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1.
Neurol Res Pract ; 5(1): 13, 2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37020243

RESUMEN

BACKGROUND: Infective endocarditis (IE) is a serious condition with a high mortality, represents a rare cause of stroke and an increased risk of intracranial hemorrhage. In this single center study, we characterize stroke patients with IE. We were interested in risk factors for intracranial hemorrhage and outcome of patients with intracranial hemorrhage compared to patients with ischemic stroke. METHODS: Patients with IE and symptomatic ischemic stroke or intracranial hemorrhage admitted to our hospital between January 2019 and December 2022 were included in this retrospective study. RESULTS: 48 patients with IE and ischemic stroke or intracranial hemorrhage were identified. 37 patients were diagnosed with ischemic stroke, 11 patients were diagnosed with intracranial hemorrhage. The intracranial hemorrhage occurred within the first 12 days after admission. We identified Staphylococcus aureus detection and thrombocytopenia as risk factors for hemorrhagic complications. An increased in-hospital mortality in patients with intracranial hemorrhage (63.6% vs. 22%, p = 0.022) was found, whereas patients with ischemic stroke and patients with intracranial hemorrhage do not differ regarding favorable clinical outcome (27% vs. 27.3%, p = 1.0). 27.3% patients with intracranial hemorrhage and 43.2% patients with ischemic stroke underwent cardiac surgery. Overall, 15.7% new ischemic strokes occurred after valve reconstruction, whereas no new intracranial hemorrhage was observed. CONCLUSIONS: We found an increased in-hospital mortality in patients with intracranial hemorrhage. Beside thrombocytopenia, we identified S. aureus detection as a risk factor for intracranial hemorrhage.

2.
BJS Open ; 5(2)2021 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-33688947

RESUMEN

BACKGROUND: Antimicrobial prophylaxis (AMP) adjustment according to bodyweight to prevent surgical-site infections (SSI) is controversial. The impact of weight-adjusted AMP dosing on SSI rates was investigated here. METHODS: Results from a first study of patients undergoing visceral, vascular or trauma operations, and receiving standard AMP, enabled retrospective evaluation of the impact of bodyweight and BMI on SSI rates, and identification of patients eligible for weight-adjusted AMP. In a subsequent observational prospective study, patients weighing at least 80 kg were assigned to receive double-dose AMP. Risk factors for SSI, including ASA classification, duration and type of surgery, wound class, diabetes, weight in kilograms, BMI, age, and AMP dose, were evaluated in multivariable analysis. RESULTS: In the first study (3508 patients), bodyweight and BMI significantly correlated with higher rates of all SSI subclasses (both P < 0.001). An 80-kg cut-off identified patients receiving single-dose AMP who were at higher risk of SSI. In the prospective study (2161 patients), 546 patients weighing 80 kg or more who received only single-dose AMP had higher rates of all SSI types than a group of 1615 who received double-dose AMP (odds ratio (OR) 4.40, 95 per cent c.i. 3.18 to 6.23; P < 0.001). In multivariable analysis including 5021 patients from both cohorts, bodyweight (OR 1.01, 1.00 to 1.02; P = 0.008), BMI (OR 1.01, 1.00 to 1.02; P = 0.007) and double-dose AMP (OR 0.33, 0.23 to 0.46; P < 0.001) among other variables were independently associated with SSI rates. CONCLUSION: Double-dose AMP decreases SSI rates in patients weighing 80 kg or more.


Asunto(s)
Antibacterianos/administración & dosificación , Profilaxis Antibiótica/métodos , Peso Corporal , Infección de la Herida Quirúrgica/prevención & control , Adulto , Anciano , Índice de Masa Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo
4.
Anaesthesist ; 59(10): 914-7, 2010 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-20827453

RESUMEN

Maple syrup urine disease is a rare autosomal-recessive metabolic disorder caused by a deficit of oxidative decarboxylation of branched-chain amino acids. First symptoms appear in the neonatal period. Without treatment the disease is characterized by rapid progression of neurological symptoms. During stressful situations, such as infection or surgery, patients may experience severe ketoacidosis, rapid neurological deterioration and hypoglycemia. The perioperative management of a 26-year-old man with maple syrup urine disease is described, a review of the disease is given and anaesthesia-related implications are discussed.


