RESUMO
OBJECTIVE: To describe, from the point of view of anesthesia and intensive care specialists, the perioperative management of high-risk patients with aortic stenosis who underwent transcatheter (transfemoral and transapical) aortic valve implantation (TAVI). The authors specifically focused on immediate postoperative complications. DESIGN: Retrospective review of collected data. SETTING: Academic hospital. PARTICIPANTS: Ninety consecutive patients with severe aortic stenosis who underwent TAVI. INTERVENTIONS: General anesthesia followed by postoperative care. Complications were defined by pre-established criteria. MEASUREMENTS AND MAIN RESULTS: Of 184 patients referred between October 2006 and February 2009, 90 were consecutively treated with TAVI because of a high surgical risk or contraindications to surgery. The transfemoral approach was used as the first option (n = 62), and the transapical approach when contraindications to the former were present (n = 28). Results are presented as mean ± standard deviation or median (25-75 percentiles) as appropriate. Patients were 81 ± 8 years old, in New York Heart Association classes II (9%), III (54 %), or IV (37%); left ventricular ejection fraction was below 0.5 in 38% of patients. The predicted surgical mortality was 24% (16-32) and 15% (11-23) with the logistic EuroSCORE and STS-Predicted Risk of Mortality, respectively. The valve was implanted in 92% of the cases. The duration of anesthesia and (intra- and postoperative) mechanical ventilation was 190 (160-230) minutes and 245 (180-420) minutes, respectively. Hospital mortality was 11%. The most frequent cardiac complications were heart failure (20%) and atrioventricular block (16%), with 6% requiring a pacemaker. Vascular complications (major and minor) occurred in 29% of the patients. CONCLUSIONS: Despite their severe comorbidities, the mortality of the patients in this cohort was below that predicted by cardiac surgery risk scores. Monitoring, hemodynamic instability, and the frequency of complications require management and follow-up of these patients in similar ways as for open cardiac surgery. The frequency of complications in this cohort was comparable to that published by other groups.
Assuntos
Anestesia Geral/efeitos adversos , Estenose da Valva Aórtica/cirurgia , Cateterismo Cardíaco/efeitos adversos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/etiologia , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral/mortalidade , Estenose da Valva Aórtica/mortalidade , Cateterismo Cardíaco/mortalidade , Estudos de Coortes , Gerenciamento Clínico , Feminino , Seguimentos , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Masculino , Complicações Pós-Operatórias/mortalidade , Estudos RetrospectivosRESUMO
INTRODUCTION: The main objective was to determine risk factors for presence of multidrug resistant bacteria (MDR) in postoperative peritonitis (PP) and optimal empirical antibiotic therapy (EA) among options proposed by Infectious Disease Society of America and the Surgical Infection Society guidelines. METHODS: One hundred patients hospitalised in the intensive care unit (ICU) for PP were reviewed. Clinical and microbiologic data, EA and its adequacy were analysed. The in vitro activities of 9 antibiotics in relation to the cultured bacteria were assessed to propose the most adequate EA among 17 regimens in the largest number of cases. RESULTS: A total of 269 bacteria was cultured in 100 patients including 41 episodes with MDR. According to logistic regression analysis, the use of broad-spectrum antibiotic between initial intervention and reoperation was the only significant risk factor for emergence of MDR bacteria (odds ratio (OR) = 5.1; 95% confidence interval (CI) = 1.7 - 15; P = 0.0031). Antibiotics providing the best activity rate were imipenem/cilastatin (68%) and piperacillin/tazobactam (53%). The best adequacy for EA was obtained by combinations of imipenem/cilastatin or piperacillin/tazobactam, amikacin and a glycopeptide, with values reaching 99% and 94%, respectively. Imipenem/cilastin was the only single-drug regimen providing an adequacy superior to 80% in the absence of broad spectrum antibiotic between initial surgery and reoperation. CONCLUSIONS: Interval antibiotic therapy is associated with the presence of MDR bacteria. Not all regimens proposed by Infectious Disease Society of America and the Surgical Infection Society guidelines for PP can provide an acceptable rate of adequacy. Monotherapy with imipenem/cilastin is suitable for EA only in absence of this risk factor for MDR. For other patients, only antibiotic combinations may achieve high adequacy rates.
