Biomedical subjects

Peter Nagele

Publications and source records attributed to Peter Nagele.

5 recordsLinked to original sources

PubMed2005

Xenon acts by inhibition of non-N-methyl-D-aspartate receptor-mediated glutamatergic neurotransmission in Caenorhabditis elegans.

BACKGROUND: Electrophysiologic experiments in rodents have found that nitrous oxide and xenon inhibit N-methyl-D-aspartate (NMDA)-type glutamate receptors. These findings led to the hypothesis that xenon and nitrous oxide along with ketamine form a class of anesthetics with the identical mechanism, NMDA receptor antagonism. Here, the authors ask in Caenorhabditis elegans whether xenon, like nitrous oxide, acts by a NMDA receptor-mediated mechanism. METHODS: Xenon:oxygen mixtures were delivered into sealed chambers until the desired concentration was achieved. The effects of xenon on various behaviors were measured on wild-type and mutant C. elegans strains. RESULTS: With an EC50 of 15-20 vol% depending on behavioral endpoint, xenon altered C. elegans locomotion in a manner indistinguishable from that of mutants in glutamatergic transmission. Xenon reduced the frequency and duration of backward locomotion without altering its speed or other behaviors tested. Mutation of glr-1, encoding a non-NMDA glutamate receptor subunit, abolished the behavioral effects of xenon; however, mutation of nmr-1, which encodes the pore-forming subunit of an NMDA glutamate receptor previously shown to be required for nitrous oxide action, did not significantly alter xenon response. Transformation of the glr-1 mutant with the wild-type glr-1 gene partially restored xenon sensitivity, confirming that glr-1 was necessary for the full action of xenon. CONCLUSIONS: Xenon acts in C. elegans to alter locomotion through a mechanism requiring the non-NMDA glutamate receptor encoded by glr-1. Unlike for the action of nitrous oxide in C. elegans, the NMDA receptor encoded by nmr-1 is not essential for sensitivity to xenon.

Animals↗

PubMed2005

Volatile anesthetics bind rat synaptic snare proteins.

BACKGROUND: Volatile general anesthetics (VAs) have a number of synaptic actions, one of which is to inhibit excitatory neurotransmitter release; however, no presynaptic VA binding proteins have been identified. Genetic data in Caenorhabditis elegans have led to the hypothesis that a protein that interacts with the presynaptic protein syntaxin 1A is a VA target. Motivated by this hypothesis, the authors measured the ability of syntaxin 1A and proteins that interact with syntaxin to bind to halothane and isoflurane. METHODS: Recombinant rat syntaxin 1A, SNAP-25B, VAMP2, and the ternary SNARE complex that they form were tested. Binding of VAs to these proteins was detected by F-nuclear magnetic resonance relaxation measurements. Structural alterations in the proteins were examined by circular dichroism and ability to form complexes. RESULTS: Volatile anesthetics did not bind to VAMP2. At concentrations in the clinical range, VAs did bind to SNAP-25B; however, binding was detected only in preparations containing SNAP-25B homomultimers. VAs also bound at clinical concentrations to both syntaxin and the SNARE complex. Addition of an N-terminal His6 tag to syntaxin abolished its ability to bind VAs despite normal secondary structure and ability to form SNARE complexes; thrombin cleavage of the tag restored VA binding. Thus, the VA binding site(s) has structural requirements and is not simply any alpha-helical bundle. VAs at supraclinical concentrations produced an increase in helicity of the SNARE complex; otherwise, VA binding produced no gross alteration in the stability or secondary structure of the SNARE complex. CONCLUSION: SNARE proteins are potential synaptic targets of volatile anesthetics.

Anesthetics, Inhalation↗

PubMed2005

Over-the-head cardiopulmonary resuscitation improves efficacy in basic life support performed by professional medical personnel with a single rescuer: a simulation study.

