RESUMEN
Alcohols, inhaled anesthetics, and some injectable anesthetics inhibit the function of N-methyl-d-aspartate (NMDA) receptors, but the mechanisms responsible for this inhibition are not fully understood. Recently, it was shown that ethanol inhibition of NMDA receptors was reduced by mutation of residues in the transmembrane (TM) segment 3 of the NR1 subunit (F639A) or in TM4 of the NR2A subunit (A825W), suggesting putative ethanol binding sites. We hypothesized that the actions of other anesthetics might also require these amino acids and evaluated the effects of anesthetics on the NMDA receptors expressed in Xenopus oocytes with two-electrode voltage-clamp recording. Effects of hexanol, octanol, isoflurane, halothane, chloroform, cyclopropane, 1-chloro-1,2,2-trifluorocyclobutane, and xenon were reduced or eliminated in the mutant NMDA receptors, whereas the inhibitory effects of nitrous oxide, ketamine, and benzene were not affected by these mutations. Rapid applications of glutamate and glycine by a T-tube device provided activation time constants, which suggested different properties of ketamine and isoflurane inhibition. Thus, amino acids in TM3 and TM4 are important for the actions of many anesthetics, but nitrous oxide, benzene, and ketamine seem to have distinct mechanisms for inhibition of the NMDA receptors.
Asunto(s)
Anestésicos/farmacología , Mutación , Oocitos/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/biosíntesis , Receptores de N-Metil-D-Aspartato/genética , Sustitución de Aminoácidos/genética , Anestésicos por Inhalación/farmacología , Anestésicos Intravenosos/farmacología , Animales , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Oocitos/metabolismo , Xenopus laevisRESUMEN
PURPOSE: Delay in discharge after ambulatory surgery impairs its cost-effectiveness. However, it is not self-evident that prolonged postoperative stay is associated with low quality of care and patient acceptability of ambulatory surgery. The aims of this study were to document factors affecting delay in discharge, recovery profiles, and patient acceptability in adult outpatients. METHODS: Perioperative data were collected prospectively on consecutive 726 adult same-day surgical patients receiving general anesthesia. Factors that affected home-readiness, discharge, and unanticipated admission were noted. Patients were followed up 24 h after discharge using a standardized questionnaire to identify postdischarge symptoms, patient's self-rated resumption of normal activity (RNA) level, and preference of outpatient procedure. RESULTS: Eighty-two percent of patients were discharged home <270 min after operation, 16% were delayed (> or = 270 min), and 2% required unanticipated admission. Delayed patients reported postdischarge pain more frequently (53%) and a lower 24-h postoperative RNA level (7.2 +/- 1.8) and preference ratio (76%) than no-delay patients (34%, 8.0 +/- 1.9, 87%, respectively; P < 0.001). Delay in home-readiness (> or = 165 min) was mainly due to an adverse symptom, and delay in discharge after reaching home-readiness (> or = 150 min) was mainly due to a persistent symptom (58%) or a social/system problem (34%). Causes of admission were perioperative complications (80%) or social reasons (20%). CONCLUSION: Delays in discharge are mainly due to adverse symptoms or social/system problems. Delayed discharge is associated with increased postdischarge pain, lower RNA level, and patient acceptability. Appropriate care of postoperative symptoms and system management could prevent delay in discharge and improve patient RNA level and acceptability.
