Search PubMed⌕ Search

Biomedical subjects

A T Blei

Publications and source records attributed to A T Blei.

At least 73 records · Page 4Linked to original sources
PubMed1991

Intracellular pH rises and astrocytes swell after portacaval anastomosis in rats.

The basis for astrocytic swelling after the early period after portacaval anastomosis (PCA) is poorly defined. In other eukaryotic cells intracellular pH (pHi) and volume are determined, in part, by the same general mechanisms, yet how astrocytic pHi varies with enlargement of these cells after PCA is unknown. Therefore, direct measurements of pHi in astrocytes were made and compared with pericapillary astrocytic area as determined from electron micrographs in rats 5-8 days after PCA. Astrocytic area (n = 14 measurements for each group) was found to be significantly (P less than 0.0009) greater in PCA animals (n = 3) than in sham-operated control animals. (n = 3). Double-barrel pH-sensitive microelectrodes were used to measure pHi in neocortical cells defined by electrophysiological criteria to be astrocytic. Astrocytes (n = 25) from PCA animals (n = 5) had a resting membrane potential of 72 +/- 5 mV (mean +/- SD) and an pHi of 7.11 +/- 0.11 while comparable cells (n = 12) from sham-operated controls (n = 2) had a membrane potential of 81 +/- 6 mV and an pHi of 7.00 +/- 0.10. Astrocytes from PCA animals were significantly more depolarized (P less than 0.001) and alkaline (P less than 0.009), at a time when they were also significantly larger than those from sham-operated controls. Astrocytes are known to become more alkaline when they are activated by brief depolarizing stimuli. However, this is the first demonstration that such an interrelationship can also exist for steady-state conditions of these cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Endotoxin and the hyperdynamic circulation of portal vein-ligated rats.

Humoral factors may be responsible for the hyperdynamic circulation seen in portal hypertension. Endotoxin, a peripheral arteriolar vasodilator, has been proposed to mediate this hemodynamic picture. We examined the pathogenic role of endotoxin in portal vein-ligated rats, a prehepatic portal hypertensive model with a well-developed hyperdynamic circulation. To this end, we (a) administered oral neomycin, a poorly absorbable antibiotic, at doses of 50 and 100 mg/day for 7 days and found no evident splanchnic hemodynamic effects of a 2-log-fold reduction of cecal aerobic bacterial flora as assessed by the radioactive microsphere technique in portal vein-ligated rats studied in the postanesthesia awake state; (b) assayed endotoxin in arterial samples using a quantitative limulus assay and found no evidence of endotoxinemia in PVL rats; (c) induced a state of endotoxin tolerance by repeated daily intraperitoneal injections of low-dose endotoxin and found no amelioration of the hyperdynamic state in portal vein-ligated rats. Our results do not support the hypothesis that endotoxin plays a major pathogenic role in the hyperdynamic circulation of this experimental model.

Ammonia↗
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↗
PubMed1989

Effect of body temperature on brain edema and encephalopathy in the rat after hepatic devascularization.

Brain edema is a fatal complication of fulminant hepatic failure and its pathogenesis remains unclear. To determine its presence in a model of ischemic hepatic failure, rats were subjected to a portacaval anastomosis followed by hepatic artery ligation. Brain water was measured using the sensitive gravimetric method. Preliminary studies revealed marked hypothermia in devascularized animals kept at room temperature (26.9 degrees +/- 2.8 degrees C). An additional group of devascularized rats was kept in an incubator. As expected for hypothermia, such animals had a lower arterial pressure and heart rate; the duration of encephalopathy was markedly prolonged. Water content of the cortical gray matter was only increased in normothermic devascularized rats: 80.14% +/- 0.31%, normal; 80.06% +/- 0.22%, portacaval shunt only; 80.42% +/- 0.26%, devascularized at room temperature; 81.29% +/- 0.38%, devascularized at controlled temperature (p less than 0.001). Such differences could not be detected using the dry-weight technique in whole cerebral hemispheres. Astrocyte changes in the cortical gray matter were noted in both edematous and nonedematous devascularized groups, coupled with the presence of vesicles containing horseradish peroxidase in the endothelial capillary cell. This suggests that in this model, brain edema may be due to both a cytotoxic mechanism and changes in the permeability of the blood-brain barrier. Future studies with this widely used model will require strict control of temperature to allow interpretation of experimental results. A therapeutic role for hypothermia in the management of brain edema deserves further attention.