Asunto(s)
Anestesia , Enfermedad de la Orina de Jarabe de Arce/terapia , Adulto , Humanos , Hipoglucemia/etiología , Leucina , Masculino , Enfermedad de la Orina de Jarabe de Arce/complicaciones , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/psicología , Atención Perioperativa
5.
J Bone Joint Surg Br ; 87(8): 1134-9, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16049253

RESUMEN

Using a computer-based quality assurance program, we analysed peri-operative data on 160 patients undergoing one-stage bilateral hip or knee arthroplasties under regional anaesthesia with routine anaesthetic monitoring and only using peripheral intravenous access for peri-operative safety. We monitored defined intra-operative adverse events such as hypotension, myocardial ischaemia, arrhythmias, hypovolaemia, hypertension and early post-operative complications. We also determined post-operative hip and knee function, and patient satisfaction with different aspects of the anaesthetic management. Those patients undergoing one-stage bilateral arthroplasties were matched according to a cross-stratification which used three variables (American Society of Anesthesiologists' physical status scoring system, age and joint replaced) to patients undergoing unilateral hip or knee arthroplasties. Serious intra-operative adverse events were, with the exception of intra-operative hypotension, very infrequent in patients undergoing bilateral (nine adverse events) as well as unilateral arthroplasties (five adverse events). Early post-operative complications were also infrequent in both groups. However, the risks of receiving a heterologous blood transfusion (odds ratio 2.5; 95% confidence interval (CI) 1.3 to 5.0, estimated by exact conditional logistic regression) or vasoactive drugs (odds ratio 3.9; 95% CI 2.0 to 7.8) were significantly greater for patients undergoing bilateral operations. Patient satisfaction with anaesthesia was high; all patients who underwent the one-stage bilateral operation would choose the same anaesthetic technique again.


Asunto(s)
Anestesia de Conducción/métodos , Artroplastia de Reemplazo de Cadera/métodos , Artroplastia de Reemplazo de Rodilla/métodos , Monitoreo Intraoperatorio/métodos , Anciano , Anciano de 80 o más Años , Transfusión Sanguínea , Estudios de Casos y Controles , Femenino , Costos de Hospital , Humanos , Complicaciones Intraoperatorias , Tiempo de Internación , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Suiza , Vasoconstrictores/administración & dosificación
6.
Anaesthesist ; 54(11): 1094-9, 2005 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-16001269

RESUMEN

BACKGROUND: In the last 20 years molecular biology has expanded the horizons of medical research including anaesthesia. Preoperative identification of genetic disorders relevant to anaesthesia or increased perioperative risk will be available in the near future using molecular biology techniques. There has been a global increase of such publications, but the contributions from Germany, Switzerland and Austria are unknown. MATERIAL AND METHODS: An internet-based medline search was used to analyse specific features such as year of publication, journal and origin of molecular biology articles produced by German, Swiss and Austrian anaesthesia institutions from 1988 to 2002. RESULTS: During the study period 121 articles from German institutions were published, 18 from Switzerland and 5 from Austria, corresponding to 10%, 1.5% and 0.4%, respectively, of global publications. In Germany the number of anaesthesia publications with a molecular biology content has continuously increased, but in Switzerland and Austria the numbers have remained constant. The majority of articles were published in high-impact non-anaesthesia journals. DISCUSSION AND CONCLUSION: The results of this study show the quantitative development of molecular biology research that has been done in anaesthesia institutions in Germany, Switzerland and Austria from 1988 to 2002. A continuous increase of publications with a molecular biology content occurred only in Germany.


