Search PubMed⌕ Search

Biomedical subjects

E Kochs

Publications and source records attributed to E Kochs.

At least 37 records · Page 2Linked to original sources
PubMed2001

Open channel and competitive block of nicotinic receptors by pancuronium and atracurium.

Mouse myotubes were used to investigate effects of the nondepolarizing neuromuscular blocking drugs pancuronium and atracurium on embryonic-type nicotinic acetylcholine receptor channels. Experiments were performed using patch-clamp techniques in combination with devices for ultra-fast solution exchange at outside--out patches. Application of 0.1 mM acetylcholine resulted in a fast current transient. When the peak amplitude was achieved, the current decayed monoexponentially due to desensitization. After application of drugs (pancuronium or atracurium), two different mechanisms of block were observed: (1) open channel block of embryonic-type nicotinic acetylcholine receptor channels after coapplication of blocker and acetylcholine, characterized by decrease of the time constant of current decay; (2) competitive block of embryonic-type nicotinic acetylcholine receptor channels by pancuronium or atracurium after preincubation of outside-out patches with the respective blocker. Different affinities of pancuronium (K(B) approximately 0.01 microM) and atracurium (K(B) approximately 1 microM) to embryonic-type nicotinic acetylcholine receptor channels were observed.

Acetylcholine↗
PubMed2001

S(+)-ketamine/propofol maintain dynamic cerebrovascular autoregulation in humans.

PURPOSE: This study investigates the effects of S(+)-ketamine and propofol in comparison to sevoflurane on dynamic cerebrovascular autoregulation in humans. METHODS: Twenty-four patients were randomly assigned to one of the following anesthetic protocols: group I (n=12): 2.5 mg.kg(-1)*hr(-1) S(+)-ketamine, 1.5-2.5 microg*mL(-1) propofol-target plasma concentration; group II (n=12): 2.0 MAC (4.0 %) sevoflurane. Patients were intubated and ventilated with O(2)/air (PaO(2)=0.33). Following 40 min of equilibration dynamic cerebrovascular autoregulation was measured and expressed as the autoregulatory index (ARI), describing the duration of cerebral hemodynamic recovery in relation to changes in mean arterial blood pressure. STATISTICS: Mann-Whitney U test (statistical significance was assumed when P <0.05). RESULTS: Dynamic cerebrovascular autoregulation was intact in all patients with S(+)-ketamine/propofol anesthesia as indicated by an ARI of 5.4 +/- 1.1. In contrast, dynamic cerebrovascular autoregulation was significantly delayed with 2.0 MAC sevoflurane (ARI=2.6 +/- 0.7) CONCLUSION: Dynamic cerebrovascular autoregulation is maintained with S(+)-ketamine/propofol-based total iv anesthesia. In contrast, 2.0 MAC sevoflurane delayed dynamic cerebrovascular autoregulation. This supports the use of S(+)-ketamine in combination with propofol in neurosurgical patients based on its neuroprotective potential along with maintained cerebrovascular physiology.

Adult↗
PubMed2001

Long-term depression in the basolateral amygdala of the mouse involves the activation of interneurons.

Long-term depression (LTD) in the basolateral amygdala, following low frequency stimulation (1 Hz/900 pulses) of the lateral amygdala, was studied in an in vitro slice preparation of 2-3 weeks and 2-4 months old mice. Whole-cell patch-clamp recordings of neurons, visualized by means of infrared videomicroscopy, and extracellular field potential recordings were performed. Loading single neurons with the calcium chelator BAPTA (30 mM) did not reduce the excitatory postsynaptic currents following low frequency stimulation. However, buffering presynaptic calcium with BAPTA-AM, and application of the specific Ca2+/calmodulin-stimulated protein kinase II antagonist KN-62 (1-[N,O-bis(5-isoquinoline sulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperizine), blocked low frequency stimulation-induced LTD. The induction of LTD was reduced by the competitive N-methyl-D-aspartate receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (50 microM), and blocked by the metabotropic glutamate receptor antagonist (-)-amino-4-carboxy-methyl-phenylacetic acid (1 mM), and by 5-hydroxytryptamine (5-HT; 30 microM) via the activation of 5-HT(1A) receptors. Also blocking GABA(A) receptor-mediated synaptic transmission with bicuculline (10 microM) or picrotoxin (20 microM) reduced the induction of LTD. Visually and electrophysiologically identified interneurons in slices from 2 weeks old mice, expressed in contrast to adult mice (2-4 months), pronounced LTD. Principal neurons showed only weak LTD after low frequency stimulation.A synopsis of these findings suggests a pivotal role of GABAergic interneurons and serotonergic afferents in the induction of LTD in the basolateral nucleus of the amygdala.

