PubMed Health⌕ Search

Biomedical subjects

H Stoeckel

Publications and source records attributed to H Stoeckel.

At least 19 recordsLinked to original sources

Plasmalemmal voltage-activated K(+) currents in protoplasts from tobacco BY-2 cells: possible regulation by actin microfilaments?

Plasmalemmal ionic currents from enzymatically isolated protoplasts of suspension-cultured tobacco 'Bright Yellow-2' cells were investigated by whole-cell patch-clamp techniques. In all protoplasts, delayed rectifier outward K(+) currents having sigmoidal activation kinetics, no inactivation, and very slow deactivation kinetics were activated by step depolarization. Tail current reversal potentials were close to equilibrium potential E(K) when external [K(+)] was either 6 or 60 mM. Several channel blockers, including external Ba(2+), niflumic acid, and 5-nitro-2-(3-phenylpropylamino)-benzoic acid, inhibited this outward K(+) current. Among the monovalent cations tested (NH(4)(+), Rb(+), Li(+), Na(+)), only Rb(+) had appreciable permeation (P(Rb)/P(K) (=) 0.7). In addition, in 60 mM K(+) solutions, a hyperpolarization-activated, time-dependent, inwardly rectifying K(+) current was observed in most protoplasts. This inward current activated very slowly, did not inactivate, and deactivated quickly upon repolarization. The tail current reversal potential was very close to E(K), and other monovalent cations (NH(4)(+), Rb(+), Li(+), Na(+)) were not permeant. The inward current was blocked by external Ba(2+) and niflumic acid. External Cs(+) reversibly blocked the inward current without affecting the outward current. The amplitude of the inward rectifier K(+) current was generally small compared to the amplitude of the outward K(+) current in the same cell, although this was highly variable. Similar amplitudes for both currents occurred in only 4% of the protoplasts in control conditions. Microfilament-depolymerizing drugs shifted this proportion to about 12%, suggesting that microfilaments participate in the regulation of K(+) currents in tobacco 'Bright Yellow-2' cells.

Actin Cytoskeleton↗

Mechanism of calcium oscillations in migrating human astrocytoma cells.

Numerous studies show that intracellular calcium controls the migration rate of different mobile cell types. We studied migrating astrocytoma cells from two human cell lines, U-87MG and A172, in order to clarify the mechanisms by which calcium potentially influences cell migration. Using the wound-healing model to assay migration, we showed that four distinct components of migration could be distinguished: (i) a Ca(2+)/serum-dependent process; (ii) a Ca(2+)-dependent/serum-independent process; (iii) a Ca(2+)/serum-independent process; (iv) a Ca(2+)-independent/serum-dependent process. In U-87MG cells which lack a Ca(2+)-dependent/serum-independent component, we found that intracellular Ca(2+) oscillations are involved in Ca(2+)-dependent migration. Removing extracellular Ca(2+) greatly decreased the frequency of migration-associated Ca(2+) oscillations. Furthermore, non-selective inhibition of Ca(2+) channels by heavy metals such as Cd(2+) or La(3+) almost completely abolished changes in intracellular Ca(2+) observed during migration, indicating an essential role for Ca(2+) channels in the generation of these Ca(2+) oscillations. However, specific blockers of voltage-gated Ca(2+) channels, including nitrendipine, omega-conotoxin GVIA, omega-conotoxin MVIIC or low concentrations of Ni(2+) were without effect on Ca(2+) oscillations. We examined the role of internal Ca(2+) stores, showing that thapsigargin-sensitive Ca(2+) stores and InsP(3) receptors are involved in Ca(2+) oscillations, unlike ryanodine-sensitive Ca(2+) stores. Detailed analysis of the spatio-temporal aspect of the Ca(2+) oscillations revealed the existence of Ca(2+) waves initiated at the leading cell edge which propagate throughout the cell. Previously, we have shown that the frequency of Ca(2+) oscillations was reduced in the presence of inhibitory antibodies directed against beta3 integrin subunits. A simple model of a Ca(2+) oscillator is proposed, which may explain how the generation of Ca(2+) oscillations is linked to cell migration.