Asunto(s)
Anestesiología/estadística & datos numéricos , Bibliometría , Biología Molecular/estadística & datos numéricos , Austria , Alemania , Publicaciones Periódicas como Asunto , Edición , Investigación , Suiza
7.
Anaesthesia ; 60(1): 53-9, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15601273

RESUMEN

Previous communication research in general medical practice has shown that effective communication enhances patient compliance, satisfaction and medical outcome. It is expected that communication is equally important in anaesthesia, since patients often suffer from anxiety and lack of knowledge about anaesthetic procedures. However, little is known about the nature of communication during routine anaesthetic visits. The present study of 57 authentic anaesthetic visits provides the first results on the structure and content of communication in the pre-operative setting using the Roter Interaction Analysis System (RIAS). Patient-centred communication behaviours of anaesthetists and the extent of patient involvement were particularly investigated. From the 57 pre-operative visits, 18 267 utterances were coded. The mean (SD) [range] duration of the visit was 16.1 (7.8) [3.7-42.7] min. Anaesthetists provided 169 (68) and patients 153 (82) utterances per visit (53.5% vs. 46.5%). Physician and patient gender had no impact on the distribution of utterances and the duration of the visit. Conversation mainly focussed on biomedical issues with little psychosocial discussion (< 0.1% of all anaesthetist utterances). However, anaesthetists quite frequently used emotional comments toward patients (7%) and involved them in the conversation. The use of facilitators, open questions and emotional statements by the anaesthetist correlated with high patient involvement. The amount of patient participation in anaesthetic decisions was assessed with the Observing Patient Involvement Scale (OPTION). Compared with general practitioners, anaesthetists offered more opportunities to discuss treatment options (mean (SD) OPTION score 26.8 (16.8) vs. 16.8 (7.7)).


Asunto(s)
Anestesiología/normas , Comunicación , Relaciones Médico-Paciente , Cuidados Preoperatorios/normas , Adulto , Femenino , Humanos , Masculino , Educación del Paciente como Asunto/normas , Participación del Paciente , Psicometría , Suiza , Grabación de Cinta de Video
8.
Anaesthesist ; 54(1): 29-34, 2005 Jan.
Artículo en Alemán | MEDLINE | ID: mdl-15551106

RESUMEN

Shone's anomaly was first described in 1963 as a developmental complex of four potentially obstructive cardiac lesions including a supravalvular fibrous mitral ring, deformity of the mitral and/or subvalvular apparatus, subvalvular aortic stenosis and coarctation of the aorta. While paediatric patients with Shone's anomaly have been reported in the literature, only a few adult patients presenting with this anomaly have been described in the perioperative period. However, patients with an undiagnosed, incomplete form of Shone's anomaly might occasionally present for non-cardiac surgery as adults. In this case report we describe the anaesthetic management of an adult patient scheduled for a non-cardiac operation, who suffered from Shone's anomaly that was unrecognised prior to the operation.


Asunto(s)
Anestesia , Coartación Aórtica/patología , Estenosis Aórtica Subvalvular/patología , Enfermedades de las Válvulas Cardíacas/patología , Estenosis de la Válvula Mitral/patología , Coartación Aórtica/diagnóstico por imagen , Estenosis Aórtica Subvalvular/diagnóstico por imagen , Femenino , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Hemodinámica/fisiología , Humanos , Histerectomía , Persona de Mediana Edad , Estenosis de la Válvula Mitral/diagnóstico por imagen , Síndrome , Ultrasonografía
9.
Anaesthesia ; 59(10): 1002-7, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15488060

RESUMEN

Molecular biology has expanded the horizons of anaesthesia during the last 20 years and has led to an increase of basic science articles that are published in the specialised anaesthetic journals or originate in anaesthetic institutions. We searched for and analysed the specific features, such as year of publication, publishing journal, and country of origin, of all such molecular biology articles stored in the MEDLINE database during the period 1986-2002. We identified 1265 original articles that used molecular biology techniques; 223 (18%) of these articles were published in anaesthetic journals and 1042 (82%) articles in 556 other biomedical journals. While in the late 1980s only a few molecular biology articles were published each year by anaesthetic institutions, worldwide this number reached approximately 200 basic science articles by the end of 2002. The USA clearly dominates the field of anaesthesia with respect to molecular biology research with 839 (66%) such articles.