Aging↗
PubMed2001

Effects of remifentanil/propofol in comparison with isoflurane on dynamic cerebrovascular autoregulation in humans.

BACKGROUND: This study investigates the effects of remifentanil and propofol in comparison to isoflurane on dynamic cerebrovascular autoregulation in humans. METHODS: In 16 awake patients dynamic cerebrovascular autoregulation was measured using transcranial Doppler sonography (TCD). Thereafter patients were intubated, ventilated with O2/air (FiO2=0.33) and randomly assigned to one of the following anesthetic protocols: group 1 (n=8): 0.5 microg x kg(-1) x min(-1) remifentanil combined with a propofol-target plasma concentration of 1.5 microg x ml(-1) group 2 (n=8): 1.8 % isoflurane (1.5 MAC). Following 20 min of equilibration the autoregulatory challenge was repeated. Arterial blood gases and body temperature were maintained constant over time. STATISTICS: Mann-Whitney U-test and Wilcoxon signed-rank test. RESULTS: Dynamic autoregulation was intact in all patients prior to induction of anesthesia expressed by an autoregulatory index (ARI) of 5.4+/-1.21 (mean+/-SD, group 1) and 5.9+/-0.98 (mean+/-SD, group 2). With remifentanil/propofol anesthesia dynamic autoregulation was similar to the awake state (group 1: ARI=4.9+/-0.88). In contrast, autoregulatory response was delayed with 1.5 MAC isoflurane (group 2, ARI=2.1+/-0.92) (P<0.05). CONCLUSION: These data show that dynamic cerebrovascular autoregulation is maintained with remifentanil-based total intravenous anesthesia. This is consistent with the view that narcotics (and hypnotics) do not alter the physiologic cerebrovascular responses to changes in MAP. In contrast, 1.5 MAC isoflurane delays cerebrovascular autoregulation compared to the awake state.

Adult↗
PubMed2001

Sevoflurane potentiates and blocks GABA-induced currents through recombinant alpha1beta2gamma2 GABAA receptors: implications for an enhanced GABAergic transmission.

BACKGROUND AND OBJECTIVE: The gamma-aminobutyric acidA receptor (GABAAR) is a target for anaesthetic agents. We investigated the interactions of sevoflurane with a recombinant GABAAR. Emphasis was on the mechanism of block, as relevant open-channel block by a volatile anaesthetic would possibly explain prolonged GABAergic postsynaptic currents. METHODS: The effect of sevoflurane on GABA-induced currents through recombinant alpha1beta2gamma2 GABAAR channels was studied (patch clamp; HEK293 cells). GABA 0.01 mM or 1 mM was applied alone or together with sevoflurane (0.05 mM to 5 mM). RESULTS: Currents elicited by GABA 0.01 mM were increased by low sevoflurane concentrations to 183% and decreased by high sevoflurane concentrations (> 1 mM) to 34% (P < 0.05). Ten- to 90%-rise times of the currents were reduced by sevoflurane concentration dependently. At GABA (1 mM), peak currents and 10-90%-rise times decreased with increasing sevoflurane concentrations. A transient current increase was induced by discontinuation of GABA and sevoflurane. Such rebound currents indicate a reversal of an open-channel block by sevoflurane. CONCLUSIONS: Sevoflurane (a) increases the apparent affinity of GABA to the GABAAR, as suggested by the decreased current rise times. This explains the enhancement of the currents induced by low GABA concentrations (0.01 mM). Additionally, sevoflurane (b) induces a picrotoxin-like open-channel block at the GABAAR. The reversal of the open-channel block elicits a delayed GABA response. These findings indicate at least two different sites of action of sevoflurane at this receptor that are both important for an enhanced GABAergic synaptic transmission.

