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Biomedical subjects

W Banner

Publications and source records attributed to W Banner.

At least 37 records · Page 2Linked to original sources
PubMed1990

Failure of CAVH to remove digoxin-Fab complex in piglets.

Digoxin toxicity may be associated with renal failure and an inability to excrete the digoxin-Fab (antibody fragment) complex used in detoxification. We are unaware of any previous reports regarding the removal of digoxin-Fab fragment complex by continuous arteriovenous hemofiltration. Continuous arteriovenous hemofiltration allows ultrafiltration of molecules less than 50,000 daltons. Because the digoxin-Fab fragment complex has a molecular weight of 45 - 50,000 daltons, we evaluated the efficiency of continuous arteriovenous hemofiltration in removing the digoxin-Fab fragment complex. Three piglets were given 100 mcg/kg digoxin IM, in divided doses. Animals were anesthetized and continuous arteriovenous hemofiltration was begun using a Diafilter 10 cartridge. A mean ultrafiltration rate of 3.6 +/- 0.4 ml/min was obtained. The system equilibrated for 30 minutes and initial serum and ultrafiltrate digoxin levels were obtained. Mean serum values were total 6.20 +/- 1.74 ng/ml and free 3.72 +/- 0.88 ng/ml. Digibind 40 mg IV was given and then samples of serum and ultrafiltrate were obtained at 30, 60 and 90 minutes for digoxin levels. Mean values were as follows: 30 min serum total 54.23 +/- 26.13 ng/ml and free 0.08 +/- 0.08 ng/ml; 60 min serum total 61.24 +/- 27.31 ng/ml and free 0.07 +/- 0.04 ng/ml; and 90 min serum total 67.63 +/- 26.78 ng/ml and free 0.10 +/- 0.10 ng/ml. Ultrafiltrate levels throughout the experiment were negligible (less than or equal to 0.04 ng/ml). Continuous arteriovenous hemofiltration appears to be ineffective in removing the digoxin-Fab fragment complex.

Animals↗
PubMed1989

Hemodynamic effects of experimental iron poisoning.

The hemodynamic effects of severe iron poisoning were studied in five mongrel dogs. Anesthetized animals were instrumented with arterial, venous, and pulmonary artery thermodilution catheters. Iron intoxication was induced by orogastric administration of ferrous sulfate (600 mg/kg elemental iron). Pulmonary artery wedge pressure values were maintained near preintoxication values by saline infusion, and sodium bicarbonate (1.5 mEq/kg/dose) was given for pH less than 7.25. Hourly hemodynamic measurements were obtained for five hours. Cardiac output, mean arterial pressure, pH, and heart rate decreased significantly (P less than .05), whereas systemic vascular resistance, left ventricular stroke work, and oxygen consumption did not change. All animals developed metabolic acidosis despite saline (3.6 +/- 0.9 L, mean +/- SD) and bicarbonate administration (4.2 +/- 0.8 mEq/kg). These findings suggest that decreased cardiac output was partially due to decreased heart rate but not to decreased preload or abnormal left ventricular afterload. Alkali therapy and maintenance of oxygen consumption did not prevent development of metabolic acidosis.

Acidosis↗
PubMed1989

Continuous arteriovenous hemofiltration in experimental iron intoxication.

This study evaluated continuous arteriovenous hemofiltration (CAVH) as a method for removing the iron-deferoxamine complex in experimental iron intoxication. Five anesthetized dogs were instrumented for hemodynamic monitoring and then given 600 mg/kg of elemental iron as ferrous sulfate. After a 3-h absorption period, CAVH was begun from the femoral artery to femoral vein. Deferoxamine was infused into the arterial lines of the CAVH cartridge at increasing doses. We found a dose-dependent increase in the ultrafiltrate excretion of iron. However, most of the deferoxamine was excreted unbound. The efficiency of complex formation was greater at lower BP and ultrafiltrate formation rate, suggesting that inadequate mixing of deferoxamine with blood may occur when arterial administration is used. Iron excretion in the urine over the same time period was not significantly greater than that removed by CAVH. We conclude that CAVH can remove iron using deferoxamine as a chelating agent.

Animals↗
PubMed1989

Nonlinear dopamine pharmacokinetics in pediatric patients.