Asunto(s)
Anestesia/estadística & datos numéricos , Bibliometría , Biología Molecular/estadística & datos numéricos , Investigación Biomédica/métodos , Investigación Biomédica/estadística & datos numéricos , Humanos , Publicaciones Periódicas como Asunto/estadística & datos numéricos , Edición/estadística & datos numéricos
11.
Anaesthesia ; 59(2): 166-72, 2004 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-14725519

RESUMEN

The attitude, behaviour and communication skills of specialised doctors are increasingly recognised as important and they have been identified as training requirements. We designed a programme to teach communication skills to doctors in a University Department of Anaesthesia and evaluated its effect on patient outcomes such as satisfaction and anxiety. The 20 h programme was based on videotaped reviews of actual pre-operative visits and role-playing. Effects on patient satisfaction and pre-operative anxiety were assessed using a patient questionnaire. In addition, all participating anaesthetists assessed the training. We provide evidence that the training increased patient satisfaction with the pre-operative anaesthetic visit. Training also decreased anxiety associated with specific aspects of anaesthesia and surgery, but the effect was rather small given the intense programme. The anaesthetists agreed that their interpersonal skills increased and they felt better prepared to understand patients' anxieties. Communication skills training can increase patient satisfaction and decrease specific anxieties. The authors conclude that in order to better demonstrate the efficacy of such a training programme, the particular communication skills of anaesthetists rather than indirect patient outcome parameters should be measured.


Asunto(s)
Anestesiología/educación , Comunicación , Educación Médica Continua/métodos , Relaciones Médico-Paciente , Adulto , Anciano , Ansiedad/prevención & control , Actitud del Personal de Salud , Competencia Clínica , Femenino , Humanos , Masculino , Cuerpo Médico de Hospitales/educación , Cuerpo Médico de Hospitales/psicología , Persona de Mediana Edad , Modelos Estadísticos , Satisfacción del Paciente , Suiza
12.
Anaesthesist ; 51(11): 890-6, 2002 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-12434262

RESUMEN

OBJECTIVES: The role or recognition of the anaesthetist as an independent medical specialist has been the subject of many studies. Since most of this work was performed in English speaking countries, only few data are available for Germany, Austria, or Switzerland. The goal of this study was to determine how much knowledge patients had of the training and activities of anaesthetists. The study included patients ( n=685) who underwent elective operations in all surgical subspecialties at the University Hospital of Basel. METHODS: The data were collected using a questionnaire distributed at the end of the preoperative visit, which included 14 different questions examining the role of the anaesthetist. RESULTS: Surprisingly, and in contrast to previous studies, almost all patients (99%) knew that the anaesthetist is a qualified physician. In addition, 75% of the patients were aware that the anaesthetist is also engaged in activities outside the operating room; these percentages compare favourably with previous results. However, when asked about the specifics of these activities or about how long it takes to train an anaesthetist, the Swiss patients knew little more than patients from other countries. Only one fifth of all patients estimated the duration of postgraduate training correctly and 45% thought that the anaesthesia team worked under the supervision of the surgical team. Previous anaesthetic experiences as well as additional informational material such as a booklet or videofilm did not improve the patients' knowledge with respect to the training or activities of anaesthetists. DISCUSSION: Since other even more elaborate and expensive methods such as large exhibitions, national anaesthesia days, or increased coverage on radio and television also failed to enhance patients' knowledge, the focus is once again on the relationship between the patient and anaesthetist. If we wish to improve the role and recognition of anaesthetists for patients and/or the public, the anaesthetist must be visible for the patients as a true physician in the pre- and postoperative period. To improve this important patient-anaesthetist relationship, we have begun a training program in communication skills for all physicians in our department.