Anesthetics, Inhalation↗
PubMed2001

Small-dose S(+)-ketamine reduces postoperative pain when applied with ropivacaine in epidural anesthesia for total knee arthroplasty.

UNLABELLED: Reduction of nociceptive input through blockade of N-methyl-D-aspartate (NMDA) receptors has been reported. We compared the effects of epidural S(+)-ketamine versus placebo on postoperative pain in a randomized, double-blinded study in 37 patients undergoing unilateral knee arthroplasty. After lumbar epidural anesthesia with ropivacaine (10 mg/mL, 10-20 mL), 19 patients received 0.9% epidural saline, and 18 patients received 0.25 mg/kg epidural S(+)-ketamine 10 min before surgical incision. After surgery, patient-controlled epidural analgesia with ropivacaine was provided. During the first 8 h after surgery, visual analog scale pain rating was similar between groups. Twenty-four and 48 h after surgery, patients anesthetized with ropivacaine had higher visual analog scale ratings at rest and during movement (P < 0.05) than patients anesthetized with S(+)-ketamine and ropivacaine. Forty-eight hours after surgery, patients anesthetized with ropivacaine also consumed more ropivacaine (558 +/- 210 mg) (P < 0.01) than those anesthetized with S(+)-ketamine and ropivacaine (319 +/- 204 mg). Adverse events were similar between groups. Patients who received S(+)-ketamine and ropivacaine rated the quality of their pain therapy better than those who received ropivacaine alone (P < 0.05). We conclude that the combination of S(+)-ketamine and ropivacaine in epidural anesthesia increases postoperative pain relief when compared with ropivacaine. IMPLICATIONS: Epidural S(+)-ketamine applied with ropivacaine before surgery is a rational approach to decrease injury-induced pain sensitization. Epidural blockade with an N-methyl-D-aspartate receptor antagonist and a local anesthetic may provide better analgesia in the postoperative period than a local anesthetic alone.

Aged↗
PubMed2001

Local GABA(A) receptor blockade reverses isoflurane's suppressive effects on thalamic neurons in vivo.

Many in vitro effects of volatile anesthetics are known, but the mechanisms of action are still under debate. Because suppression of sensory perception is one of the major goals of general anesthesia, we studied the effects of isoflurane on the processing of somatosensory information in anesthetized rats. Local iontophoretic administration of the gamma-aminobutyric acid-A (GABA(A)) receptor antagonist bicuculline in the thalamic ventral posteromedial nucleus reversed suppressive effects of isoflurane on thalamocortical relay neurons (TCNs). The action potential discharges of TCNs (n = 23) in response to defined mechanical stimulation of receptive fields seen with small concentrations of isoflurane (0.79% +/- 0.01%, mean +/- SEM) were suppressed under large concentrations (1.44% +/- 0.04%). In addition, the tonic response pattern was lost, which initially encoded the information about the stimulus features. In 70% of TCNs, bicuculline administration reestablished the initially present tonic response pattern under large isoflurane concentrations. These results indicate that isoflurane suppresses somatosensory information transfer at the thalamic level in vivo, apparently by enhancing thalamic GABA(A) receptor-mediated inhibition.

Anesthetics, Inhalation↗
PubMed2001

Isoflurane blocks synaptic plasticity in the mouse hippocampus.

