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Biomedical subjects

E Kochs

Publications and source records attributed to E Kochs.

At least 19 recordsLinked 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↗
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↗
PubMed2000

Increasing isoflurane concentration may cause paradoxical increases in the EEG bispectral index in surgical patients.

We have studied the effects of increases in isoflurane concentration on the EEG bispectral index (BIS) in 70 patients anaesthetized with isoflurane-nitrous oxide-sufentanil for major abdominal surgery. During surgery, baseline BIS was recorded at 0.8% end-tidal isoflurane with nitrous oxide in oxygen (FIO2 0.35). After this, end-tidal isoflurane was increased to 1.6% for 15 min and decreased subsequently to 0.8% for 20 min to assess recovery. In 20 patients, BIS decreased from a mean value of 40 (SD 9) during baseline to 25 (10) at 1.6% isoflurane. In contrast, BIS did not change in 23 patients and increased in 27 patients from 35 (6) to 46 (8) as isoflurane was increased to 1.6%. In all patients, BIS recovered to baseline values at 0.8% isoflurane. The changes in BIS with increasing isoflurane concentration were not related to drugs or differences in physiological variables, which did not differ between groups. Patients with a decrease in BIS were significantly younger (38 (range 18-68) yr) than those with unchanged (55 (26-70) yr) or increased (60 (40-70) yr) BIS values (P < 0.001). It is possible that the paradoxical increase in BIS is related to continuous pre-burst EEG patterns consisting of high-frequency activity. This suggests that the use of BIS as a guide for isoflurane administration may be misleading in some patients undergoing surgical procedures.

Abdomen↗
PubMed2000

Postoperative pain management and recovery after remifentanil-based anaesthesia with isoflurane or propofol for major abdominal surgery. Remifentanil Study Group.

We have assessed if recovery times after morphine or fentanyl, given before terminating remifentanil anaesthesia with isoflurane or propofol, are compromised. We studied patients undergoing elective, major abdominal surgery, allocated randomly to receive remifentanil and isoflurane (n = 277) or remifentanil and propofol (n = 274) anaesthesia. Twenty-five minutes before the end of surgery, patients received fentanyl 0.15 mg or morphine 15 mg in a randomized, double-blind manner followed by a second dose (fentanyl 0.05 mg, morphine 7 mg) for moderate or severe pain in recovery. Recovery was rapid and at an Aldrete score > or = 9 (median 12-15 min), 42-51% of patients reported none or mild pain. However, 26-35% of patients reported severe pain and > 90% required a second dose of opioid within 21-27 min after anaesthesia.

Abdomen↗
PubMed2000

Effects of xenon on cerebral blood flow and autoregulation: an experimental study in pigs.

We have investigated the effects of xenon on regional cerebral blood flow (rCBF) and autoregulation in pigs sedated with propofol 4 mg kg-1 h-1. Balloon-tipped catheters were placed into the descending aorta and inferior vena cava of 15 Göttingen Minipigs for manipulation of arterial pressure and blood sampling. rCBF was measured using the sagittal sinus outflow technique. Xenon was adjusted randomly to end-tidal fractions (FE'Xe) of 0, 0.30, 0.50 and 0.70. After baseline measurements of heart rate (HR), mean arterial pressure (MAP), rCBF, sagittal sinus pressure (SSP) and calculation of regional cerebrovascular resistance (rCVR) at each respective FE'Xe, autoregulation was tested in the MAP range 60-120 mm Hg. Increasing FE'Xe had no effect on HR, MAP, rCBF or SSP. rCVR increased with increases in MAP, regardless of FE'Xe. Autoregulation was not impaired. We conclude that xenon inhalation had no effect on rCBF and autoregulation in our model, which could suggest that xenon is an adequate adjunct for neurosurgical anaesthesia.

Anesthetics, Inhalation↗
PubMed2000

Dual action of isoflurane on the gamma-aminobutyric acid (GABA)-mediated currents through recombinant alpha(1)beta(2)gamma(2L)-GABA(A)-receptor channels.

Isoflurane (ISO) increased the agonist-induced chloride flux through the gamma-aminobutyric acid A receptor (GABA(A)R). This may reflect an anesthetic-induced increase in the apparent agonist affinity. A dual effect of anesthetics was postulated for both the nicotinic acetylcholine receptor (nAChR) and the GABA(A)R. We tested the hypothesis that, in addition to a blocking effect, ISO increases gamma-aminobutyric acid (GABA)-gated currents through recombinant GABA(A)R channels. HEK293 cells were transfected with rat cDNA for alpha(1),beta(2),gamma(2L) subunits. Currents elicited by 1 mM or 0. 01 mM GABA, respectively, alone, or with increasing concentrations of ISO, were recorded by using standard patch clamp techniques. ISO reduced the peak current elicited by 1 mM GABA. Currents induced by 0.01 mM GABA were potentiated by small ISO (twofold at 0.5 mM ISO) and inhibited by larger concentrations. Withdrawal of ISO and GABA induced rebound currents, suggesting an open-channel block by ISO. These currents increased with increasing concentrations of ISO. At large concentrations of ISO, the inhibitory effect predominated and was caused by, at least partly, an open-channel block. At small concentrations of ISO, potentiation of the GABA-gated currents was more prominent. This dual action of ISO indicates different binding sites at the GABA(A)R. The balance between potentiation and block depends on the concentrations of both ISO and GABA.

