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Biomedical subjects

P Altmayer

Publications and source records attributed to P Altmayer.

At least 19 recordsLinked to original sources

[Effect of the volatile anesthetics halothane, enflurane and isoflurane on liver circulation in the human].

In 40 patients with normal liver function total hepatic blood flow (HBF) was determined by the indocyanine-green clearance method simultaneously with haemodynamic parameters, including cardiac output by means of the noninvasive thoracic electrical bioimpedance method. Furthermore, the influence of halothane, enflurane or isoflurane on HBF and the interaction with haemodynamic parameters was studied. HBF and the cardiocirculatory parameters were determined under normal conditions (waking state) and the 40 patients were then divided into 4 groups (each n = 10). After standardised induction of anaesthesia (0.3 mg/kg etomidate and 2 micrograms/kg fentanyl) and tracheal intubation (1.5 mg/kg suxamethonium chloride) an inhalation anaesthesia in O2/air under control of normal end tidal carbon dioxide concentration was performed by intermittent positive pressure ventilation. Anaesthesia was maintained in the 4 groups either with 1 MAC halothane, 1 MAC enflurane, 1 MAC isoflurane or 1.3 MAC isoflurane. The measurements were repeated at a steady of the desired end expiratory concentration of the respective volatile anaesthetic. All three anaesthetics produced a significant and comparable decrease of cardiac output and arterial blood pressure. Differences between halothane, enflurane and isoflurane in respect of haemodynamic parameters were only minimal. Contrariwise, marked differences could be seen in the effects of the anaesthetics on HBF. In the presence of halothane and enflurane HBF dropped to 58% and 56% resp. of the control value, whereas during isoflurane anaesthesia HBF remained unchanged. Furthermore, only during halothane anaesthesia a significant correlation between arterial blood pressure and HBF could be observed indicating a loss of autoregulation of the hepatic blood flow.

Adolescent

Interactions between thiopental and volatile anesthetics (halothane and isoflurane) in isolated heart preparations of the rat.

Thiopental uptake into heart muscle tissue was studied in spontaneously beating rat hearts (Langendorff preparation, 0.13-0.27 mmol/l thiopental in the perfusion fluid). Up to 0.19 mmol/l the concentration of thiopental in heart muscle tissue was increased vs. control when halothane (0.8 vol%) was present. Using a constant thiopental concentration (0.13 mmol/l) and 0.8, 1.5 or 2.0 vol% halothane +12%, +29% or +43% more thiopental was taken up into heart muscle tissue compared to the control. This increased uptake was not seen in the presence of 1.2 and 2.0 vol% isoflurane. Frequency of right rat atria was decreased by increasing thiopental concentrations (0.02-0.23 mmol/l in the incubation medium). Halothane (0.8 and 1.5 vol%) and isoflurane (1.0 and 2.0 vol%) alone had no influence on frequency of right atria. Both volatile anesthetics additionally increased the negative chronotropic action of thiopental when the corresponding higher concentration was applied. Contractile force of left rat atria was decreased concentration-dependently by thiopental (0.02-0.23 mmol/l). Halothane and isoflurane alone decreased contractility. Dependent on the concentration used, both volatile anesthetics further increased the negative inotropic action of thiopental, yet preferentially at higher barbiturate concentrations.

Animals

Increase of thiopental concentration in tissues of the rat due to an anesthesia with halothane.

In rats anesthetized with halothane (CAS 151-67-7) (1.5 vol%) and rats without any further treatment (control) the early distribution phase of thiopental (CAS 76-75-5) (i.v. 30 mg/kg) was studied. In serum and 8 tissues thiopental concentration (T) was determined using ultraviolet detection at 305 nm after extraction and TLC. In rats anesthetized with halothane, T in serum was significantly higher during the 30 min following the thiopental injection (at least +27% and maximally +51%) as compared to the control (same dose), and several pharmacokinetic parameters (e.g. central volume of distribution) were found to be changed thereby; furthermore, at 3, 10 and 30 min T was significantly increased in liver, brain, heart, lung and spleen; in kidney and skeletal muscle a rise of T was also seen, however, it occurred later (after 10 and 30 min). T in fat tissue increased time-dependently; a T-difference in adipose tissue between both groups was not observed. Thiopental was "trapped" during the early distribution phase to a considerable extent in the vessel-rich tissues of rats simultaneously anesthetized with halothane; this pharmacokinetic interaction might be explained hemodynamically: in many tissues regional blood flow is reduced by halothane; thereby a delayed "washout" of thiopental from the vessel-rich tissues could take place and redistribution would be delayed; additional factors as e.g. an increased binding of thiopental at tissue proteins could also play a role. An unusually high T was found at least temporarily in myocardial tissue due to this interaction between the two anesthetics.