Dopamine steady-state concentrations were determined in 15 pediatric patients from 3 days to eight years of age receiving continuous infusions of dopamine. The first-order kinetic model does not accurately describe the kinetics of dopamine in these patients based on the finding that clearance varied as a function of concentration. A saturable protein binding model is described and provides a more accurate description of the behavior of the data. Using multivariate analysis, changes in dopamine kinetics were found as a function of weight. Furthermore, the co-administration of dobutamine altered the kinetics of dopamine. These data support the use of free dopamine concentrations rather than total concentration for studies of dopamine pharmacokinetics. Evaluation of total clearance of dopamine is of limited value, and changes in protein binding and intrinsic clearance must be considered in future studies of this drug.

Child, Preschool↗
PubMed1987

Pulmonary vascular responses induced by the pyrrolizidine alkaloid, monocrotaline, in rats.

Studies were conducted with isolated segments of pulmonary artery to characterize vessel contractility in monocrotaline-induced pulmonary hypertension. Contractions of pulmonary artery segments from rats given monocrotaline in drinking water (20 mg/l) for up to 20 days were measured in tissue baths. Dose response curves were produced with norepinephrine or serotonin and the response to 120 mM potassium chloride (KCl) was measured. Monocrotaline treatment significantly reduced the KCl-induced maximum contractile responses of pulmonary artery. Norepinephrine-induced maximal contractions (both in terms of mg developed force and as percentage of KCl-induced contractions) decreased with increasing length of monocrotaline treatment. Serotonin-induced maximal contractions were not altered by monocrotaline treatment. A minimum of 4 days treatment with monocrotaline drinking water reduced the contractile responses of pulmonary artery removed 16 days later. In separate experiments using continuous exposure to monocrotaline, a minimum of 15 days treatment was required before contractile activity was significantly altered. Results indicate monocrotaline treatment reduces the contractile activity of muscular pulmonary artery. Alterations in vessel responsiveness were produced after a minimum of 4 days treatment with monocrotaline in drinking water (an estimated exposure of 14-20 mg/kg) but required 15-20 days to develop.

Animals↗
PubMed1987

The effects of esmolol on the hemodynamics of acute theophylline toxicity.

The effects of esmolol, a beta 1-selective adrenergic receptor antagonist with a short duration of action, were studied in a canine model of the hemodynamics of theophylline toxicity. Animals were anesthetized, then given 50 mg/kg aminophylline IV over 20 minutes followed by a continuous infusion of 1.75 mg/kg/hr. Hemodynamic parameters, including heart rate, cardiac output, systemic blood pressure, pulmonary arterial pressure, and pulmonary artery wedge pressure, were measured every 30 minutes along with plasma catecholamines and theophylline levels. Marked tachycardia was seen in the intoxicated state, with heart rate rising from a baseline of 128.0 +/- 8.3 beats per minute (BPM) to 179.0 +/- 7.4 BPM (P = .012). This was associated with increases in catecholamines (baseline norepinephrine .04 +/- .04 ng/mL plasma rose to .42 +/- .21 ng/mL plasma after intoxication, P = .048). The average serum theophylline level during the experiment was 44.0 +/- 1.1 micrograms/mL serum. Esmolol then was given by IV infusion in these animals in doses of 25, 50, and 100 micrograms/kg/min. It returned the heart rate to the preintoxication baseline in a dose-related manner. Esmolol did not decrease cardiac output or lower blood pressure.

Acute Disease↗
PubMed1986

Experimental chelation therapy in chromium, lead, and boron intoxication with N-acetylcysteine and other compounds.

The usefulness of N-acetylcysteine (NAC) as a chelating agent was studied for the toxin potassium dichromate, lead tetraacetate, and boric acid. Mature Sprague-Dawley rats were intoxicated with these substances and placed in metabolic cages. Urinary excretion rates of intoxicant and total urine volume were determined during treatment with N-acetylcysteine, calcium EDTA, and/or dimercaptosuccinic acid, N-acetylcysteine proved to be the most effective agent at increasing the excretion of chromium and boron and was also able to reverse the oliguria associated with these toxins. Dimercaptosuccinic acid was most effective at the chelation of lead. NAC did not increase the excretion of lead. We conclude that NAC may be useful in intoxications due to chromate and borate and is effective at reversing the oliguria associated with these intoxicants.

Acetylcysteine↗
PubMed1986

Why read a pharmacokinetic article?

Clinicians are being increasingly asked to make clinical judgments on the basis of serum drug concentrations. The interpretation of these measurements in the clinical setting can be aided by a basic understanding of pharmacokinetics. By relating the dose of a drug to a serum concentration under known conditions, pharmacokinetic values may be calculated to assess the validity of the measured serum concentration. To appreciate the normal range and factors that may influence these pharmacokinetic values, the pharmacokinetic article is a valuable resource. A second value to these references is the establishment of reliable methods to achieve desired concentrations on the basis of measured values. By learning some basic definitions, the reader will be better prepared to deal with the interpretation of clinically relevant data in the literature and in the clinical setting.