Animals↗
PubMed1988

Thrombosis of the splanchnic veins: CT diagnosis.

Fourteen patients had mesenteric, portal, or splenic venous thrombosis that was diagnosed primarily by contrast-enhanced CT. The group included five patients with coagulopathy, three with pancreatic carcinoma, two with cirrhosis and portal hypertension, one with pancreatitis, and one with hepatocellular carcinoma. In two patients, no etiology was determined. In all cases, CT easily identified low-density venous thrombosis, which frequently involved more than one vein. In four patients, all three splanchnic veins were involved; five patients had occlusion of two veins. In five patients, only one vein was involved. Additional CT findings included ascites, collateral veins, hepatomegaly, and splenomegaly. No venous wall enhancement was found. CT also was helpful in defining the cause of thrombosis in six of 14 patients. Mesenteric edema and/or bowel wall thickening was not identified. None of the patients had classic clinical evidence of splanchnic venous occlusion, and none died primarily of that disease. The major morbidity suffered by these patients stemmed from complications of splanchnic venous occlusion, and nine patients ultimately required sclerotherapy, splenectomy, and portal decompression. We conclude that CT is useful in the diagnosis of splanchnic venous thrombosis. Our experience suggests that mesenteric, splenic, and/or portal venous thrombosis may occur more commonly than has been previously thought and that the disease in many cases is not life threatening.

Adult↗
PubMed1988

Local effect of neurotensin on canine ileal blood flow, and its release by luminal lipid.

This study was performed to determine whether the level of neurotensin in mesenteric venous blood after lipid perfusion is sufficient to establish neurotensin as a mediator of lipid-induced mesenteric vasodilation. In anesthetized dogs, arterial flow to segments of the ileum was recorded, and blood was collected for measurement of neurotensin-like immunoreactivity, and neurotensin and metabolites. Perfusion of the lumen with micellar lipid resulted in an increase in blood blow from 37.7 +/- 4.1 to 44.5 +/- 3.9 ml/min/100 g (p less than 0.01; n = 8); flow to a control segment did not change. Venous plasma neurotensin-like immunoreactivity doubled, and neurotensin also increased (to 11.3 +/- 3.9 fmol/ml; p less than 0.05). Close intra-arterial infusion of neurotensin at 5 pmol/min increased blood flow to 44.3 +/- 3.4 ml/min/100 g (p less than 0.025; n = 5); flow to a control segment did not change. Neurotensin-like immunoreactivity increased to the same extent as with lipid perfusion, and neurotensin increased to 28.6 +/- 6.1 fmol/ml (p less than 0.05). No accumulation of metabolites was detected in either experiment. Thus, infused neurotensin caused increased ileal blood flow at a level in venous plasma comparable to that present after lipid perfusion, suggesting that neurotensin may have a role in the local regulation of ileal blood flow.

Animals↗
PubMed1988

Hemodynamic and renal effects of atrial natriuretic factor in portal hypertensive rats. Potentiation by Phe-Ile-Orn-vasopressin.