Anesthesia

Increase of thiopental concentration in rat tissues due to anesthesia with isoflurane.

Thiopental distribution was studied in rats (30 mg/kg i.v.) anesthetized simultaneously with 1.25 "rat"-MAC isoflurane. The thiopental concentration in serum and several tissues was determined UV-photometrically at 305 nm after extraction and TLC. In the serum of rats anesthetized with isoflurane the thiopental concentration was significantly increased to +39----+74% in comparison to controls during 30 min following the barbiturate injection. Also in liver, brain, heart, kidney, lung and spleen of rats anesthetized with isoflurane the thiopental concentration was significantly increased at 3 and 10 min; at 30 min the difference vs. control had vanished in brain, heart, lung and spleen. Obviously, thiopental was transiently "trapped" during the early distribution phase to a considerable amount in these vessel-rich tissues when anesthesia with isoflurane was simultaneously performed; this pharmacokinetic interaction might be explained at least to some extent hemodynamically; in many tissues regional blood flow is reduced during anesthesia with isoflurane; thereby the "washout" of thiopental from the tissues and the redistribution are delayed.

Anesthesia, Inhalation

Cardiac output and liver blood flow in humans: effect of the volatile anesthetic halothane.

In 40 men with normal circulatory and liver function, from whom 10 were undergoing general anesthesia with halothane for minor orthopedic surgery, the relationship between hemodynamic parameters and total hepatic blood flow (HBF) was investigated. Cardiac output (CO) was measured noninvasively by means of the thoracic electrical bioimpedance method, systemic arterial blood pressure (BPsys, BPdia, mean arterial pressure) by an automated oscillometric device and HBF by indocyanine green clearance. In the subjects without halothane anesthesia no relationship was found between BP and HBF, but a significant correlation could be seen between CO and HBF, whereby the fraction of HBF decreased with increasing CO. In contrast, in the presence of halothane the systemic arterial blood pressure correlated with the HBF, indicating a loss of autoregulation of the liver circulation.

Adult

Increased binding of thiopental in tissue homogenates of the rat in the presence of a volatile anesthetic.

Thiopental (CAS 76-75-5) binding (0.4 mmol.l-1) in tissue homogenate of rats (liver, brain, heart, kidney, lung, spleen and skeletal muscle) was studied by equilibrium dialysis. Percentage of thiopental bound was relatively low in homogenate of brain, lung, spleen and skeletal muscle (14-19%); it was much higher in that of liver, heart and kidney (24-27%). Simultaneously present halothane (11.8 mmol.l-1) increased the percentage of thiopental bound in the homogenate of all tissues investigated at least to a factor of 1.4 (spleen) and maximally of 2.4 (brain). The same phenomenon of an increased thiopental binding in tissue homogenate was found in the presence of 10.3 mmol.l-1 enflurane (except skeletal muscle) and 10.2 mmol.l-1 isoflurane (except kidney, spleen and skeletal muscle), yet to a significantly lower extent in the presence of these halogenated ethers as compared with halothane.

Anesthetics

[Oral premedication with midazolam in children].

One hundred children aged between 6 months and 10 years undergoing elective urological surgery, received 0.4 mg/kg midazolam orally about 20 minutes prior to the arrival in the operation theatre. The physiological state of the children was estimated and recorded pre- and postoperatively at defined, comparable and representative circumstances by a specially developed design. In the preoperative period orally administered midazolam had only a mild or non sedative effect in 76-84% of the children, 67-88% of the small patients behaved cooperatively or passively and 70-84% showed an indifferent or euphoric state of mind. Postoperatively 57-89% of the children were markedly sedated; therefore, the estimation of behaviour and state of mind was of minor significance. The circulatory parameters were altered only minimally. Systolic blood pressure and heart rate changed slightly but significantly compared to the preoperative values the day before surgery: a preoperative increase to a maximum immediately after the insertion of the venous cannula and a postoperative maximum after recovery. Side effects were rare (hiccough 5%, vomitus 4%, laryngospasm 1%, stridor 1%). Our results suggest that oral premedication with midazolam in children can be recommended to avoid traumatic or unpleasant alterations resulting from intramuscular injections or rectal applications. Therefore, we prefer this kind of premedication in paediatric patients.

Administration, Oral

Determination of cardiac output during positive end-expiratory pressure--noninvasive electrical bioimpedance compared with standard thermodilution.

