventricular ischemic dysfunction by 15O-water with 13N-ammonia and PET have yielded conflicting results. The aim of this study was to perform a head-to-head comparison of both tracers in the same patient population and to answer the question of whether distinctive tracer properties account for differences in estimates of MBF in chronically dysfunctional myocardium by both tracers. METHODS: A total of 30 patients with chronic dysfunction of the anterior myocardial wall due to significant left anterior descending coronary artery disease underwent PET measurements of absolute MBF in the anterior wall by use of 15O-water and 13N-ammonia before coronary revascularization by either coronary artery bypass graft (n = 24) or percutaneous transluminal coronary angioplasty (n = 6). Improvement of regional contractile function was assessed by two-dimensional echocardiography at a mean of 7.5 +/- 2.1 mo after revascularization. As judged from the changes in anterior myocardial wall motion after revascularization, patients were considered to have either reversibly (n = 16) or persistently (n = 14) dysfunctional myocardium. Estimates of MBF by 15O-water and 13N-ammonia, obtained in every patient before revascularization, were compared among the two patient groups by use of previously validated methods. RESULTS: With 13N-ammonia, resting regional MBF was significantly higher in reversibly as opposed to persistently dysfunctional segments [84 +/- 8 versus 48 +/- 6 ml (min x 100 g)(-1), mean +/- s.e.m., p < 0.01]. By contrast, no such difference was found when using 15O-water to measure MBF [74 +/- 6 versus 86 +/- 9 ml (min x 100 g)(-1), p = ns]. This was mainly due to the fact that the perfusable tissue fraction (PTF), a fitted parameter of the 15O-water model, was significantly higher in reversibly as opposed to persistently dysfunctional segments (0.63 +/- 0.03 versus 0.50 +/- 0.03, p < 0.05). As a consequence, the 15O-water perfusable tissue index (PTI), which is the ratio of the PTF to the anatomical tissue fraction, was greater in reversibly dysfunctional as opposed to persistently dysfunctional segments (1.07 +/- 0.07 versus 0.79 +/- 0.05, p < 0.01). CONCLUSION: This study demonstrates significant differences in MBF estimates between 15O-water and 13N-ammonia in chronically dysfunctional ischemic myocardium. Our results indicate that the 15O-water method yields higher absolute MBF values than the 13N-ammonia approach. Our results also support the use of PTI as a marker of myocardial tissue viability.

Adult↗
PubMed1998

Helicobacter pylori and plasma ammonia levels in cirrhotics: role of urease inhibition by acetohydroxamic acid.

BACKGROUND AND AIMS: The role of Helicobacter pylori as a cause of hyperammonaemia in cirrhotics has still not been fully clarified. This study was aimed at evaluating the effect of acute Helicobacter pylori urease inhibition by oral acetohydroxamic acid administration on blood ammonia levels in cirrhotic patients. METHODS: Twenty-nine cirrhotics (14 males, 15 females; mean age: 63 years; Child-Pugh class: 14 A, 9 B, and 6 C) undergoing upper gastrointestinal endoscopy were enrolled in the study. The presence of Helicobacter pylori infection was assessed by rapid urease test and histology. A semi-quantitative grading of bacterial density was also performed at histology. All patients received oral acetohydroxamic acid 750 mg, and blood samples for assessment of ammonia levels were taken before and at 15, 30, 60 and 90 minutes after administration. RESULTS: Helicobacter pylori infection was detected in 20 patients, while 9 patients were uninfected. Acetohydroxamic acid administration led to a significant reduction in blood ammonia levels at 15 and 30 minutes (mean +/- SD, 113 +/- 44 vs 101 +/- 43 and 93 +/- 38 micrograms/dl, respectively; p = 0.002) only in patients with Helicobacter pylori infection. Moreover, the reduction was statistically significant only in Child-Pugh B/C class patients and in those with moderate/marked Helicobacter pylori density in gastric mucosa. Basal ammonia levels did not differ between Helicobacter pylori positive and negative patients, nor in patients with mild and moderate/marked Helicobacter pylori density in gastric mucosa, while Child-Pugh class B/C cirrhotics had higher basal ammonia levels than class A cirrhotics, in both Helicobacter pylori positive and negative groups. CONCLUSIONS: Our data showed that Helicobacter pylori urease inhibition by acetohydroxamic acid administration significantly reduces blood ammonia levels in patients with more advanced liver cirrhosis and in those with a high bacterial density in gastric mucosa.

Aged↗
PubMed1976

Effect of fatty acids on the disposition of ammonia.