Assuntos
Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Resistência Microbiana a Medicamentos , Resistência a Múltiplos Medicamentos , Peritonite/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Conflicting results have been reported on the effect of anxiety on the propofol dose required for inducing loss of consciousness (LOC). The hemodynamic effects of anxiety, increased heart rate (HR), and cardiac output may account for these discrepancies. We therefore designed this study to address, first, the effect of perioperative HR on propofol dose required for LOC and, second, the effect of perioperative anxiety on HR. METHODS: Forty-five ASA physical status I-II female patients undergoing gynecological surgery were studied. Anxiety was assessed in the operating room with the State-Trait Anxiety Inventory (STAI)-state Spielberger scale (situational anxiety). After HR recording, anesthesia was induced with a 200-mL/h 1% propofol infusion with the Base Primea pump (Fresenius-Vial, Brezins, France) until LOC. The propofol dose was recorded at the time of LOC. Relationships between STAI-state and HR versus propofol dose at LOC were tested with the Spearman test with a P value of 0.01. RESULTS: A significant relationship was observed between HR and propofol dose at LOC (rho = 0.487, P = 0.0012) but not between STAI-state and propofol dose (rho = 0.330, P = 0.0306). However, a significant relationship was observed between STAI-state and HR (rho = 0.462 and P = 0.0054). CONCLUSION: Increased perioperative HR is associated with increased propofol dose required for LOC. Perioperative anxiety accounts for increased HR.
Assuntos
Anestesia Intravenosa , Anestésicos Intravenosos , Ansiedade/fisiopatologia , Frequência Cardíaca/fisiologia , Hipnóticos e Sedativos , Propofol , Inconsciência/psicologia , Adolescente , Adulto , Idoso , Ansiedade/psicologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória , Propofol/administração & dosagem , Escalas de Graduação Psiquiátrica , Inconsciência/induzido quimicamente , Adulto JovemRESUMO
BACKGROUND: Pregnancy is associated with decreased hypnotic requirement, allegedly related to progesterone. However, the effects of pregnancy and progesterone on propofol requirement have not been thoroughly investigated. We conducted this study to determine whether propofol dose and predicted effect-site concentration for loss of consciousness (LOC) during induction of anesthesia, and eye opening during emergence from anesthesia, are decreased during early pregnancy. We also investigated whether blood progesterone was correlated with propofol dose and effect-site concentration for LOC. METHODS: We studied 57 ASA I-II women patients undergoing elective termination of pregnancy and 55 control patients undergoing transvaginal oocyte puncture for in vitro fertilization. Anesthesia was induced by administration of a 1% propofol infusion at 200 mL/min. Propofol dose and calculated effect-site concentration (Schnider model) were recorded at the time of LOC during induction. We also calculated effect-site concentration at the time of eye opening upon emergence from anesthesia. Blood progesterone was measured after surgery. RESULTS: Mean (+/-1 SD) propofol dose at LOC was significantly reduced in the pregnant patients compared with the nonpregnant control patients (108.57 +/- 20.04 vs 117.59 +/- 17.98 mg, respectively; P = 0.014). Similarly, the calculated propofol effect-site concentration at LOC was significantly lower in the pregnant patients than the nonpregnant control patients (4.59 +/- 0.72 vs 5.01 +/- 0.64 microg/mL, respectively; P = 0.0014). There was no difference in the calculated effect-site concentration on eye opening upon emergence. No significant relationship was observed between blood progesterone and propofol dose or calculated propofol effect-site concentration at LOC. CONCLUSION: Propofol dose and predicted propofol effect-site concentration at LOC are decreased during early pregnancy. Progesterone does not explain this result.