Many investigators have demonstrated the accuracy and reliability of thoracic electrical bioimpedance (TEB) in spontaneously breathing patients and under mechanical intermittent positive-pressure ventilation. Most of these studies showed a good correlation between TEB and invasive methods, such as thermodilution (TD) or the Fick method. But during PEEP, contrary results occur when comparing TEB and TD. In six patients undergoing neurosurgical interventions, TEB cardiac output measurements were compared during zero end-expiratory pressure (ZEEP) and during PEEP at 8 cm H2O with a low respiratory rate. The data revealed a good correlation during ZEEP (r = .93) and during PEEP (r = .91). There was no significant statistical difference when measuring cardiac output by TEB during ventilation with PEEP. During normal or decreased cardiac output, TEB overestimated cardiac output compared with TD, whereas TEB underestimated cardiac output compared with TD during increased cardiac output, especially during PEEP.

Brain Neoplasms

Thiopental binding to human serum albumin in the presence of halothane.

In vitro thiopental binding (substrate concentration 0.04.10(-3) M = 10 micrograms/ml) to 1% human serum albumin (HSA) increased significantly from 40.2% (= control) to 47.3% in the presence of 1.18.10(-3) M = 2.84 vol% halothane. A 4-fold higher halothane concentration (4.71.10(-3) M) had an even greater effect with an increase in the thiopental fraction bound to 55.5%. With a constant HSA concentration (1% or 5%) and thiopental concentrations in the range 0.01-1.5.10(-3) M or 0.01-0.38.10(-3) M, respectively, the halothane effect (increase in thiopental binding) was always evident, as well as in other experiments with constant thiopental concentration (0.04.10(-3) M) and variation in the HSA concentration (0.5-10%). Two classes of binding sites for thiopental were apparent at the HSA molecule. In the control experiments the following binding parameters were found: n1 = 0.01, k1 = 181.10(3) M-1; n2 = 45.73, k2 = 0.08.10(3) M-1, K = 5.47.10(3) M-1. In the presence of halothane the binding parameters changed as follows: n1 = 0.14, k1 = 29.4.10(3) M-1; n2 = 11.68, k2 = 0.42.10(3) M-1, K = 9.02.10(3) M-1.

Binding Sites

pH-dependent interaction of halothane upon thiopental binding to human serum albumin.

At pH 7.4 the binding of thiopental to human serum albumin (HSA) was increased in the presence of halothane. In order to obtain information about the mechanism of this interaction, in vitro binding experiments by means of equilibrium dialysis were carried out at different pH values. At pH 4.97 the binding of thiopental to HSA 1% was low (23% bound) and not influenced by halothane. An increase of thiopental binding caused by halothane could be seen at pH 7.4 (55% bound vs. 41% in the control = without halothane) and at pH 8.23 (62% vs. 54%). At pH 10.15 an opposite interaction was found: in the presence of halothane thiopental binding was considerably decreased (36.2% vs. 47.0% in the control). Evaluation of the binding parameters of experiments using increasing substrate concentrations (Scatchard plot) revealed quite different changes of the two classes of binding sites of HSA for thiopental. It is assumed that halothane causes reversible conformational changes of the albumin molecule resulting in altered binding characteristics for thiopental.

Binding Sites

[A computer-assisted noninvasive monitoring system with graphic display of online determination of cardiovascular parameters].

During anesthesia the cardiovascular system is usually assessed on the basis of heart rate and arterial pressure, although the most important hemodynamic measurement is that of flow. A method for the non-invasive measurement of cardiac output is based on thoracic electrical bio-impedance. The NCCOM3-R7 is a non-invasive cardiac output monitor that makes use of thoracic electrical bioimpedance, which has been shown to provide results comparable with thermodilution in various hemodynamic states both in animals and humans. A new on-line hemodynamic monitoring system has been developed using the non-invasive NCCOM3-R7 (BoMed) cardiac output monitor, a portable microcomputer (NEC Multispeed) in connection with a software package CDDP-1 (BoMed), a Dinamap automatic arterial pressure monitor (Critikon) and an additional 14" display. Every 16 heart beats the cardiac output monitor transfers 11 cardiodynamic parameters in ASCII-format to the microcomputer, where the data are stored. Using the CDDP-1 program the current cardiodynamic status of the patient is displayed numerically and graphically on the monitor screen. Mean arterial pressure is determined by Dinamap and the data must be entered manually in the menu. The program then calculates systemic vascular resistance and left ventricular work index, the CVP being set to 3 torr and PAOP to 6 torr. In the graphic display the current hemodynamic status is shown and the underlying situation is analyzed in terms of systemic vascular resistance and volume-dependent contractility. The reliability of this on-line monitoring system is demonstrated in a high-risk patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General

[Postoperative monitoring following short duration surgery of the ear, nose and throat. Experiences with midazolam as an anesthesia induction agent].

