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1.
Med. intensiva (Madr., Ed. impr.) ; 41(8): 461-467, nov. 2017. graf, tab
Article in Spanish | IBECS | ID: ibc-168423

ABSTRACT

Objetivo: Valorar el efecto de la FiO2 sobre el sesgo y la precisión en la medición del consumo de oxígeno (V˙O2) y la producción de dióxido de carbono (V˙CO2) con el monitor E-COVX en pacientes con ventilación mecánica. Diseño: Descriptivo de concordancia. Ámbito: Unidad de Cuidados Intensivos. Pacientes o participantes: Pacientes con ventilación mecánica. Intervenciones: Se midieron el V˙O2 y la V˙CO2 con el monitor E-COVX. Los valores de V˙O2 y V˙CO2 fueron el promedio de 5min. Dos grupos de 30 pacientes. Se analizó: 1) la reproducibilidad de la medición del V˙O2 y la V˙CO2 con una FiO2 de 0,4, y 2) el efecto de los cambios en la FiO2 sobre el V˙O2 y la V˙CO2. Análisis estadístico por el método de Bland y Altman. Variables de interés principales: Sesgo y precisión. Resultados: 1) Reproducibilidad a una FiO2 de 0,4: los sesgos en la medición del V˙O2 y la V˙CO2 fueron de 1,6 y 2,1mL/min, respectivamente, y los errores en la precisión fueron de 9,7 a −8,3% y de 7,2 a −5,2%, respectivamente, y 2) efecto de la FiO2 sobre el V˙O2: el sesgo del V˙O2 medido a una FiO2 de 0,4 y 0,6 fue de −4,0mL/min y a FiO2 de 0,4 y 0,8, de 5,2mL/min. La precisión entre FiO2 de 0,4 y 0,6 fue de 11,9 a −14,1%, y entre FiO2 de 0,4 y 0,8, de 43,9 a −39,7%. Conclusiones: El monitor E-COVX mide el V˙O2 y la V˙CO2 en pacientes críticos con ventilación mecánica con un sesgo y una precisión clínicamente aceptables hasta una FiO2 de 0,6 (AU)


Objective: We evaluated the effect of changes in FiO2 on the bias and accuracy of the determination of oxygen consumption (V˙O2) and carbon dioxide production (V˙CO2) using the E-COVX monitor in patients with mechanical ventilation. Design: Descriptive of concordance. Setting: Intensive Care Unit. Patients or participants: Patients with mechanical ventilation. Interventions: We measured V˙O2 and V˙CO2 using the E-COVX monitor. Values recorded were the average in 5min. Two groups of 30 patients. We analyzed: 1) the reproducibility in the measurement of V˙O2 and V˙CO2 at FiO2 0.4, and 2) the effect of the changes in FiO2 on the measurement of V˙O2 and V˙CO2. Statistical analysis was performed using Bland and Altman test. Variables of main interest: Bias and accuracy. Results: 1) FiO2 0.4 reproducibility: The bias in the measurement of V˙O2 and V˙CO2 was 1.6 and 2.1mL/min, respectively, and accuracy was 9.7 to −8.3% and 7.2 to −5.2%, respectively, and 2) effect of FiO2 on V˙O2: The bias of V˙O2 measured at FiO2 0.4 and 0.6 was −4.0mL/min and FiO2 0.4 and 0.8 was 5.2mL/min. Accuracy between FiO2 0.4 and 0.6 was 11.9 to −14.1%, and between FiO2 0.4 and 0.8 was 43.9 to −39.7%. Conclusions: The E-COVX monitor evaluates V˙O2 and V˙CO2 in critical patients with mechanical ventilation with a clinically acceptable accuracy until FiO2 0.6 (AU)


Subject(s)
Humans , Oxygen Consumption , Respiration, Artificial/methods , Carbon Dioxide/therapeutic use , Pulmonary Gas Exchange , Reproducibility of Results , Clinical Protocols , Calorimetry, Indirect , Intensive Care Units , Enteral Nutrition , Respiratory Rate
2.
Med. intensiva (Madr., Ed. impr.) ; 41(6): 330-338, ago.-sept. 2017. tab, graf
Article in English | IBECS | ID: ibc-165506