Two-rescuer cardiopulmonary resuscitation (CPR) is considered the best method for professional basic life support (BLS). However, in many prehospital cardiac arrest situations, one rescuer has to begin CPR alone while the other performs additional tasks. In theory, over-the-head CPR is a suitable alternative in this situation, with the added benefit of allowing the single rescuer to use a self-inflating bag for ventilation. In this trial, we compared standard single-rescuer CPR with over-the-head CPR in manikins. We planned this study using a crossover study design where each participant administered both CPR techniques in a randomized order. Ventilation and chest compression data were collected with analysis software during a 2-min CPR test for each technique. Sixty-seven emergency medical technician students participated in this trial. Over-the-head CPR allowed for superior ventilation compared to standard CPR (number of correct ventilations: 330 of 760 versus 279 of 779; P = 0.002). The quality of delivered chest compressions did not differ between the two groups (correct chest compressions: 4293 of 6304 versus 4313 of 6395; P = 0.44). In conclusion, our study has shown that over-the-head CPR may be an effective alternative BLS technique when a single professional rescuer has to perform CPR, likely offering superior ventilation and comparable chest compression quality compared with standard BLS.

Adolescent↗

PubMed2004

Epidemiology and outcome of pediatric trauma treated by an emergency-physician-staffed advanced life-support unit.

BACKGROUND: The aim of this study was to describe the epidemiology and outcome of pediatric trauma in the setting of an emergency-physician-staffed mobile advanced life support (ALS) unit serving a predominantly urban area in Austria. METHODS: In this retrospective chart review, all pediatric trauma patients (0-14 years of age) who were treated by a physician-staffed ALS unit in Innsbruck within a 3-year period were analyzed. In addition, hospital charts were assessed to determine the clinical course and the outcome of these patients. RESULTS: 113 injured children were treated by the physician-staffed ALS unit (1.5% of all runs) during the study period; a frequency of three pediatric trauma patients per month. On average, injuries were of moderate severity (2.6 +/- 1.3 on the NACA severity scale). Thirteen children (11.5%) sustained severe to life-threatening injuries and two of whom underwent out-of-hospital resuscitation. The majority of the injuries were caused by vehicular accidents and sports/recreation-related trauma; head trauma was the most frequent injury. Violence-related trauma including weapon-inflicted injuries was uncommon. 40% of the children were hospitalized. The overall outcome was favorable: 78% of the hospitalized children had no impairment at the time of discharge. By comparing the prehospital trauma diagnosis with the final diagnosis, we found that the vast majority of emergency-physician trauma diagnoses were accurate. CONCLUSION: Because the frequency of pediatric trauma is so low, ALS units may not gain adequate experience in the management of (severe) pediatric trauma, thus rendering regular training of paramount importance.

Adolescent↗

PubMed2003

Multicenter randomized comparison of the efficacy and safety of xenon and isoflurane in patients undergoing elective surgery.

BACKGROUND: All general anesthetics used are known to have a negative inotropic side effect. Since xenon does not have a negative inotropic effect, it could be an interesting future general anesthetic. The aim of this clinical multicenter trial was to test the hypothesis of whether recovery after xenon anesthesia is faster compared with an accepted, standardized anesthetic regimen and that it is as effective and safe. METHOD: A total of 224 patients in six centers were included in the protocol. They were randomly assigned to receive either xenon (60 +/- 5%) in oxygen or isoflurane (end-tidal concentration, 0.5%) combined with nitrous oxide (60 +/- 5%). Sufentanil (10 mcirog) was intravenously injected if indicated by defined criteria. Hemodynamic, respiratory, and recovery parameters, the amount of sufentanil, and side effects were assessed. RESULTS: The recovery parameters demonstrated a statistically significant faster recovery from xenon anesthesia when compared with isoflurane-nitrous oxide. The additional amount of sufentanil did not differ between both anesthesia regimens. Hemodynamics and respiratory parameters remained stable throughout administration of both anesthesia regimens, with advantages for the xenon group. Side effects occurred to the same extent with xenon in oxygen and isoflurane-nitrous oxide. CONCLUSION: This first randomized controlled multicenter trial on the use of xenon as an inhalational anesthetic confirms, in a large group of patients, that xenon in oxygen provides effective and safe anesthesia, with the advantage of a more rapid recovery when compared with anesthesia using isoflurane-nitrous oxide.

Adjuvants, Anesthesia↗