Asunto(s)
Procedimientos Quirúrgicos Ambulatorios , Anestesia General , Aceptación de la Atención de Salud , Alta del Paciente , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Factores de TiempoRESUMEN
PURPOSE: Leukocyte recruitment from blood vessels to inflamed tissues is the central step in the process of inflammation. This may cause damage of the inflamed tissues in the case of severe inflammatory conditions such as ischemia reperfusion or graft rejection. Adhesion molecules, such as E-selectin, are induced on activated endothelium and play an important role in this process. Volatile anesthetics protect tissues or organs in such conditions, and inhibition of leukocyte adhesion by anesthetics has been implicated. However, little is known about how the anesthetics act on individual adhesion molecules. We examined the effects of volatile anesthetics on E-selectin mediated leukocyte adhesion in a static condition using HL-60 cells, a granulocyte cell line, and E-selectin-coated plates as well as cytokine-activated human umbilical vein endothelial cells (HUVEC). METHODS: The adhesion assay was carried out by overlaying fluorescence-labeled HL-60 cells on E-selectin-coated plates or cytokine-activated HUVEC. E-selectin in the coated plates or activated HUVEC were quantified by enzyme-linked immunosorbent assay. E-selectin in the activated HUVEC was analyzed by immunoblot. RESULTS: Isoflurane and sevoflurane concentration-dependently suppressed adhesion of HL-60 cells to E-selectin-coated plates. Although isoflurane did not change the amount of expression, or the molecular weight of E-selectin in the activated HUVEC, it significantly suppressed HL-60 cell adhesion to activated HUVEC. CONCLUSION: Volatile anesthetics suppress E-selectin-mediated cell adhesion in a static condition without changing the expression of E-selectin. A role for E-selectin in the organ protection by volatile anesthetics is suggested.
Asunto(s)
Anestésicos por Inhalación/farmacología , Adhesión Celular/efectos de los fármacos , Selectina E/fisiología , Leucocitos/efectos de los fármacos , Línea Celular , Citocinas/farmacología , Selectina E/metabolismo , Células Endoteliales/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Células HL-60 , Humanos , Immunoblotting , Isoflurano/farmacología , Éteres Metílicos/farmacología , SevofluranoRESUMEN
PURPOSE: Volatile anesthetics affect the cardiovascular and immune systems. Toward a better understanding of the molecular mechanisms behind the modulation exerted by these agents, we focused on the effects of halothane and isoflurane on the activation of p38 mitogen-activated protein kinase (MAPK), which plays a critical role in the cellular responses to extracellular stimuli such as lipopolysaccharide (LPS) and proinflammatory cytokines, including tumor necrosis factor (TNF) and interleukin 1 (IL-1). METHODS: Human umbilical vein endothelial cells and HeLa cells, an established cell line, were examined by molecular biological methods. Cells were treated with proinflammatory compounds with or without the volatile anesthetics. p38 MAPK activation was investigated by Western blotting analysis with phosphospecific anti-p38 MAPK antibodies. RESULTS: Isoflurane activated p38 MAPK by itself, but halothane did not. Halothane or isoflurane augmented the LPS- and TNF-induced activation of p38 MAPK. In contrast, neither halothane nor isoflurane enhanced the p38 MAPK activation induced by IL-1. Neither of the anesthetics affected H(2)O(2) or MAPK kinase 3 (MKK3)-induced p38 MAPK activation. CONCLUSION: Our in vitro results indicate that the volatile anesthetics used in the clinical field and in animal experiments modify the p38 MAPK signaling cascade and suggest that the target molecules of the anesthetics are not unique and the anesthetics regulate them differentially at clinically relevant doses.
Asunto(s)
Anestésicos por Inhalación/farmacología , Citocinas/farmacología , Halotano/farmacología , Isoflurano/farmacología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Células Cultivadas , Células Endoteliales/efectos de los fármacos , Células Endoteliales/enzimología , Activación Enzimática/efectos de los fármacos , Humanos , Peróxido de Hidrógeno/farmacología , Interleucina-1/farmacología , Lipopolisacáridos/farmacología , MAP Quinasa Quinasa 3 , Quinasas de Proteína Quinasa Activadas por Mitógenos/fisiología , Proteínas Tirosina Quinasas/fisiología , Factor de Necrosis Tumoral alfa/farmacología , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
The intracellular generation of reactive oxygen species (ROS) by 6-formylpterin and its effects on the human T cell functions were examined in vitro. When T cells isolated from fresh blood were incubated with 6-formylpterin for 1hr, the oxygen consumption and concomitant ROS generation were observed. The incubation of T cells with 50-500microM 6-formylpterin for 24hr brought about the elevation of intracellular ROS without inducing cell death. In contrast, the incubation of T cells with exogenously administered hydrogen peroxide (H(2)O(2)) or other pterin derivatives (6-hydroxymethylpterin, pterin-6-carboxylic acid, pterin, neopterin, biopterin and folic acid) for 24hr did not cause the intracellular ROS elevation. In the T cells stimulated with mitogenic lectin phytohemagglutinin (PHA) in conjunction with phorbol myristate acetate (PMA), 6-formylpterin suppressed the NF-kappaB-dependent transcription, the production of cytokines (IFN-gamma and IL-2) and the cell proliferation. These suppressive effects of 6-formylpterin were all reversed by N-acetyl-l-cystein (NAC). However, 6-formylpterin did not inhibit the NF-kappaB-DNA binding of the nuclear extracts obtained from the PHA/PMA-stimulated T cells. Since the NF-kappaB-DNA binding assay performed in vitro merely shows the presence or absence of NF-kappaB subunit in the nuclear extracts but not guarantees the actual binding of NF-kappaB with DNA in the nucleus, these findings suggest that intracellular ROS generated by 6-formylpterin does not affect the translocation of NF-kappaB to the nucleus but that it inhibits the NF-kappaB-dependent transcription in the nucleus, resulting in the suppression of cytokine production and cell proliferation in the activated T cells.