ABSTRACT

Objective: To evaluate the effect of enteral nutrition volume, gastrointestinal function and the type of acid suppressive drug upon the incidence of lower respiratory tract infections in critically ill patients on mechanical ventilation (MV). Design: A retrospective secondary analysis was carried out. Setting: The Intensive Care Unit of a University Hospital. Patients or participants: Patients≥18-years-old expected to need MV for more than four days, and receiving enteral nutrition by nasogastric tube within 24h of starting MV. Interventions: We correlated enteral nutrition volume administered during the first 10 days, gastrointestinal function and the type of acid suppressive therapy with the episodes of lower respiratory tract infection up until day 28. Cox proportional hazards ratios in univariate and adjusted multivariate models were used. Statistical significance was considered for p<0.05. Main variables of interest: Lower respiratory tract infection episodes. Results: Sixty-six out of 185 patients (35.7%) had infection; 27 patients had ventilator-associated pneumonia; and 39 presented ventilator-associated tracheobronchitis. Uninfected and infected groups were similar in terms of enteral nutrition volume (54±12 and 54±9mL/h; p=0.94) and caloric intake (19.4±4.9 and 19.6±5.2kcal/kg/d; p=0.81). The Cox proportional hazards model showed neurological indication of MV to be the only independent variable related to infection (p=0.001). Enteral nutrition volume, the type of acid suppressive therapy, and the use of prokinetic agents were not significantly correlated to infection. Conclusions: Enteral nutrition volume and caloric intake, gastrointestinal dysfunction and the type of acid suppressive therapy used were not associated to lower respiratory tract infection in patients on MV (AU)


Objetivo: Valorar el efecto del volumen de nutrición enteral, la función gastrointestinal y el tipo de protección gástrica en la incidencia de infección respiratoria del tracto inferior en pacientes críticos con ventilación mecánica (VM). Diseño: Análisis secundario retrospectivo. Ámbito: La Unidad de Cuidados Intensivos de un hospital universitario. Pacientes o participantes: Pacientes con edad≥18 años que se espera que precisen de VM durante>4 días y reciban nutrición enteral en las primeras 24h. Intervenciones: Correlacionamos el volumen de nutrición enteral administrado durante los primeros 10 días, la función gastrointestinal y el tipo de protección gástrica con los episodios de infección pulmonar del tracto inferior hasta el día 28. Utilizamos el modelo de regresión de Cox. Un valor de p<0,05 fue considerado estadísticamente significativo. Principal variable de interés: Episodios de infección del tracto respiratorio inferior. Resultados: Sesenta y seis de los 185 pacientes (35,7%) presentaron infección, 27 pacientes neumonía y 39 traqueobronquitis. Los pacientes no infectados e infectados fueron similares en el volumen de nutrición enteral (54±12 y 54±9mL/h; p=0,94) y aporte calórico (19,4±4,9 y 19,6±5,2kcal/kg/d; p=0,81). El modelo de regresión de Cox mostró que la causa neurológica de VM fue la única variable independiente asociada con infección (p=0,001). El volumen de nutrición enteral, el tipo de protección gástrica y la función gastrointestinal no se correlacionaron significativamente con la infección. Conclusiones: El volumen y aporte calórico de nutrición enteral, la disfunción gastrointestinal y el tipo de protección gástrica no se asociaron a la infección del tracto respiratorio inferior en pacientes con VM (AU)


Subject(s)
Humans , Pneumonia, Ventilator-Associated/epidemiology , Enteral Nutrition/methods , Critical Care/methods , Intensive Care Units/statistics & numerical data , Energy Intake/physiology , Retrospective Studies , Proton Pump Inhibitors/therapeutic use
3.
Med Intensiva ; 41(6): 330-338, 2017.
Article in English, Spanish | MEDLINE | ID: mdl-28292527