Astrocytoma↗

Calcium-sensitivity of the plasmalemmal delayed rectifier potassium current suggests that calcium influx in pulvinar protoplasts from Mimosa pudica L. can be revealed by hyperpolarization.

Isolated protoplasts from pulvinar motor cells of Mimosa pudica were studied using conventional whole-cell patch clamp techniques. With internal solutions weakly buffered for Ca2+ (0.2 mM EGTA), a rundown of the outward delayed rectifier K+ current was induced by hyperpolarizing the holding potential, and this effect was strongly promoted by high external Ca2+ concentrations. This rundown could be reversed by coming back to less hyperpolarized holding potentials or by lowering the external [Ca2+]. Such rundown was absent when pipette internal solutions strongly buffered (10 mM EGTA) for Ca2+ were used. Ionomycin induced rundown of the K+ current with internal solutions containing 0.2 mM but not 10 mM EGTA. The hyperpolarization-associated rundown was reversibly blocked by Gd3+ and La3+.

Bepridil↗

Plasmalemmal, voltage-dependent ionic currents from excitable pulvinar motor cells of Mimosa pudica.

Plasmalemmal ionic currents from excitable motor cells of the primary pulvinus of Mimosa pudica were investigated by patch-clamp techniques. In almost all of the enzymatically isolated protoplasts, a delayed rectifier potassium current was activated by depolarization, while no currents were detected upon hyperpolarization. This sustained outward current was reversibly blocked by Ba and TEA and serves to repolarize the membrane potential. Outward single channel currents that very likely underly the macroscopic outward potassium current had an elementary conductance of approximately 20 pS. In addition, in a few protoplasts held at hyperpolarized potentials, depolarization-activated transient inward currents were observed, and under current clamp, action potential-like responses were triggered by depolarizing current injections or by mechanical perturbations. The activation characteristics of both inward currents and spikes showed striking similarities compared to those of action potentials in situ.

Barium↗

Closed-loop feedback controlled administration of alfentanil during alfentanil-nitrous oxide anaesthesia.

We have studied the automatic administration of alfentanil during alfentanil-nitrous oxide anaesthesia in 11 patients using a closed-loop feedback control system based on EEG analysis. We chose a median EEG frequency of 2-4 Hz as the EEG set point. The slope of the asymptote to the cumulative dose requirement was used to define an effective therapeutic infusion of alfentanil. Median EEG frequency (mean (SD)) during the feedback period was 3.03 (0.45) Hz. The average effective therapeutic infusion of alfentanil was 0.140 (0.032) mg min-1. We conclude that EEG feedback control may be useful in assessing and defining the dose requirements of alfentanil.

Adult↗

[Systematics and concept of a future integrated anesthesia device].

On the grounds of the more than one hundred years lasting development of the anaesthesia machine the systematics of the components of a future integrated anaesthesia machine is described. The new generation of today's anaesthesia machine incorporates four main functions: dosing, ventilation, monitoring and data management. Given the achievements of the last 15 years in the fields of data and signal analysis, of the clinical pharmacology of intravenous anaesthetics, of measurement and evaluation of anaesthetic drug action, the four main functions are only partially realized in today's anaesthesia machines. Especially lacking are the integration of smart dosing devices for intravenous anaesthetics, the so-called "therapeutic monitoring" which monitors the efficacy of anaesthetic drug action, and a data management system which does not only manage data but interprets them in terms of "smart alarms" and maybe in the future also by expert systems. The concept of a future integrated anaesthesia machine is investigated via a study model and on the basis of a real model composed of already existing devices.

Anesthesiology↗

Influence of the pulmonary circulation on adrenaline pharmacokinetics during cardiopulmonary resuscitation.