Asunto(s)
Anestesia , Relaciones Profesional-Paciente , Recolección de Datos , Femenino , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales , Encuestas y Cuestionarios , Suiza
13.
Brain Res Mol Brain Res ; 80(1): 99-108, 2000 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-11039733

RESUMEN

Recently, a new family of potassium channels with two pore domains in tandem and four transmembrane segments has been identified. Seven functional mammalian channels have been reported at this time. These channels give rise to baseline potassium currents because they are not gated by voltage and exhibit spontaneous activity at all membrane potentials. Although the physiological role of these ion channels has yet to be determined, three mammalian members of this family (TREK-1, TASK-1, TASK-2) are activated by volatile anesthetics and may therefore contribute to the central nervous system (CNS) depression produced by volatile anesthetics. In this study we used northern blot analysis and immunohistochemical localization to determine the expression of TASK-1 subunits in the CNS. TASK-1 immunoreactivity was prominently found in astrocytes of the hippocampus, in the median eminence, in the choroid plexus, and the granular layer, Purkinje cell layer, and molecular layer of the cerebellum. In the spinal cord, strong TASK-I immunoreactivity was seen in ependymal cells lining the central canal and in white matter. These findings suggest a role for the TASK-1 channel in the production of cerebrospinal fluid and function of hypothalamic neurosecretory cells.


Asunto(s)
Sistema Nervioso Central/química , Proteínas del Tejido Nervioso/análisis , Canales de Potasio de Dominio Poro en Tándem , Canales de Potasio/análisis , Secuencia de Aminoácidos , Animales , Electroforesis en Gel de Poliacrilamida , Inmunohistoquímica , Masculino , Ratones , Microscopía Fluorescente , Datos de Secuencia Molecular , Ratas , Ratas Sprague-Dawley
14.
Anesthesiology ; 92(6): 1722-30, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10839924

RESUMEN

BACKGROUND: Previous studies have identified a volatile anesthetic-induced increase in baseline potassium permeability and concomitant neuronal inhibition. The emerging family of tandem pore domain potassium channels seems to function as baseline potassium channels in vivo. Therefore, we studied the effects of clinically used volatile anesthetics on a recently described member of this family. METHODS: A cDNA clone containing the coding sequence of KCNK5 was isolated from a human brain library. Expression of KCNK5 in the central nervous system was determined by Northern blot analysis and reverse-transcription polymerase chain reaction. Functional expression of the channel was achieved by injection of cRNA into Xenopus laevis oocytes. RESULTS: Expression of KCNK5 was detected in cerebral cortex, medulla, and spinal cord. When heterologously expressed in Xenopus oocytes, KCNK5 currents exhibited delayed activation, outward rectification, proton sensitivity, and modulation by protein kinase C. Clinical concentrations of volatile general anesthetics potentiated KCNK5 currents by 8-30%. CONCLUSION: Human KCNK5 is a tandem pore domain potassium channel exhibiting delayed activation and sensitivity to volatile anesthetics and may therefore have a role in suppressing cellular excitability during general anesthesia.