Anesthetics, Inhalation↗
PubMed2000

Nitrous oxide and xenon increase the efficacy of GABA at recombinant mammalian GABA(A) receptors.

We investigated the interactions between recombinant gamma-aminobutyric acid receptor complex (GABA(A)R) and nitrous oxide (N(2)O) or xenon (Xe). Human embryonic kidney cells (HEK 293) were transfected with rat cDNA for alpha(1)beta(2)gamma(2L) or for alpha(1)beta(2) recombinant GABA(A)R subunits. Patch clamp techniques were used in the whole-cell mode to evaluate the effect of N(2)O and Xe on GABA-induced currents. A piezo-driven "liquid filament switch" was used for fast application. Both N(2)O (100%, 29.2 mM) and Xe (100%, 3.9 mM) reversibly increased GABA-induced currents through the alpha(1)ss(2)gamma(2L) and the alpha(1)beta(2) GABA(A)R channels. The potentiating effect of N(2)O or Xe on peak currents was prominent at small GABA concentrations (10(-7) to 10(-5) M). The addition of N(2)O or Xe increased the efficacy of GABA (10(-7) to 10(-3) M). Both N(2)O and Xe significantly decreased the risetime((10%-90%)) of the currents elicited by small GABA concentrations. At the concentrations used, neither N(2)O nor Xe had an intrinsic effect. We conclude that, similar to other anesthetics, both N(2)O and Xe increase the efficacy of GABA at the GABA(A)R and enhance inhibitory GABAergic synaptic transmission.

Anesthetics, Inhalation↗
PubMed2000

Cerebral histopathology following portal venous infusion of bacteria in a chronic porcine model.

BACKGROUND: The aim of this study was to histologically investigate brain damage after prolonged periods of bacteremia in pigs. METHODS: Twenty-one pathogen-free Göttingen minipigs were anesthetized and instrumented with a femoral arterial, a pulmonary arterial, and through midline abdominal incision with a portal venous catheter. After craniotomy the superior sagittal sinus was cannulated. A lumbosacral spinal catheter was inserted for sampling of cerebrospinal fluid. Twelve hours after instrumentation, the animals were randomized in two groups: septic and control animals. The septic group received an infusion of 107 colony-forming units per kilogram of living Escherichia coli over 0.5 h through portal venous catheter each day. The control group received saline. Postoperative intensive care treatment included 4 days of controlled mechanical ventilation, sedation, and intravenous nutrition. The brains then were removed, fixed, and processed for histology. Each pathologic alteration found in the samples was assessed and given a severity code (0-3). RESULTS: Sham-operated animals showed no alterations caused by the instrumentation and the intensive care treatment. The septic group showed typical clinical signs of sepsis. Vasopressor support and mechanical ventilation prevented systemic hypotension and hypoxemia. High serum and cerebrospinal fluid levels of interleukin-6 and tumor necrosis factor-alpha were detected. The septic group showed severe histologic abnormalities of the brain including perivascular edema, spongiform degeneration, hyperemia, and purpura. Damage of neurons was seen including eosinophilic cytoplasm, shrunken nuclei, and disintegration of the nuclear membrane. CONCLUSIONS: Abdominal sepsis induced severe brain damage that was not related to systemic hypoxia or ischemia. High cerebrospinal fluid levels of tumor necrosis factor-alpha and interleukin-6 were related to an inflammatory process in the brain resulting in cerebral edema and death of neurons.

Animals↗
PubMed2000

S(+)-ketamine up-regulates neuronal regeneration associated proteins following glutamate injury in cultured rat hippocampal neurons.

In previous studies, racemic ketamine improved neurological outcome after experimental brain injury and S(+)-ketamine demonstrated neuroprotective effects in neurons after damage in vitro. We compared the expression of regeneration-associated proteins in rat hippocampal neurons after glutamate injury and treatment with S(+)-ketamine versus racemic ketamine. Following an 8 minute exposure to 100 microM glutamate, neurons were maintained untreated or in the presence of S(+)-ketamine or racemic ketamine (10(-4) M, 10(-5) M, 10(-6) M) for one week. Growth-associated protein-43 (GAP-43) and synaptosomal-associated protein-25 (SNAP-25) was analyzed by Western Blotting, the mitochondrial transmembrane potential (MTP) by fluorescence imaging, and [3H]2-deoxy-D-glucose ([3H]2-DG) uptake by scintillation spectrometry. Seven days after exposure, GAP-43 decreased to 15% and SNAP-25 to 30% in the glutamate-injured, untreated neurons. The MTP declined to 50% and [3H]2-DG to 30%. Both S(+)-ketamine and racemic ketamine at 10(-4) M and 10(-5) M minimized the decline in MTP, almost maintaining it at control value. Additionally, S(+)-ketamine and racemic ketamine decreased the reduction in [3H]2-DG. S(+)-ketamine at 10(-4) M and 10(-5) M and racemic ketamine at 10(-4) M reduced the decline in SNAP-25 to 60% of controls (P < .05). However, S(+)-ketamine at 10(-4) M and 10(-5) M only reversed the decrease in GAP-43 to 50% and 40% of controls, respectively (P < .05). We conclude that the synthesis of a growth-associated protein related to plasticity and repair in the adult nervous system is increased by S(+)-ketamine but is not increased by racemic ketamine.