ABSTRACT

OBJECTIVE: To evaluate the effect of enteral nutrition volume, gastrointestinal function and the type of acid suppressive drug upon the incidence of lower respiratory tract infections in critically ill patients on mechanical ventilation (MV). DESIGN: A retrospective secondary analysis was carried out. SETTING: The Intensive Care Unit of a University Hospital. PATIENTS OR PARTICIPANTS: Patients≥18-years-old expected to need MV for more than four days, and receiving enteral nutrition by nasogastric tube within 24h of starting MV. INTERVENTIONS: We correlated enteral nutrition volume administered during the first 10 days, gastrointestinal function and the type of acid suppressive therapy with the episodes of lower respiratory tract infection up until day 28. Cox proportional hazards ratios in univariate and adjusted multivariate models were used. Statistical significance was considered for p<0.05. MAIN VARIABLES OF INTEREST: Lower respiratory tract infection episodes. RESULTS: Sixty-six out of 185 patients (35.7%) had infection; 27 patients had ventilator-associated pneumonia; and 39 presented ventilator-associated tracheobronchitis. Uninfected and infected groups were similar in terms of enteral nutrition volume (54±12 and 54±9mL/h; p=0.94) and caloric intake (19.4±4.9 and 19.6±5.2kcal/kg/d; p=0.81). The Cox proportional hazards model showed neurological indication of MV to be the only independent variable related to infection (p=0.001). Enteral nutrition volume, the type of acid suppressive therapy, and the use of prokinetic agents were not significantly correlated to infection. CONCLUSIONS: Enteral nutrition volume and caloric intake, gastrointestinal dysfunction and the type of acid suppressive therapy used were not associated to lower respiratory tract infection in patients on MV.


Subject(s)
Enteral Nutrition , Pneumonia, Ventilator-Associated/epidemiology , Respiration, Artificial , Respiratory Tract Infections/epidemiology , Critical Illness , Energy Intake , Enteral Nutrition/methods , Female , Gastrointestinal Tract/physiology , Humans , Incidence , Male , Middle Aged , Proton Pump Inhibitors/therapeutic use , Retrospective Studies
4.
Med Intensiva ; 41(8): 461-467, 2017 Nov.
Article in English, Spanish | MEDLINE | ID: mdl-28283325

ABSTRACT

OBJECTIVE: We evaluated the effect of changes in FiO2 on the bias and accuracy of the determination of oxygen consumption (V˙O2) and carbon dioxide production (V˙CO2) using the E-COVX monitor in patients with mechanical ventilation. DESIGN: Descriptive of concordance. SETTING: Intensive Care Unit. PATIENTS OR PARTICIPANTS: Patients with mechanical ventilation. INTERVENTIONS: We measured V˙O2 and V˙CO2 using the E-COVX monitor. Values recorded were the average in 5min. Two groups of 30 patients. We analyzed: 1) the reproducibility in the measurement of V˙O2 and V˙CO2 at FiO2 0.4, and 2) the effect of the changes in FiO2 on the measurement of V˙O2 and V˙CO2. Statistical analysis was performed using Bland and Altman test. VARIABLES OF MAIN INTEREST: Bias and accuracy. RESULTS: 1) FiO2 0.4 reproducibility: The bias in the measurement of V˙O2 and V˙CO2 was 1.6 and 2.1mL/min, respectively, and accuracy was 9.7 to -8.3% and 7.2 to -5.2%, respectively, and 2) effect of FiO2 on V˙O2: The bias of V˙O2 measured at FiO2 0.4 and 0.6 was -4.0mL/min and FiO2 0.4 and 0.8 was 5.2mL/min. Accuracy between FiO2 0.4 and 0.6 was 11.9 to -14.1%, and between FiO2 0.4 and 0.8 was 43.9 to -39.7%. CONCLUSIONS: The E-COVX monitor evaluates V˙O2 and V˙CO2 in critical patients with mechanical ventilation with a clinically acceptable accuracy until FiO2 0.6.


Subject(s)
Breath Tests/instrumentation , Carbon Dioxide/metabolism , Monitoring, Physiologic/instrumentation , Oxygen Consumption , Pulmonary Gas Exchange , Adult , Aged , Analgesics, Opioid/pharmacology , Calorimetry, Indirect , Critical Care , Energy Intake , Female , Humans , Hypnotics and Sedatives/pharmacology , Lung Volume Measurements/instrumentation , Male , Middle Aged , Oxygen/analysis , Reproducibility of Results , Respiration, Artificial
5.
Cuad. Hosp. Clín ; 58(2): 69-69, 2017.
Article in Spanish | LILACS | ID: biblio-972845