The effects of atrial natriuretic factor (ANF) on splanchnic hemodynamics and renal function in portal hypertensive models are described incompletely. Furthermore, ANF-induced vasodilatation and hypotension may limit the assessment of its own renal physiological effects. We infused ANF (human ANF 102-126) to anesthetized portal vein-ligated rats, a model with prehepatic portal hypertension. Arterial pressure was reduced by 17%, but portal pressure was unaffected. Diuresis and natriuresis were explained in part by an increase in glomerular filtration rate; in addition, renal vascular resistance was significantly decreased. The natriuretic response to ANF was slightly, but significantly, decreased in portal hypertensive rats as compared to controls (fractional excretion of sodium, 1.8 +/- 0.4 vs. 2.9 +/- 0.3; P less than .05). The addition of Phe-Ile-Orn-vasopressin, a V1 receptor agonist, normalized arterial pressure but induced a significant decrease in portal pressure (15 +/- 0.9 mm Hg base line vs. 12.8 +/- 0.7 combination group; P less than .01). Furthermore, the combination of both drugs markedly potentiated the natriuretic effects (0.4 +/- 0.1 microEq/min of control vs. 10.0 +/- 2.3 ANF vs. 32.2 +/- 3.3 combination group; P less than .001). The natriuretic potentiation resulted from increments in glomerular filtration rate and renal blood flow. Normalization of arterial pressure may enhance the renal physiological effects of ANF, in this portal hypertensive model.

Animals↗
PubMed1987

Protein C deficiency in splanchnic venous thrombosis.

Deficiencies of protein C activity and antigen were observed in eight consecutive patients with splanchnic venous thrombosis. There was a significant reduction in the ratio of protein C to factor X. Six of the eight patients had a decrease in antithrombin III, but free protein S antigen was within normal limits in all but two subjects. It is proposed that a thrombogenic stimulus such as stasis, altered hormonal milieu, or failure of hepatic clearance of activated coagulants results in consumption of protein C and antithrombin III, predisposing to splanchnic venous occlusion. This further impairs hepatic function, prevents restitution of protein C and antithrombin levels, and promotes continuing venous thrombosis. Thus, a vicious cycle of thrombosis and hepatic damage is perpetuated.

Adult↗
PubMed1987

Hemodynamic evaluation of isosorbide dinitrate in alcoholic cirrhosis. Pharmacokinetic-hemodynamic interactions.

Isosorbide dinitrate, a long-acting organic nitrate, has been shown to decrease portal pressure in the experimental animal and humans. We conducted a double-blind randomized hemodynamic evaluation of the effects of placebo and 10 mg and 20 mg isosorbide dinitrate in stable individuals with alcoholic cirrhosis. Baseline values for all three groups were similar. Isosorbide dinitrate resulted in a peak reduction of the hepatic venous gradient of 24.7% +/- 3.0%, with significantly decreased values 4 h after the administration of the 20-mg dose. A reduction of arterial pressure and cardiac index (peak decrease of 25.7% +/- 1.5%) was well tolerated by 13 of 15 patients. Changes in mean arterial pressure were not predictive of modifications in the hepatic vein wedge pressure. There was no relation between the area under the plasma isosorbide dinitrate concentration curve and hemodynamic changes. Levels of isosorbide-5-mononitrate, a vasoactive metabolite, were detectable for an 8-h period. Isosorbide dinitrate significantly reduced portal pressure in stable cirrhotics, in association with systemic hemodynamic changes. Thus, titration of isosorbide dinitrate is required to maximize hemodynamic benefits in individual patients. As the decrease in portal pressure is more predictable than the effect of previously tested pharmacologic agents, isosorbide dinitrate should be evaluated for its efficacy in the management of portal hypertension.

Blood Pressure↗
PubMed1986

Clinical significance of concurrent hepatitis B surface antigen and antibody positivity.

Over a period of 30 months, 64 patients with concurrently positive hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) were identified at two institutions. When all assays were considered, 23.9% of HBsAg-positive individuals exhibited anti-HBs. Both persistent HBsAg/anti-HBs positivity and variable changes in antigen or antibody status were observed among the 36 patients with follow-up beyond six months. When compared to a control group, these patients did not exhibit differences in risk factors for acquiring hepatitis B or in clinical and histological diagnoses. Concurrent HBsAg and anti-HBs was present at detection in 25 patients, while antibody appeared in the remaining 11 subjects. Subsequently, it was undetectable in seven of these 36 patients; no clinical changes occurred at the time of acquisition or loss of the antibody. The titer of the antibody was below 10 mIU/ml in 75% of these individuals. In 10 patients, the subtype of HBsAg was ad, while the anti-HBs was anti-y. Concurrent HBsAg and anti-HBs is a pattern frequently observed throughout the spectrum of hepatitis B-related events. The heterotypic antibody in these patients is of a low titer, and its appearance or disappearance is not associated with changes in the clinical course; simultaneous HBsAg/anti-HBs positivity does not appear to reflect a distinct clinical entity.