BACKGROUND: The volatile anesthetic isoflurane depresses glutamatergic transmission. In this study, the authors investigated the effects of isoflurane on the induction of long-term potentiation (LTP) and long-term depression (LTD) in slices from the juvenile and adult mouse hippocampus. Both forms of synaptic plasticity involve the activation of glutamate receptors. METHODS: Field excitatory postsynaptic potentials and excitatory postsynaptic currents from neurons in the CA1 area were evoked by stimulation of the Schaffer collateral-commissural pathway. Two independent synaptic inputs were stimulated. Clinically relevant concentrations (0.2-0.3 mM) of isoflurane were added to the perfusion solution. RESULTS: Field excitatory postsynaptic potentials from slices of juvenile and adult mice were depressed to 37.3 +/- 6.1% and 58.3 +/- 7.4%, respectively, and excitatory postsynaptic currents were reduced to 36.7 +/- 5.4% by isoflurane. A brief tetanic stimulation (100 Hz, 1 s) induced stable LTP of field excitatory postsynaptic potentials. In the presence of isoflurane, tetanization failed to induce LTP. The effect of isoflurane on LTP induction was reversible and could be prevented by antagonizing gamma-aminobutyric acid type A receptors (GABAA). Low-frequency stimulation (1 Hz/900 pulses) induced LTD. In the presence of isoflurane, low-frequency stimulation failed to induce LTD. CONCLUSIONS: The prevention of the isoflurane-induced depression of LTP by the GABAA antagonist picrotoxin suggests an involvement of GABAA receptors. An enhancement of the efficacy of GABA-mediated inhibitory synaptic transmission prevents the depolarization of the postsynaptic membrane during tetanus, necessary for the induction of use-dependent alteration of synaptic strength. An impairment of these processes may be a cause for the transient loss of recall and cognitive impairment after anesthesia in juvenile and adult brains.

Aging↗
PubMed2001

Wavelet analysis of middle latency auditory evoked responses: calculation of an index for detection of awareness during propofol administration.

BACKGROUND: Middle latency auditory evoked responses (MLAER) as a measure of depth of sedation are critically dependent on data quality and the analysis technique used. Manual peak labeling is subject to observer bias. This study investigated whether a user-independent index based on wavelet transform can be derived to discriminate between awake and unresponsive states during propofol sedation. METHODS: After obtaining ethics committee approval and written informed consent, 13 volunteers and 40 patients were studied. In all subjects, propofol was titrated to loss of response to verbal command. The volunteers were allowed to recover, then propofol was titrated again to the same end point, and subjects were finally allowed to recover. From three MLAER waveforms at each stage, latencies and amplitudes of peaks Pa and Nb were measured manually. In addition, wavelet transform for analysis of MLAER was applied. Wavelet transform gives both frequency and time information by calculation of coefficients related to different frequency contents of the signal. Three coefficients of the so-called wavelet detail level 4 were transformed into a single index (Db3d4) using logistic regression analysis, which was also used for calculation of indices for Pa, Nb, and Pa/Nb latencies. Prediction probabilities for discrimination between awake and unresponsive states were calculated for all MLAER indices. RESULTS: During propofol infusion, subjects were unresponsive, and MLAER components were significantly depressed when compared with the awake states (P < 0.001). The wavelet index Db3d4 was positive for awake and negative for unresponsive subjects with a prediction probability of 0.92. CONCLUSION: These data show that automated wavelet analysis may be used to differentiate between awake and unresponsive states. The threshold value for the wavelet index allows easy recognition of awake versus unresponsive subjects. In addition, it is independent of subjective peak identification and offers the advantage of easy implementation into monitoring devices.

Adult↗
PubMed2001

Hypertonic-hyperoncotic saline differentially affects healthy and glutamate-injured primary rat hippocampal neurons and cerebral astrocytes.