ABSTRACT

Objetivo. Valorar el efecto del volumen de nutrición enteral, la función gastrointestinal y el tipo de protección gástrica en la incidencia de infección respiratoria del tracto inferior en pacientes críticos con ventilación mecánica (VM). Diseño Análisis secundario retrospectivo. Ámbito La Unidad de Cuidados Intensivos de un hospital universitario. Pacientes o participantes Pacientes con edad≥18 años que se espera que precisen de VM durante>4 días y reciban nutrición enteral en las primeras 24h. Intervenciones Correlacionamos el volumen de nutrición enteral administrado durante los primeros 10 días, la función gastrointestinal y el tipo de protección gástrica con los episodios de infección pulmonar del tracto inferior hasta el día 28. Utilizamos el modelo de regresión de Cox. Un valor de p<0,05 fue considerado estadísticamente significativo. Principal variable de interés Episodios de infección del tracto respiratorio inferior. Resultados Sesenta y seis de los 185 pacientes (35,7 por ciento) presentaron infección, 27 pacientes neumonía y 39 traqueobronquitis. Los pacientes no infectados e infectados fueron similares en el volumen de nutrición enteral (54±12 y 54±9mL/h; p=0,94) y aporte calórico (19,4±4,9 y 19,6±5,2kcal/kg/d; p=0,81). El modelo de regresión de Cox mostró que la causa neurológica de VM fue la única variable independiente asociada con infección (p=0,001). El volumen de nutrición enteral, el tipo de protección gástrica y la función gastrointestinal no se correlacionaron significativamente con la infección. Conclusiones El volumen y aporte calórico de nutrición enteral, la disfunción gastrointestinal y el tipo de protección gástrica no se asociaron a la infección del tracto respiratorio inferior en pacientes con VM.


Subject(s)
Enteral Nutrition , Respiratory System , Ventilators, Mechanical
8.
J Intensive Care Med ; 31(1): 34-40, 2016 Jan.
Article in English | MEDLINE | ID: mdl-24578466

ABSTRACT

BACKGROUND: The role that intensive care unit (ICU)-acquired pneumonia plays in the long-term outcomes of cardiac surgery patients is not well known. This study examined the association of pneumonia with in-hospital mortality and long-term mortality after adult cardiac surgery. METHODS: A total of 2750 patients admitted to our ICU after cardiac surgery from January 2003 to December 2009 are the basis for this observational study. Patients who developed ICU-acquired pneumonia were matched with patients without it in a 1:2 ratio. The matching criteria were age, urgent or scheduled surgery, surgical procedure, and the propensity score for pneumonia. Multiple regression analysis was used to find predictors of hospital mortality. The relationship between pneumonia and long-term survival was analyzed with Kaplan-Meier survival estimates and a risk-adjusted Cox proportional regression model for patients discharged alive from hospital. RESULTS: Pneumonia was diagnosed in 32 (1.2%) patients and there were 19 cases per 1000 days of mechanical ventilation. Patients with pneumonia had a significantly higher hospital mortality rate (28% vs 6.2%, P = .003) and a higher mortality at the end of follow-up (53% vs 19%, P < .0001) than those without it. Regression analysis showed that pneumonia was a strong predictor of hospital mortality. Five-year survival was as follows: pneumonia, 62%; control, 81%; and cohort patients, 91%. The Cox model showed that, after adjusting for confounding factors, patients with pneumonia (hazard ratio = 3.96, 95% confidence interval [CI]: 1.41-11.14) had poorer long-term survival. CONCLUSION: Pneumonia remains a serious complication in patients operated for cardiac surgery and is associated with increased hospital mortality and reduced long-term survival.


Subject(s)
Cardiac Surgical Procedures/mortality , Intensive Care Units , Pneumonia, Ventilator-Associated/mortality , Postoperative Complications/mortality , Propensity Score , Cardiac Surgical Procedures/adverse effects , Case-Control Studies , Cross Infection , Hospital Mortality , Humans , Pneumonia, Ventilator-Associated/microbiology , Postoperative Complications/etiology , Postoperative Complications/microbiology , Proportional Hazards Models , Spain/epidemiology , Treatment Outcome
9.
Acta Neurol Scand ; 132(5): 337-45, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25903789