Humans↗
PubMed1986

Iron poisoning.

Iron poisoning continues to be a major toxicologic problem, with major impact on the gastrointestinal and circulatory systems. Failure to recognize the severity of iron intoxication may result in an inappropriate level of intervention. By using estimates of the total body burden of iron, clinical symptoms, and the serum iron concentration, an appropriate decision can be made to initiate aggressive chelation therapy with deferoxamine. In severe intoxication, the use of intravenous deferoxamine is indicated, along with supportive care, with particular attention to maintaining the intravascular volume. Other important measures include correction of acidosis and disorders of coagulation and replacement of blood components when there is evidence of gastrointestinal hemorrhage. Under rare circumstances in which large numbers of iron tablets are present in the gastrointestinal tract, surgical removal may be indicated. In addition, measures such as hemodialysis and exchange transfusion should be reserved for those unusual poisonings in which more conservative therapy is unsuccessful. In rare cases of iron intoxication, late sequelae such as hepatic necrosis and gastrointestinal scarring with obstruction may occur. The prompt recognition and initiation of management of children with acute iron poisoning is the single most critical element in decreasing the morbidity and mortality associated with these products.

Absorption↗
PubMed1986

Characterization of muscarinic receptors of the rabbit ear artery smooth muscle and endothelium.

Muscarinic receptors of the rabbit ear artery were characterized by observing the effect of the subtype selective antagonist pirenzepine on functional responses and radioligand binding. Pirenzepine has been shown to bind with high affinity to muscarinic receptors of certain brain regions and peripheral ganglia (M1 subtype) and with low affinity to receptors of the heart and upper gastrointestinal tract (M2 subtype). The affinity (pKB) of pirenzepine for the muscarinic sites of the endothelium was determined by the competitive antagonism of the relaxation response to methacholine. Schild analysis gave a pKB of 6.5 (320 nM) which is consistent with the low affinity, M2, subtype of muscarinic receptor. Removal of the endothelium eliminates any response to muscarinic agonists but does not decrease the density of muscarinic binding sites determined by binding of the specific ligand (-)-[3H]quinuclidinyl benzilate. This indicates a second group of muscarinic receptors most probably located on vascular smooth muscle cells for which there is no known function. The pKi for pirenzepine at these sites, as determined by the inhibition of (-)-[3H]quinuclidinyl benzilate binding, was 6.26 (550 nM) which is also consistent with a low affinity subtype. Thus, both types of vascular muscarinic binding sites, those on the endothelium which mediate relaxation and those on the vascular smooth muscle cells, are of the low affinity, M2, subtype.

Acetylcholine↗
PubMed1984

Lack of specific (3H) prazosin binding sites in dog and rabbit cerebral arteries.

In order to explore the characteristics of alpha adrenergic receptors on cerebrovascular smooth muscle, specific binding sites for the alpha 1 adrenergic ligand, (3H) prazosin, were studied in blood vessel homogenates. No specific (3H) prazosin binding was found in either rabbit or dog cerebral arteries, but specific binding was demonstrated in the rabbit saphenous and ear arteries. In the ear artery 3H-prazosin binding was saturable with a Kd of 0.51 +/- 0.20 nM and a Bmax of 89 +/- 29 fmoles/mg protein. To confirm the adequacy of our membrane preparation, homogenates of both dog and rabbit cerebral arteries showed saturable specific binding with two different ligands: one for muscarinic receptors, [3H](-) quinuclidinyl benzilate (QNB) and one for alpha 2 adrenergic receptors, (3H) yohimbine. The results of these studies demonstrate a lack of alpha 1 adrenergic receptors on cerebral blood vessels, confirming functional studies showing only a weak contractile response to norepinephrine.

Animals↗
PubMed1984

Treatments for Centruroides exilicauda envenomation.

We treated two cases of severe envenomation by the scorpion Centruroides exilicauda. The first infant was treated with a species-specific scorpion antivenom, which produced a delayed but dramatic return of all vital signs to normal. A second infant was treated with two doses of intravenous propranolol hydrochloride and had a rapid, dramatic decrease in heart rate but only gradual resolution of neurologic symptoms. These cases demonstrate the severe symptoms of envenomation by this scorpion in the infant and show two possible treatments.

Antivenins↗