Adolescent↗
PubMed1986

Primary sclerosing cholangitis in the presence of a lupus anticoagulant.

Lupus anticoagulant, an immunoglobulin that prolongs the partial thromboplastin time, has been associated with thrombotic events, including deep venous thrombosis, pulmonary emboli, and Budd-Chiari syndrome. In this report, primary sclerosing cholangitis was diagnosed in a man with a 10-year history of multiple thrombotic events related to a circulating lupus anticoagulant. Progressive jaundice and pruritus developed, and sclerosing cholangitis was confirmed by direct cholangiography. Sclerosing cholangitis is the second hepatobiliary disease reported in association with a lupus anticoagulant.

Adult↗
PubMed1986

Brain edema in rabbits with galactosamine-induced fulminant hepatitis. Regional differences and effects on intracranial pressure.

Brain edema and intracranial hypertension are major complications of fulminant hepatic failure. We investigated the development of brain edema and monitored intracranial pressure in rabbits with toxic hepatitis induced by galactosamine. Using a gravimetric technique to assay small tissue samples, we found that brain water was increased in cortical grey matter, but not in subcortical, mesencephalic, and pontine white matter, or in the cerebellum. The proportion of water in cerebral grey matter in control animals was 80.96% +/- 0.49% with significant elevations to 81.96% +/- 0.47% and 82.95% +/- 1.49% in mild and severe encephalopathy, respectively. This corresponds to mean increases in tissue volume of 5.5% and 11.7%. The hippocampal grey matter also accumulated water in severe encephalopathy with a 30% increase in mean tissue volume. The regional increase in brain water was confirmed by the wet-dry weight method. Neither hypotension, hypoxia, nor severe hypoglycemia were present to account for the edema. Intracranial pressure was monitored continuously in unanesthetized rabbits via an intraventricular cannula as encephalopathy developed. The pressure was normal in the mild stage, but was intermittently elevated in animals with severe encephalopathy. The normal range of intracranial pressure was 2-9 mmHg and the range of peak values in galactosamine-treated rabbits was 18-55 mmHg. The regional differences in brain water accumulation suggest that cellular swelling and abnormalities in the movement of water across the blood-brain barrier may account for the brain edema in this model.

Animals↗
PubMed1984

Role of the liver in the disposition of intravenous nitroglycerin in the rat.

Previous studies have indicated that the liver is the main site of nitroglycerin (NTG) elimination when the drug is systematically infused. To examine this hypothesis, we measured the apparent systemic clearance (Cls) of nitroglycerin in anesthesized rats receiving a constant intravenous infusion at a dose of 100 micrograms per kg per min. Animals were divided into shunt and sham groups; the former had undergone a portal vein ligation 10 days prior to the study, while the latter was subjected to a sham operation. On the study day, half of the animals of each group also received probenecid at 200 mg/kg, i.v., a drug previously reported to inhibit organic nitrate ester reductase (ONER) activity in rat liver. Arterial NTG samples were obtained at 41, 43 and 45 min of infusion in all four experimental groups; Cls was 439 +/- 32 ml per kg per min (mean +/- S.E.) in sham, 460 +/- 44 in sham and probenecid, 477 +/- 39 in shunt, and 461 +/- 34 in shunt and probenecid animals. During NTG infusion, hepatic blood flow (measured with a constant infusion of indocyanine green) was decreased markedly in shunted rats as was liver/body weight, indicating hepatic atrophy. The specific activity of hepatic ONER was similar in all four groups. In spite of marked differences in hepatic blood flow and hepatic mass, the Cls was similar in all four groups. The liver does not appear to be a major site for the elimination of systemic nitroglycerin as hitherto assumed.

Animals↗