ABSTRACT

OBJECTIVES: Lacosamide is indicated for the adjunctive treatment of partial-onset seizures in adult patients. Unlike other sodium channel-blocking antiepileptic drugs, lacosamide selectively enhances sodium channel slow inactivation. Potential effects of lacosamide on cardiac sodium channels and their cardiovascular consequences were comprehensively assessed. This manuscript presents the non-clinical cardiac safety profile of lacosamide. METHODS: Lacosamide was tested in vitro on sodium and L-type calcium currents from isolated human atrial myocytes and on hERG-mediated potassium currents from stably transfected HEK293 cells. Cardiac action potentials were recorded in guinea pig ventricular myocytes. In vivo, hemodynamic and ECG parameters were evaluated in anesthetized dogs and monkeys receiving acute cumulative intravenous doses of lacosamide. RESULTS: Following intravenous dosing with lacosamide, dose-dependent PR and QRS prolongation and ECG abnormalities (loss of P waves, atrioventricular and intraventricular blocks, junctional premature contractions) were observed in anesthetized dogs and monkeys. In vitro, lacosamide reduced human cardiac sodium currents in a concentration-, voltage- and state-dependent manner. Lacosamide reductions in Vmax in guinea pig myocytes were similar to lamotrigine and carbamazepine. Lacosamide showed no relevant inhibitory effects on hERG and L-type calcium channels and did not prolong QTc in vivo. CONCLUSIONS: ECG findings in anesthetized animals correlate well with in vitro sodium channel-related effects and are also consistent with those (PR prolongation, first-degree atrioventricular block) reported in healthy volunteers and patients with epilepsy. Both in vivo and in vitro effects were detected from exposure levels 1.5- to 2-fold above those achieved with the maximum-recommended human lacosamide dose (400 mg/day).


Subject(s)
Acetamides/adverse effects , Action Potentials/drug effects , Anticonvulsants/adverse effects , Heart Rate/drug effects , Acetamides/administration & dosage , Acetamides/pharmacology , Adult , Animals , Anticonvulsants/administration & dosage , Anticonvulsants/pharmacology , Cardiotoxicity , Cells, Cultured , Dogs , Ether-A-Go-Go Potassium Channels/metabolism , Guinea Pigs , HEK293 Cells , Haplorhini , Humans , Lacosamide , Sodium Channels/metabolism
10.
Med. intensiva (Madr., Ed. impr.) ; 38(7): 422-429, oct. 2014. ilus, tab
Article in Spanish | IBECS | ID: ibc-127658

ABSTRACT

OBJETIVO: Averiguar si existe asociación entre la transfusión perioperatoria de 1-2 unidades de hematíes y la morbilidad hospitalaria, la mortalidad a 30 días y la supervivencia a largo plazo en los pacientes operados en cirugía cardíaca. DISEÑO: Estudio de cohorte prospectivo. Ámbito: UCI de un hospital universitario. PACIENTES: Se valoró a todos los pacientes mayores de 17 años operados de cirugía cardíaca e ingresados en la UCI desde noviembre del 2002 hasta diciembre del 2009. Se analizó a los pacientes que no recibieron transfusión de hematíes (n = 703) y a los que recibieron transfusión perioperatoria de 1-2 unidades de hematíes (n = 959). Variables de interés: Se analizó el efecto de la transfusión sobre la morbilidad hospitalaria y la mortalidad a 30 días. El seguimiento de los enfermos dados de alta vivos del hospital finalizó el 31 de diciembre del 2011. La asociación de la transfusión con la supervivencia a largo plazo se evaluó con el método de Kaplan-Meier. La evaluación de los posibles factores predictivos de mortalidad a largo plazo se realizó mediante la construcción de modelos de regresión de Cox. RESULTADOS: La frecuencia de complicaciones postoperatorias cardíacas y no cardíacas fue mayor en los pacientes que recibieron transfusión. La mortalidad a 30 días de estos últimos fue mayor que en los pacientes no transfundidos (1% vs. 0,1%, p = 0,02). La presencia de anemia preoperatoria se asoció a un mayor uso de transfusión. La transfusión de hematíes no fue un factor de riesgo de mortalidad a largo plazo (Hazard ratio = 1,4; intervalo de confianza del 95%, 0,9-2,1). CONCLUSIONES: La transfusión perioperatoria de 1-2 unidades de hematíes en los pacientes operados de cirugía cardíaca se asocia a un incremento de la morbilidad hospitalaria y la mortalidad a 30 días, y no tiene efecto en la mortalidad a largo plazo