Hypertonic-hyperoncotic saline solutions (HHS) have been used for small-volume resuscitation and to treat intracranial hypertension and cerebral edema in neurocritical care. Little is known on the response of brain cells to direct exposure in HHS, which may occur in blood-brain barrier disruption. We studied the effects of HHS on healthy and glutamate-injured brain cells in vitro. To model a hypertonic-hyperoncotic environment, rat hippocampal neurons and cerebral astrocytes were exposed to hypertonic saline and hydroxyethyl starch (HES) added to medium for 15 minutes (final osmolarity: 350 mOsm/L in the neuronal, 373 mOsm/L in the glial medium; 2.5 mg/mL HES in both media). To simulate excitotoxicity, cells were exposed to 100 microM glutamate for 8 minutes before exposure to HHS. Cell viability was analyzed by morphology and vital dye staining; intracellular water space (WS) and glucose use were measured by scintillation spectrometry using 3-O-methyl[14C]-D-glucose and [3H]2-deoxy-D-glucose ([3H]2-DG). After 24 hours, exposure to HHS added to medium caused a 30% reduction in viability of healthy neurons (P < .05), but did not exacerbate the glutamate-induced 50% decrease in neuronal survival. One hundred percent astrocyte viability remained unchanged. The WS of astrocytes and surviving neurons was negligibly altered. Exposure to HHS added to medium caused a 35% reduction in [3H]2-DG in healthy and glutamate-injured neurons (P < .05), but did not affect [3H]2-DG in astrocytes. Our data show that HHS may potentially injure hippocampal neurons. Preserved WS values imply that live cells maintained volume regulation capabilities, indicating a lack of dehydration 24 hours after exposure to HHS. Impaired glucose use predisposes neurons to disturbed metabolism, which may influence neuronal outcome after brain injury.

Animals↗
PubMed2001

Coadministered nitrous oxide enhances the effect of isoflurane on GABAergic transmission by an increase in open-channel block.

Clinically relevant concentrations of isoflurane (ISO) and nitrous oxide (N2O) enhance chloride currents induced by activating gamma-aminobutyric acid(A) receptors (GABA(A)R). Channel blocking by ISO overcomes the enhancing effect at higher concentrations. In this study, the effect of coadministered ISO and N2O on responses evoked by GABA in transfected human embryonic kidney 293 cells carrying alpha1beta2gamma2L GABA(A)R was investigated. Patch-clamp recordings from these cells were performed in the whole cell mode. A piezo-driven "liquid filament" drug application system was used to apply solutions of GABA, ISO, and N2O. Increasing the concentration of ISO in steps from 0.15 to 1.2 mM resulted in a bell-shaped concentration-response curve for GABA-induced currents. The maximum increase in current (1.51 +/- 0.14-fold) was seen at 0.45 mM ISO (about 1 minimum alveolar concentration, EC50). N2O (29.2 mM) increased GABA-evoked currents 1.54 +/- 0.10-fold. The enhancing effects of ISO and N2O on the GABAergic response were not additive. However, a transient current, associated with the rapid withdrawal of ISO from the receptor, was markedly increased by N2O. Such rebound currents probably reflect the transition from a "channel-blocked" to a "reopened" state. An open-channel block at ligand-gated receptors can prolong postsynaptic currents. Thus, we conclude that coadministered N2O could increase the enhancing effect of ISO on the GABAergic transmission by an increase in open-channel block at the GABA(A)R.

Anesthetics, Inhalation↗
PubMed2000

[Metformin-induced lactic acidosis].

HISTORY AND ADMISSION FINDINGS: A 62-year-old woman had been found unconscious on her bed. She had to be resuscitated several times in the ambulance on the way to hospital. On admission her pupils were dilated and fixed, the cardiovascular system was unstable. Her rectal temperature was 28 degrees C. She was a diabetic being treated with metformin and glimepiride and was in incipient renal failure (serum creatinine 1.5 mg/dl). She was also in heart failure due to coronary heart disease and was in a debilitated state. INVESTIGATIONS: She had marked lactic acidosis (lactate 45.3 mmol/l; pH 6.6). Toxicological screening tests were negative. TREATMENT AND COURSE: In the absence of a history she was at first treated symptomatically. Conventional management of the lactic acidosis neither corrected the acidosis nor stabilized the circulatory system. Continuous veno-venous haemodialysis with bicarbonate-buffered solutions succeeded in reducing the need for catecholamines. Neurological examination was supplemented by recording acoustic and sensory evoked potentials. Suspected metformin-induced lactic acidosis was confirmed by appropriate tests. Three weeks after admission she was well enough to be transferred to a normal medical ward and ultimately discharged without further complications. CONCLUSION: Metformin should only be prescribed if the contraindications, in particular renal failure are carefully monitored. Severe lactic acidosis should be treated early with continuous veno-venous haemodialysis with bicarbonate-buffered substituting fluids. The good neurological results in this case are probably largely due to the marked hypothermia.