Subcoma doses of fatty acids and ammonium salts injected intraperitoneally at the same time into rats or cats act synergistically to produce coma. Under these circumstances, the blood ammonia, is more than double that when the NH4+ is given alone. After these observations a rat liver homogenate system was utilized to study the effect of fatty acids on ammonia utilization in urea, glutamate and glutamine synthesis in vitro. Acetylglutamate-catalyzed urea synthesis was completely inhibited by 45 mM octanoate and was depressed 46% by 9.5 mM octanoate. Citrulline synthesis was similarly inhibited 86 and 28%, respectively. The concentration of liver octanoate at the moment of occurrence of coma after an in vivo injection was approximately 10 mM. The inhibitory effect of fatty acids on the utilization of NH4+ in the urea cycle was greater the longer the fatty acid chain. The critical step in this interference with ammonia metabolism was the inhibition of carbamyl phosphate synthetase. Argininosuccinate synthetase activity was also inhibited to a lesser degree, but ornithine transcarbamylase, argininosuccinate lyase and arginase were unaffected. Glutamate dehydrogenase was likewise inhibited in liver (83%) and brain (43%) by 13 mM octanoate, whereas glutamine synthetase was unaffected. Thus, the two main processes whereby ammonia is metabolized were inhibited by fatty acids at concentrations that exist pathologically, which accounts, at least in part, for the rise in blood ammonia in vivo.

Ammonia↗
PubMed1999

Synthesis of Nanosize Silica in a Nonionic Water-in-Oil Microemulsion: Effects of the Water/Surfactant Molar Ratio and Ammonia Concentration.

The effect of ammonia concentration on the region of existence of single-phase water-in-oil microemulsions has been investigated for the system polyoxyethylene (5) nonylphenyl ether (NP-5)/cyclohexane/ammonium hydroxide. The presence of ammonia decreases the size of the microemulsion region. A minimum concentration of surfactant (estimated at about 1.1 wt%) is required for solubilization of the aqueous phase; this value is not significantly affected by ammonia concentration. As indicated by fluorescence spectral data, the transition between bound and free water occurs when the water-to-surfactant molar ratio is about 1 and the presence of ammonium hydroxide does not appear to have a significant effect on this. Ultrafine (30-70 nm diameter), monodisperse silica particles produced by hydrolysis of tetraethoxysilane (TEOS) in the microemulsion show a complex dependence of the particle size on the water-to-surfactant molar ratio (R) and on the concentration of ammonium hydroxide. At relatively low ammonia concentration in the aqueous pseudophase (1.6 wt% NH3) the particle size decreases monotonically with increase in R. However, for higher ammonia concentrations (6.3-29.6 wt% NH3) a minimum in particle size occurs as R is increased. These trends are rationalized in terms of (a) the effects of the concentration, structure, and dynamics of the NP-5 reverse micelles on the hydrolysis and condensation reactions of TEOS, and (b) the effects of ammonia concentration on the stability of the microemulsion phase, the hydrolysis/condensation reactions of TEOS, and the depolymerization of siloxane bonds. Copyright 1999 Academic Press.

Journal Article↗
PubMed1984

Prevention of ammonia toxicity by L-carnitine: metabolic changes in brain.

L-Carnitine when injected in mice 30 min before an LD100 of ammonium acetate (12 mmol/kg body weight, intraperitoneal) reduced mortality (100% survival with 16 mmol L-carnitine/kg) and prevented the appearance of symptoms of ammonia toxicity. Brain ammonia decreased in the animals given L-carnitine. Ammonia decreased the levels of glutamate in brain; they were partially restored by L-carnitine, which also reduced the increase in brain glutamine in animals given only ammonia. The redox state of the brain was altered following ammonia intoxication. The ratio of lactate to pyruvate in the cytosol increased while that of glutamate to alpha-ketoglutarate in the mitochondria decreased. These ratios were partially restored by L-carnitine. The implications of these findings are discussed relative to the mechanism of ammonia toxicity.

Acetates↗
PubMed1989

Ammonia-induced swelling of rat cerebral cortical slices: implications for the pathogenesis of brain edema in acute hepatic failure.

The pathogenesis of brain edema in fulminant hepatic failure is incompletely understood. Our previous studies in models of this disease suggest the presence of a cytotoxic mechanism; as cortical astrocytes appeared predominantly swollen, we hypothesized that ammonia, metabolized to glutamine solely within this cell, could play a role in brain water accumulation. We determined ammonia levels in different brain regions of rats after hepatic devascularization, a model previously shown to exhibit brain edema. Concentrations of 2.5 mM were observed in the edematous cerebral cortex. We then added several concentrations of ammonium chloride to the first cortical brain slice, a preparation used to study cytotoxic brain edema. At a final bath concentration of ammonia of 5 and 10 mM, swelling could be detected: a decrease in the space of distribution of inulin was seen at the 10 mM concentration, suggesting intracellular water accumulation. Neuropathologically, astrocytes appeared involved even at subswelling doses of ammonia. Octanoic acid, at a 10 mM concentration, also resulted in demonstrable swelling. Ammonia, at concentrations in the incubation bath that approach the levels seen in an in vivo model of brain edema, results in water accumulation of cortical brain slices. Toxins implicated in the pathogenesis of hepatic encephalopathy, such as ammonia and octanoic acid, may, result in brain water accumulation.

Ammonium Chloride↗