OBJECTIVE: A study was made to explore the possible association between the perioperative transfusion of 1 - 2 red blood cell units and in-hospital morbidity, 30-day mortality, and long-term survival in patients undergoing heart surgery. DESIGN: A prospective observational study was carried out. SETTING: The ICU of a university hospital. PATIENTS: All patients over 17 years of age that underwent heart surgery and were admitted to the ICU between November 2002 and December 2009 were included. Those patients who did not (n = 703) and those who did (n = 959) receive the perioperative transfusion of 1 - 2 red blood cell units were assessed. Study endpoints: The endpoints were the effect of transfusion on both hospital morbidity and on 30-day mortality. In addition, all patients discharged alive from hospital until 31 December 2011 were subjected to follow-up. The association between transfusion and survival was assessed by means of the Kaplan-Meier method. Cox proportional hazards models were used to assess factors associated with long-term survival. RESULTS: The frequency of both cardiac and non-cardiac perioperative complications was higher in patients receiving transfusion. The 30-day mortality rate was higher in those who received transfusion (1% vs 0.1%, P = .02). Preoperative anemia was associated with a more intensive use of transfusion. Red blood cell transfusion was not found to be a risk factor for long-term mortality (hazar ratio = 1.4, 95% CI 0.9-2.1). CONCLUSIONS: The perioperative transfusion of 1 - 2 red blood cell units in patients undergoing heart surgery increases both hospital morbidity and the 30-day mortality rate, but does not increase long-term mortality


Subject(s)
Humans , Erythrocyte Transfusion , Cardiac Surgical Procedures/statistics & numerical data , Disease-Free Survival , Critical Care/methods , Intensive Care Units/statistics & numerical data , Time/statistics & numerical data , Indicators of Morbidity and Mortality
11.
Med Intensiva ; 38(7): 422-9, 2014 Oct.
Article in Spanish | MEDLINE | ID: mdl-24315133

ABSTRACT

OBJECTIVE: A study was made to explore the possible association between the perioperative transfusion of 1 - 2 red blood cell units and in-hospital morbidity, 30-day mortality, and long-term survival in patients undergoing heart surgery. DESIGN: A prospective observational study was carried out. SETTING: The ICU of a university hospital. PATIENTS: All patients over 17 years of age that underwent heart surgery and were admitted to the ICU between November 2002 and December 2009 were included. Those patients who did not (n=703) and those who did (n=959) receive the perioperative transfusion of 1 - 2 red blood cell units were assessed. STUDY ENDPOINTS: The endpoints were the effect of transfusion on both hospital morbidity and on 30-day mortality. In addition, all patients discharged alive from hospital until 31 December 2011 were subjected to follow-up. The association between transfusion and survival was assessed by means of the Kaplan-Meier method. Cox proportional hazards models were used to assess factors associated with long-term survival. RESULTS: The frequency of both cardiac and non-cardiac perioperative complications was higher in patients receiving transfusion. The 30-day mortality rate was higher in those who received transfusion (1% vs 0.1%, P=.02). Preoperative anemia was associated with a more intensive use of transfusion. Red blood cell transfusion was not found to be a risk factor for long-term mortality (hazar ratio=1.4, 95%CI 0.9-2.1). CONCLUSIONS: The perioperative transfusion of 1 - 2 red blood cell units in patients undergoing heart surgery increases both hospital morbidity and the 30-day mortality rate, but does not increase long-term mortality.


Subject(s)
Coronary Disease/surgery , Erythrocyte Transfusion/statistics & numerical data , Heart Valve Diseases/surgery , Aged , Aged, 80 and over , Cardiac Surgical Procedures/mortality , Coronary Disease/mortality , Female , Heart Valve Diseases/mortality , Humans , Male , Middle Aged , Prospective Studies , Survival Rate , Time Factors
14.
Eur J Neurosci ; 14(6): 927-36, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11595031