Animals↗
PubMed1999

Isoflurane induces dose-dependent changes of thalamic somatosensory information transfer.

In spite of several reports about suppressive effects of volatile anesthetics on somatosensation, their neuronal mechanisms are largely unknown. The present study investigates somatosensory impulse transmission at the thalamic level in rats under varied concentrations of isoflurane by recordings of neuronal responses to mechanical stimulation of the body surface. Single-unit recordings of thalamo-cortical relay neurons (TCNs, third order neurons; n=28) and presumed trigemino-thalamic fibers (TTFs, second order neurons; n=7) were performed in the ventral posteromedial nucleus. Functional response characteristics were quantified following defined tactile stimulation (trapezoidal or vibratory deflection of sinus hairs or fur) applied to the neuronal receptive fields. End-tidal isoflurane concentration was increased in steps of 0.2% between 0.6% (baseline) and 2.0%. The response activity in all TCNs studied was suppressed in a dose-dependent manner (2.0% isoflurane decreased responses to 3. 5+/-1.1% of baseline; mean+/-S.E.M.); the response activity in TTFs was much less affected (decrease to 55.0+/-8.2%). Suppression of ongoing activity, however, was similar for both, TCNs and TTFs. Furthermore, in TCNs, the response characteristics changed with increasing isoflurane between 1.0% and 1.8%: tonic and sustained responses were converted to phasic on-responses. In contrast, the tonic and sustained response characteristics of TTFs were preserved even at higher isoflurane concentrations. The results indicate that isoflurane attenuates the output of somatosensory signals in the specific nucleus of the rat's thalamus, while its input is only marginally affected. The observed changes of thalamic neuronal response characteristics, at least in part, may cause the loss in sensory discrimination observed during general anesthesia.

Anesthetics, Inhalation↗
PubMed1999

Cerebral blood flow velocity and carbon dioxide vasoreactivity during gamma-hydroxybutyrate/fentanyl anaesthesia in non-neurosurgical patients.

In this study the effects of gamma-hydroxybutyrate/fentanyl on cerebral blood flow velocity (CBFV) (as measured in the middle cerebral artery by transcranial Doppler ultrasonography) and on cerebrovascular carbon dioxide reactivity were investigated. Mean CBFV (Vmean) and haemodynamic responses were recorded in 12 non-neurosurgical patients before, during and after induction of general anaesthesia with gamma-hydroxybutyrate (GHB) (20 min constant rate infusion of 100 mg kg-1). Two patients were excluded, one because of bradycardia and the other because of severe myoclonia. During the infusion of GHB, normocapnia was maintained by manually assisting ventilation as necessary. The infusion of GHB did not affect Vmean [awake: 57 +/- 12 cm s-1 (mean +/- SD); 22.5 min: 62 +/- 15 cm s-1, NS difference] or mean arterial blood pressure (MAP) (awake: 97 +/- 12 mmHg; 22.5 min: 89 +/- 10 mmHg, NS). This suggests that cerebral blood flow velocity is unaltered by an anaesthetic dose of GHB. Twenty-five minutes after the start of GHB, fentanyl 3 micrograms kg-1 and vecuronium 0.1 mg kg-1 were given, the trachea was intubated and the lungs were mechanically ventilated to maintain end-tidal PCO2 of 4.6 +/- 0.4 kPa (30 min). At 30 min after the start of the GHB infusion, Vmean and MAP decreased to 38 +/- 10 cm s-1 and 76 +/- 12 mmHg (both P < 0.05 vs 22.5 min) respectively. After adjusting the ventilation to achieve hypocapnia (40 min: end-tidal PCO2 3.5 +/- 0.2 mmHg), Vmean decreased to 29 +/- 7 cm s-1, while MAP did not change. This allowed the relative vasoreactivity (percentage change in Vmean/0.133 kPa change in the end-tidal PCO2 from normocapnia to hypocapnia) to be estimated as 2.7 +/- 1.6% 0.133 kPa-1. This suggests that cerebrovascular response to CO2 during gamma-hydroxybutyrate/fentanyl anaesthesia is maintained.

Adolescent↗