Acidosis, Lactic↗
PubMed2000

High-dose S(+)-ketamine improves neurological outcome following incomplete cerebral ischemia in rats.

PURPOSE: To determine the effects of the non-competitive NMDA-receptor antagonist S(+)-ketamine on neurological outcome in a rat model of incomplete cerebral ischemia. METHODS: Thirty rats were anesthetized, intubated and mechanically ventilated with isoflurane, O2 30% and nitrous oxide 70%. Following surgery animals were randomly assigned to one of the following treatment groups: Rats in group 1 (n = 10,OFF control) received fentanyl (bolus: 10 microg x kg(-1) i.v.; infusion 25 microg x kg(-1) x h(-1)) and N2O 70% / O2. Rats in group 2 (n = 10) received O2 30% in air and low-dose S(+)-ketamine (infusion: 0.25 mg x kg(-1) x min(-1)). Rats in group 3 (n = 10) received O2 30% in air and high-dose S(+)-ketamine (infusion: 1.0 mg x kg(-1) min(-1)). Following 30 min equilibration period ischemia was induced by combined unilateral common carotid artery ligation and hemorrhagic hypotension to 35 mm Hg for 30 min. Plasma catecholamines were assayed before and at the end of ischemia. Neurological deficit was evaluated for three postischemic days. RESULTS: Neurological outcome was improved with high-dose S(+)-ketamine when compared to fentanyl / N2O -anesthetized controls (9 vs. 1 stroke related deaths, P<0.05). Increases in plasma catecholamine concentrations were higher in fentanyl / N2O -anesthetized (adrenaline baseline 105.5+/-92.1 pg x ml(-1), during ischemia 948+/-602.8 pg x ml(-1), P<0.05; noradrenaline baseline 407+/-120.2 pg x ml(-1), ischemia 1267+/-422.2 pg x ml(-1), P <0.05) than in high-dose S(+)-ketamine-treated animals (adrenaline baseline 71+/-79.5 pg x ml(-1), ischemia 237 +/-131.9; noradrenaline baseline 317.9+/-310.5 pg x ml(-1), ischemia 310.5+/-85.7 pg x ml(-1)). CONCLUSION: Neurological outcome is improved following incomplete cerebral ischemia with S(+)-ketamine. Decreases in neuronal injury may be related to suppression of sympathetic discharge.

Animals↗
PubMed2000

[The neuroprotective effect of the glutamate antagonist acamprosate following experimental cerebral ischemia. A study with the lipid peroxidase inhibitor u-101033e].

INTRODUCTION: This study investigates the effects of acamprosate, a glutamatergic modulator, and the lipid peroxidation inhibitor U-101033E on neurological outcome following incomplete cerebral ischemia and reperfusion in rats. MATERIAL AND METHODS: Twenty-seven male Sprague-Dawley rats were randomly assigned to one of the following treatment groups: 1 (n = 9, control, no drug treatment), 2 (n = 9, 2 x 200 mg/kg acamprosate i.p.), and 3 (n = 9, 2 x 0.3 mg/kg U-101033E i.v.). Background anesthesia was maintained using a combination of fentanyl and O2/N2O (FiO2 = 0.3). Ischemia was produced by combined unilateral common carotid artery ligation and hemorrhagic hypotension to a mean arterial blood pressure (MAP) of 35 mm Hg for 30 minutes. Functional neurological deficit was evaluated for the following 3 days after cerebral ischemia. RESULTS: At the third postischemic day, five control animals and five animals treated with U-101033E were dead for stroke-related reasons. Surviving animals presented severe neurological deficits. In contrast, acamprosate improved neurological outcome, with stroke-related death occurring in one animal only and a minor neurological deficit in the surviving rats. DISCUSSION: The present study demonstrates that acamprosate, in contrast to U-101033E, significantly reduces neurological deficits following transient hemispheric ischemia. The neuroprotective mechanisms of acamprosate may be related to its antiglutamatergic effect with consecutive reduction of transmembraneous Ca++ flux through NMDA-activated ion channels.

Acamprosate↗