Asunto(s)
Anestésicos por Inhalación/farmacología , Canales de Potasio de Dominio Poro en Tándem , Canales de Potasio/agonistas , Animales , Northern Blotting , Clonación Molecular , Humanos , Técnicas In Vitro , Masculino , Potenciales de la Membrana/efectos de los fármacos , Mutagénesis Sitio-Dirigida , Oocitos/metabolismo , Oocitos/fisiología , Técnicas de Placa-Clamp , Sistema Nervioso Periférico , Canales de Potasio/genética , Canales de Potasio/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Médula Espinal/metabolismo , Distribución Tisular , Xenopus laevis
15.
Anesth Analg ; 90(3): 706-12, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10702461

RESUMEN

UNLABELLED: The advent of managed care, reduction of costs, and advances in medical technology place increasing demands on anesthesiologists. Preoperative anxiety may go unnoticed in an environment that stresses increased productivity. The present study compares different methods for measuring preoperative anxiety, identifies certain patient characteristics that predispose to high anxiety, and describes the quantity and quality of anxiety that patients experience preoperatively. Seven hundred thirty-four patients participated in the study. We assessed aspects of anxiety by means of visual analog scales (VAS) and the State Anxiety Score of the Spielberger State-Trait Anxiety Inventory (STAI). The mean STAI anxiety score was 39 +/- 1 (n = 486) and the mean VAS for fear of anesthesia was 29 +/- 1 (n = 539). Patients feared surgery significantly more than anesthesia (P < 0.001). The VAS measuring fear of anesthesia correlated well with the STAI score (r = 0.55; P < 0.01). Young patients, female patients, and patients with no previous anesthetic experience or a previous negative anesthetic experience had higher anxiety scores. Patients worried most about the waiting period preceding surgery and were least concerned about possible awareness intraoperatively. Factor analysis of various anxiety items showed three distinct dimensions of fear: 1) the fear of the unknown 2) the fear of feeling ill, and 3) the fear for one's life. Among these dimensions, fear of the unknown correlated highest with the anxiety measuring techniques STAI and VAS. The simple VAS proved to be a useful and valid measure of preoperative anxiety. IMPLICATIONS: The study of qualitative aspects of anxiety reveals three distinct dimensions of preoperative fear: fear of the unknown, fear of feeling ill, and fear for one's life. Groups of patients with a higher degree of preoperative anxiety and their specific anesthetic concerns can be identified using the visual analog scale.


Asunto(s)
Anestesia , Ansiedad/diagnóstico , Procedimientos Quirúrgicos Operativos/psicología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Psicológicas
16.
Anesthesiology ; 92(3): 821-32, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10719961

RESUMEN

BACKGROUND: Neuromuscular disorders associated with muscular weakness and prolonged paralysis are common in critically ill patients. Acute myopathy has been described in patients receiving a combination therapy of corticosteroids and nondepolarizing neuromuscular blocking drugs for treatment of acute bronchospasm. The cause of this myopathy is not fully established and may involve drug interactions that perturb neuromuscular transmission. To investigate the interaction of corticosteroids with neuromuscular blocking drugs, the authors determined the effects of methylprednisolone and hydrocortisone alone and in combination with vecuronium on fetal (gamma-subunit containing) and adult (epsilon-subunit containing) subtypes of the muscle-type nicotinic acetylcholine receptor. METHODS: Functional channels were expressed in Xenopus laevis oocytes and activated with 1 microM acetylcholine. The resulting currents were recorded using a whole cell two-electrode voltage clamp technique. RESULTS: Both forms of the muscle-type acetylcholine receptor were potently inhibited by methylprednisolone and hydrocortisone, with concentrations producing 50% inhibition in the range of 400-600 microM and 1-2 mM, respectively. The corticosteroids produced noncompetitive antagonism of the muscle-type nicotinic acetylcholine receptor at clinical concentrations. Both receptor forms were also inhibited, even more potently, by vecuronium, with a concentration producing 50% inhibition in the range of 1-2 nM. Combined application of vecuronium and methylprednisolone showed additive effects on both receptor forms, which were best described by a two-site model, with each site independent. CONCLUSIONS: The enhanced neuromuscular blockade produced when corticosteroids are combined with vecuronium may augment pharmacologic denervation and contribute to the pathophysiology of prolonged weakness observed in some critically ill patients.