A combination of midazolam and alfentanil was used on 24 patients for induction of general anaesthesia. Anaesthesia was maintained with N2O/O2 and repeated injections of alfentanil. The mean operation time was 40.8 min. At the end of surgery the patients recovered 4.8 min after antagonisation of the alfentanil with naloxon, and the endotracheal tube could be removed. Thirty, 60 and 120 min after extubation the patients were asked to perform a Marschner's test, which measures the ability to concentrate on fast intellectual work. Up to 660 simple arithmetical additions could be checked within 7.5 min. The intellectual performance recovered quickly: after 30 min 79% of the pre-operative values were reached, after 60 min 85% and after 120 min 90%. Midazolam is suitable as an induction agent for shortlasting otorhinolaryngological surgery.

Adolescent

The volatile anesthetics, halothane, enflurane and isoflurane, influence the distribution of thiopental in man differently.

In man, a change of thiopental pharmacokinetics was observed under halothane anesthesia, but not when patients were anesthetized with enflurane and isoflurane. After an initial subanesthetic dose of 50 mg thiopental, the concentrations in serum (T) were determined over 15 min (4 samples). From these T-values the pharmacokinetic parameters Vc (central volume of distribution), t1/2 alpha and Cl were established (control). 16 min after the first thiopental dose, one of the inhalation anesthetics was administered (randomized). After 45 min exposure to the respective inhalation anesthetic (2-3 MAC in combination with N2O, steady-state a second dose of 50 mg thiopental was injected and the T-values were determined again over 15 min. The T-values of the control course varied considerably; the logarithmic frequency distribution revealed two distinct subgroups of patients, A and B, with characteristic Vc and t1/2 alpha. Both subgroups were influenced by the volatile anesthetics in a similar way with regard to pharmacokinetic parameters. With halothane, Vc was decreased and t1/2 alpha was shortened. In contrast, enflurane and isoflurane did not affect the pharmacokinetic parameters.

Adult

Sensitive HPLC assay for thiopental in human serum after simple preparation of the samples. Its application for clinical research.

A simple, precise and sensitive micro method for the determination of thiopental in human serum is presented. After deproteinization with acetonitrile the supernatant was directly injected into a reversed phase HPLC system with UV photometrical detection at 280 nm. The limit for the detection of thiopental was less than 0.1 microgram/ml serum. Time consuming extraction of the serum sample was not necessary. The method can be recommended for clinical routine analysis; its suitability has been demonstrated in several studies.

Chromatography, High Pressure Liquid

Disposition of etofibrate, clofibric and nicotinic acid esters, and their products in dogs.

Etofibrate, the ethylene glycol diester of clofibric and nicotinic acids, on intravenous infusion into dogs, has a terminal half-life of 2 min. The intermediate half-esters, the nicotinate and the clofibrate, have respective terminal half-lives of 4.6 and 1.7 min and appear fleetingly when etofibrate is administered. In contrast to the 42-h terminal half-life of clofibric acid, the other final transformation product, nicotinic acid, shows saturable or dose-dependent pharmacokinetics in dogs that conform to the Michaelis-Menten equation with a terminal half-life of 4.4 min at low concentrations (less than 6.9 microM/kg). Three distinct metabolites of nicotinic acid can be identified and assayed chromatographically in the urine. The partition properties were similar to nicotinic acid. Nicotinic acid is excreted 30% unchanged into urine with a renal clearance of 70 mL/min in 27-kg dogs.

Animals

[The bioavailability of combination preparations of acetylsalicylic acid and codeine phosphate].

Plasma levels time curves of acetylsalicylic acid, salicylic acid, salicyluric acid and codeine were monitored after intravenous, oral and rectal application (single dose) of preparations containing acetylsalicylic acid and codeine. The mean absolute bioavailability of acetylsalicylic acid was 68% after oral application and 60% after rectal application. The corresponding bioavailability data of codeine were 59% and 63%, respectively.

Administration, Oral

[Circadian-induced change in the pharmacokinetic pattern exemplified on hexobarbital/Retrospective analysis of experimental data (author's transl)].

The present study dealt with data from a study to evaluate circadian influences on the pharmacokinetics of hexobarbital. It could be seen that the pharmacokinetic model changes from an open one-compartment model to an open two-compartment model in dependence of the time of application. The curve fitting to an open two-compartment model reached high correlations when the test substance was applied at 18 h. The pharmacokinetic parameters to be evaluated did not fit to literature data. After application of the substance at 10 h in the morning the curve fitting to an open one-compartment model correlated highly. The pharmacokinetic parameters at this time comparable with the known literature.

Circadian Rhythm