The influence of the pulmonary circulation on the pharmacokinetics and -dynamics of endogenously released, and intravenously injected (10 micrograms kg-1), and endobronchially (e.b.) administered (100 micrograms kg-1) adrenaline was investigated in an animal cardiopulmonary-resuscitation (CPR) model. During resuscitation 80% of endogenously released and i.v. adrenaline was eliminated before reaching the arterial circulation, whereas arterial availability of adrenaline was higher than mixed-venous availability in the e.b.-medicated animals. Success of resuscitation seemed to depend on maximum adrenaline concentrations and drug availability in arterial blood. Although the average amount of endogenously released adrenaline was calculated to be equivalent to an i.v. bolus of 8 micrograms kg-1, additional i.v. or e.b. adrenaline medication resulted in higher arterial plasma concentrations, improved circulation during CPR, and better resuscitability. It is concluded that, even without a specific pulmonary metabolism, a drastic decrease in blood flow can lead to significant arterio-venous gradients in plasma concentrations and availability of a drug with a very high clearance like adrenaline.

Administration, Inhalation↗

[O2 uptake and CO2 production during total intravenous propofol-alfentanil anesthesia under steady-state conditions. Is O2 uptake a parameter for assessing the depth of anesthesia?].

Depending on surgical and anaesthesiological procedures, anaesthesia leads to a reduction of O2 uptake (VO2), CO2 production (VCO2) and resting energy expenditure (REE). A controversial discussion on the degree of metabolic depression has continued in the literature fueled by a lack of studies in patients under standardised conditions. The goal of this study was to evaluate whether O2 consumption and/or CO2 production can be correlated to various depths of anaesthesia and whether VO2 could be a parameter to control narcosis. 12 patients (ASA I-II) scheduled for urological surgery of the lower abdomen, were given total intravenous anaesthesia with propofol and alfentanil. During a 60 minutes period the patients were first anaesthesized with an ED50 and then titrated to a dosage correlating with an ED95. The premedicated but awake patients each showed a REE which was about 10% below the calculated basal metabolism. Steady-state general anaesthesia led to an approximately 30% reduction of VO2, VCO2 an REE. Patients with adequate anaesthesia revealed no changes in oxidative metabolism with increased or decreased depth of anaesthesia. VO2 as a leading parameter proves to be problematic. It is useful as a measure for insufficient depth of general anaesthesia but fails to indicate overshooting anaesthesia depth.

Adult↗

Effective therapeutic infusions produced by closed-loop feedback control of methohexital administration during total intravenous anesthesia with fentanyl.

A combined pharmacokinetic and pharmacodynamic model of methohexital was used to establish and evaluate feedback control of methohexital delivery during total intravenous anesthesia with fentanyl in 11 surgical patients. The median frequency of the EEG power spectrum served as the pharmacodynamic variable constituting feedback. Based on previous investigations a median frequency from 2-3 Hz was chosen as the desired EEG set point. In addition to methohexital, patients were given a 10-min loading infusion of 0.5 mg of fentanyl followed by a constant-rate infusion of 0.22 mg/h. In agreement with an earlier similar study in volunteers given only methohexital and aiming at the same set point, identical distribution of EEG power was achieved in the current study. The decrease of median EEG frequency to 2-3 Hz was primarily induced by an increase in fractional power in the 0.5-2- Hz frequency band to 46 +/- 4%. The average requirement of methohexital during the first 2 h was 675 +/- 250 mg. The authors conclude that model-based feedback control of intravenous methohexital delivery can help establish and quantitate methohexital requirements during total intravenous anesthesia with fentanyl.

Adolescent↗

[Interdisciplinary computerized evaluation of perioperative risk factors].

The identification and assessment of perioperative risk factors combined with interdisciplinary management may lead to minimized risk for the patient. The numerous medical and administrative data should be collected by a computer. This was done in a preliminary study at the university of Bonn, where 9772 anaesthesias given for general surgery were evaluated. The necessary outcome studies should be based on statistical evaluation of the data (factor analysis) and their interpretation should be an interdisciplinary concern.

Adolescent↗