Asunto(s)
Corticoesteroides/farmacología , Fármacos Neuromusculares no Despolarizantes/farmacología , Receptores Nicotínicos/efectos de los fármacos , Bromuro de Vecuronio/farmacología , Algoritmos , Animales , Sinergismo Farmacológico , Glucocorticoides/farmacología , Humanos , Hidrocortisona/farmacología , Metilprednisolona/farmacología , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Técnicas de Placa-Clamp , Xenopus
18.
Anesth Analg ; 88(5): 1168-74, 1999 May.
Artículo en Inglés | MEDLINE | ID: mdl-10320189

RESUMEN

UNLABELLED: Anesthetics cause a reduction in excitatory neurotransmission that may be important in the mechanisms of in vivo anesthetic action. Because glutamate is the major excitatory neurotransmitter in mammalian brain, evaluation of anesthetic effects on induced glutamate release is relevant for studying this potential mechanism of anesthetic action. In the present study, we compared the effects of anesthetics and nonanesthetics (halogenated alkanes that disobey the Meyer-Overton hypothesis) on depolarization-evoked glutamate release. Glutamate released from rat cortical brain slices after chemically induced depolarization (50 mM KCl) was measured continuously using an enzymatic fluorescence assay. The effects of the volatile anesthetics isoflurane and enflurane were compared with the effects of the transitional compound 1,1,2-trichlorotrifluoroethane, the nonanesthetic compound 1,2-dichlorohexafluorocyclobutane, and other polyhalogenated alkanes. Tested concentrations included effective anesthetic concentrations for the anesthetics and transitional compounds, and concentrations predicted to be anesthetic based on lipid solubility for the nonanesthetics. Isoflurane dose-dependently reduced depolarization-evoked glutamate release in cortical brain slices. Isoflurane and enflurane at concentrations equivalent to 1 minimum alveolar anesthetic concentration (MAC) reduced the KCl-evoked release to 20% and 17% of control, respectively. The transitional compound 1,1,2-trichlorotrifluoroethane at 210 microM (approximately 1.2 MAC) reduced glutamate release to 47%, and the nonanesthetic 1,2-dichlorohexafluorocyclobutane increased glutamate release at 70 microM (approximately 3 MAC). These findings support the hypothesis that the modulation of excitatory neurotransmission might be responsible, in part, for in vivo anesthetic action. IMPLICATIONS: The volatile anesthetics isoflurane and enflurane reduce depolarization-evoked glutamate release in rat brain slices. The transitional compound 1,1,2-trichlorotrifluoroethane reduces glutamate release to a much lesser extent, and the nonanesthetic 1,2-dichlorohexafluorocyclobutane does not reduce glutamate release. These findings support the hypothesis that the modulation of excitatory neurotransmission might be responsible, in part, for in vivo anesthetic action.


Asunto(s)
Alcanos/farmacología , Anestésicos por Inhalación/farmacología , Corteza Cerebral/efectos de los fármacos , Ácido Glutámico/metabolismo , Animales , Corteza Cerebral/metabolismo , Relación Dosis-Respuesta a Droga , Potenciales de la Membrana , Cloruro de Potasio/farmacología , Ratas , Ratas Sprague-Dawley
19.
Anesthesiology ; 90(4): 1092-102, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10201682