ABSTRACT

Extracellular ATP, by acting on P2 purinergic receptors, is a potent mediator of cell-to-cell communication both within and between the nervous and the immune systems. We show here by patch-clamp recording, fluorescent dye uptake and immunocytochemistry that, in cultured mouse Schwann cells, ATP activates a P2X(7) receptor associated with three different ionic conductances. In control conditions, ATP activated an inward current (I(ATP)) with a low potency (EC(50), 7.2 mM). Replacing ATP either by the ATP analogue 2',3'-O-(4-benzoyl-4-benzoyl)-ATP (BzATP) or by the tetraacidic form ATP(4-) potentiated the inward current (ATP(4-) EC(50), 375 microM). ATP and BzATP currents were strongly reduced by periodate oxidized ATP (oATP), an antagonist of P2X(7) receptors. IATP was a mixed current composed of a nonselective cationic conductance, a cationic conductance selective for K(+) and an anionic conductance selective for Cl(-). The activation of the K(+) conductance was dependent on an influx of Ca(2+), and was blocked by charybdotoxin (ChTX) and tetraethylammonium (TEA), two potent antagonists of large conductance Ca(2+)-activated K(+) channels (BK channels). The activation of the Cl(-) conductance was insensitive to Ca(2+) but required the presence of K(+). Total removal of K(+) blocked both the Ca(2+)-activated K(+) conductance and the Cl(-) conductance, unveiling the P2X(7) nonselective cationic conductance. The P2X(7) receptor was localized by immunocytochemistry using a polyclonal antibody, anti-P2X(7), whilst its expression and functionality were both detected by the uptake of Lucifer Yellow. This receptor could regulate the synthesis and the release of cytokines by Schwann cells during pathophysiological events.


Subject(s)
Adenosine Triphosphate/pharmacology , Egtazic Acid/analogs & derivatives , Ion Channels/agonists , Purinergic P2 Receptor Agonists , Schwann Cells/metabolism , Adenosine Triphosphate/analogs & derivatives , Animals , Biotransformation/drug effects , Calcium/physiology , Cells, Cultured , Chelating Agents/pharmacology , Culture Media , Egtazic Acid/pharmacology , Electrophysiology , Immunohistochemistry , Membrane Potentials/drug effects , Mice , Neuroglia/drug effects , Neuroglia/metabolism , Neuromuscular Junction/drug effects , Neuromuscular Junction/physiology , Patch-Clamp Techniques , Potassium/metabolism , Potassium/pharmacology , Receptors, Purinergic P2X7 , Schwann Cells/drug effects
15.
Glia ; 29(3): 281-7, 2000 Feb 01.
Article in English | MEDLINE | ID: mdl-10642754

ABSTRACT

It is well established that neurons regulate the properties of both central and peripheral glial cells. Some of these neuro-glial interactions are modulated by the pattern of neuronal electrical activity. In the present work, we asked whether blocking the electrical activity of dorsal root ganglion (DRG) neurons in vitro by a chronic treatment with tetrodotoxin (TTX) would modulate the expression of the T-type Ca(2+) channel by mouse Schwann cells. When recorded in their culture medium, about one-half of the DRG neurons spontaneously fired action potentials (APs). Treatment for 4 days with 1 microM TTX abolished both spontaneous and evoked APs in DRG neurons and in parallel significantly reduced the percentage of Schwann cells expressing Ca(2+) channel currents. On the fraction of Schwann cells still expressing Ca(2+) channel currents, these currents had electrophysiological parameters (mean amplitude, mean inactivation time constant, steady-state inactivation curve) similar to those of control cultures. Co-treatment for 4 days with 1 microM TTX and 2 mM CPT-cAMP, a cAMP analogue that induces the expression de novo of Ca(2+) channel currents in Schwann cells deprived of neurons, maintained the percentage of Schwann cells expressing Ca(2+) channel currents, showing that TTX does not directly affect the expression of Ca(2+) channel currents by Schwann cell. We conclude that blocking spontaneous activity of DRG neurons in vitro downregulates Ca(2+) channel expression by Schwann cells. These results strongly suggest that DRG neurons upregulate Ca(2+) channel expression by Schwann cells via the release of a diffusible factor whose secretion is dependent on electrical activity.


Subject(s)
Calcium Channels/metabolism , Ganglia, Spinal/embryology , Neurons/physiology , Schwann Cells/metabolism , Animals , Calcium Channels/drug effects , Electric Conductivity , Electrophysiology , Embryo, Mammalian , Ganglia, Spinal/drug effects , Mice , Neurons/drug effects , Organ Culture Techniques , Tetrodotoxin/pharmacology , Up-Regulation
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