Asunto(s)
Leucocitos Mononucleares/efectos de los fármacos , Pterinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Linfocitos T/efectos de los fármacos , Transporte Activo de Núcleo Celular/efectos de los fármacos , Adulto , División Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Citocinas/metabolismo , Humanos , Técnicas In Vitro , Leucocitos Mononucleares/metabolismo , FN-kappa B/metabolismo , Consumo de Oxígeno/efectos de los fármacos , Linfocitos T/metabolismo , Transcripción GenéticaRESUMEN
BACKGROUND: Actions of volatile anesthetics on ligand-gated ion channels, such as gamma-aminobutyric acid type A receptors, have been studied extensively. However, actions on other types of channels, such as K+ channels, are poorly understood. The authors previously showed that a Ca2+-activated K+ channel, IK, is sensitive to halothane, whereas SK1, another Ca2+-activated K+ channel, is insensitive. To explore how halothane acts on Ca2+-activated K+ channels, chimeras between IK and SK1 were constructed, and halothane sensitivity was analyzed. METHODS: IK, SK1, and chimera channels were expressed in Xenopus laevis oocytes. Currents of expressed channels were measured in the presence of 10 microm Ca2+ by excised patch clamp analysis. Time constants of inhibition by halothane were compared between inside-out and outside-out patch configurations. RESULTS: Currents from chimera channels possessing the pore domain derived from IK were inhibited by halothane, whereas those possessing the SK1 pore domain were insensitive. Time constants of inhibition by halothane were significantly smaller in the outside-out patches than in the inside-out patches of both wild-type IK and a chimera with pore domain of IK. CONCLUSIONS: It is suggested that halothane interacts with the extracellular part of the ionic pore of IK. Whether this type of interaction is involved in the mechanism of anesthetic actions on ligand-gated ion channels warrants further investigation.
Asunto(s)
Anestésicos por Inhalación/farmacología , Halotano/farmacología , Bloqueadores de los Canales de Potasio/farmacología , Canales de Potasio Calcio-Activados/antagonistas & inhibidores , Animales , Femenino , Canales de Potasio Calcio-Activados/química , Canales de Potasio Calcio-Activados/fisiología , Proteínas Recombinantes de Fusión/antagonistas & inhibidores , Xenopus laevisRESUMEN
Kartagener's syndrome is an inherited disease characterized by a triad of symptoms, bronchiectasis, situs inversus and sinusitus. We report a case of a 53-year-old woman with the syndrome who received bilateral simple mastectomies and axillary lymph node dissections on ambulatory basis. She received antibiotic treatment until the day of surgery. She was admitted to our day surgery unit with productive cough and rales on both lungs on the day of surgery. General anesthesia was induced and maintained with propofol, fentanyl and vecuronium. Laryngeal mask airway (LMA) was placed. She received rectal diclofenac and bupivacaine infiltration into surgical field for pain relief. During pressure controlled ventilation, EtCO2, blood pressure and heart rate increased and SpO2 decreased gradually. These symptoms were resolved after resumption of spontaneous ventilation. She coughed out phlegm in LMA during surgery. The sputa were sucked out using bronchofiberscope. She made an uneventful recovery although she had productive cough preoperatively. She was discharged from the hospital without respiratory complication after overnight observation.