RESUMEN

BACKGROUND: Recently, a new structural family of potassium channels characterized by two pore domains in tandem within their primary amino acid sequence was identified. These tandem pore domain potassium channels are not gated by voltage and appear to be involved in the control of baseline membrane conductances. The goal of this study was to identify mechanisms of local anesthetic action on these channels. METHODS: Oocytes of Xenopus laevis were injected with cRNA from five cloned tandem pore domain baseline potassium channels (TASK, TREK-1, TOK1, ORK1, and TWIK-1), and the effects of several local anesthetics on the heterologously expressed channels were assayed using two-electrode voltage-clamp and current-clamp techniques. RESULTS: Bupivacaine (1 mM) inhibited all studied tandem pore potassium channels, with TASK inhibited most potently. The potency of inhibition was directly correlated with the octanol: buffer distribution coefficient of the local anesthetic, with the exception of tetracaine, to which TASK is relatively insensitive. The approximate 50% inhibitory concentrations of TASK were 709 microM mepivacaine, 222 microM lidocaine, 51 microM R(+)-ropivacaine, 53 microM S(-)-ropivacaine, 668 microM tetracaine, 41 microM bupivacaine, and 39 microM etidocaine. Local anesthetics (1 mM) significantly depolarized the resting membrane potential of TASK cRNA-injected oocytes compared with saline-injected control oocytes (tetracaine 22+/-6 mV rs. 7+/-1 mV, respectively, and bupivacaine 31+/-7 mV vs. 6+/-4 mV). CONCLUSIONS: Local anesthetics inhibit tandem pore domain baseline potassium channels, and they could depolarize the resting membrane potential of cells expressing these channels. Whether inhibition of these channels contributes to conduction blockade or to the adverse effects of local anesthetics remains to be determined.


Asunto(s)
Anestésicos Locales/farmacología , Bloqueadores de los Canales de Potasio , Animales , Bupivacaína/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Concentración de Iones de Hidrógeno , Potenciales de la Membrana/efectos de los fármacos , Canales de Potasio/fisiología , Estereoisomerismo , Xenopus laevis
20.
Anesthesiology ; 90(4): 1137-45, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10201687

RESUMEN

BACKGROUND: An increase in intracellular calcium concentration ([Ca2+]i) in neurons has been proposed as an important effect of volatile anesthetics, because they alter signaling pathways that influence neurotransmission. However, the existing data for anesthetic-induced increases in [Ca2+]i conflict. METHODS: Changes in [Ca2+]i were measured using fura-2 fluorescence spectroscopy in rat cortical brain slices at 90, 185, 370, and 705 microM isoflurane. To define the causes of an increase in [Ca2+]i, slices were studied in Ca2+-free medium, in the presence of Ca2+-channel blockers, and in the presence of the Ca2+-release inhibitor azumolene. The authors compared the effect of the volatile anesthetic with that of the nonanesthetic compound 1,2-dichlorohexafluorocyclobutane. Single-dose experiments in CA1 neurons in hippocampal slices with halothane (360 microM) and in acutely dissociated CA1 neurons with halothane (360 microM) and isoflurane (445 microM) also were performed. RESULTS: Isoflurane at 0.5, 1, and 2 minimum alveolar concentrations increased basal [Ca2+]i in cortical slices in a dose-dependent manner (P < 0.05). This increase was not altered by Ca2+-channel blockers or Ca2+-free medium but was reduced 85% by azumolene. The nonanesthetic 1,2-dichlorohexafluorocyclobutane did not increase [Ca2+]i. In dissociated CA1 neurons, isoflurane reversibly increased basal [Ca2+]i by 15 nM (P < 0.05). Halothane increased [Ca2+]i in dissociated CA1 neurons and CA1 neurons in hippocampal slices by approximately 30 nM (P < 0.05). CONCLUSIONS: (1) Isoflurane and halothane reversibly increase [Ca2+]i in isolated neurons and in neurons within brain slices. (2) The increase in [Ca2+]i is caused primarily by release from intracellular stores. (3) Increases in [Ca2+]i occur with anesthetics but not with the nonanesthetic 1,2-dichlorohexafluorocyclobutane.


Asunto(s)
Anestésicos por Inhalación/farmacología , Calcio/metabolismo , Corteza Cerebral/efectos de los fármacos , Halotano/farmacología , Hipocampo/efectos de los fármacos , Isoflurano/farmacología , Animales , Corteza Cerebral/metabolismo , Hipocampo/metabolismo , Ratas , Ratas Sprague-Dawley
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