Assuntos
Período de Recuperação da Anestesia , Anestésicos Intravenosos/administração & dosagem , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Propofol/administração & dosagem , Adulto , Relação Dose-Resposta a Droga , Feminino , Humanos , Valor Preditivo dos Testes , Gravidez , Primeiro Trimestre da Gravidez/sangue , Adulto JovemAssuntos
Anestesia por Condução/efeitos adversos , Anestesia Geral/efeitos adversos , Cegueira , Neuropatia Óptica Isquêmica , Procedimentos Cirúrgicos Operatórios , Idoso , Anestesia por Condução/métodos , Anestesia Geral/métodos , Cegueira/etiologia , Cegueira/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuropatia Óptica Isquêmica/etiologia , Neuropatia Óptica Isquêmica/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND: To report the prognosis and management of patients reoperated for severe intraabdominal sepsis (IAS) after bariatric surgery (S0) and admitted to the surgical intensive care unit (ICU) for organ failure. METHODS: A French observational study in a 12-bed adult surgical intensive care unit in a 1,200-bed teaching hospital with expertise in bariatric surgery. From January 2001 to August 2006, 27 morbidly obese patients (18 transferred from other institutions) developed severe postoperative IAS (within 45 days). Clinical signs, biochemical and radiologic findings, and treatment during the postoperative course after S0 were reviewed. Time to reoperation, characteristics of IAS, demographic data, and disease severity scores at ICU admission were recorded and their influence on prognosis was analyzed. RESULTS: The presence of respiratory signs after S0 led to an incorrect diagnosis in more than 50% of the patients. Preoperative weight (body mass index [BMI] > 50 kg/m2) and multiple reoperations were associated with a poorer prognosis in the ICU. The ICU mortality rate was 33% and increased with the number of organ failures at reoperation. CONCLUSION: During the initial postoperative course after bariatric surgery, physical examination of the abdomen is unreliable to identify surgical complications. The presence of respiratory signs should prompt abdominal investigations before the onset of organ failure. An urgent laparoscopy, as soon as abnormal clinical events are detected, is a valuable tool for early diagnosis and could shorten the delay in treatment.
Assuntos
Cirurgia Bariátrica/mortalidade , Obesidade Mórbida/cirurgia , Adulto , Cuidados Críticos , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/mortalidade , Reoperação/mortalidade , Sepse/mortalidadeRESUMO
In critically ill patients, dosage adjustment of voriconazole could be helpful when high-volume continuous venovenous hemofiltration is needed. Voriconazole pharmacokinetics were studied in an anuric critically ill patient, under high-volume continuous venovenous hemofiltration, over an interval period after a 4-mg/kg dose of voriconazole. Arterial and effluent voriconazole concentrations were measured after liquid phase extraction using a high-pressure liquid chromatography. The extrapolate area under the curve(0-12h) of voriconazole was 65 mg/h/L. The total body clearance of voriconazole was 5.4 L/h with a half-life of 16.5 hours and a distribution volume of 128.6 L. The estimated sieving coefficient was 0.58 and the filtration clearance 1.39 L/h. High-volume continuous venovenous hemofiltration could affect voriconazole disposition in contrast with other techniques. Besides, we observed voriconazole accumulation consequence of the saturation of the metabolic clearance resulting from multiple organ failure. Dosage adjustment seems to be required in these conditions, but this observation must be confirmed by a clinical study.
Assuntos
Injúria Renal Aguda/terapia , Antifúngicos/farmacocinética , Aspergilose/tratamento farmacológico , Pirimidinas/farmacocinética , Triazóis/farmacocinética , Injúria Renal Aguda/complicações , Idoso , Antifúngicos/sangue , Área Sob a Curva , Aspergilose/complicações , Estado Terminal , Evolução Fatal , Meia-Vida , Hemofiltração , Humanos , Masculino , Taxa de Depuração Metabólica , Pirimidinas/sangue , Triazóis/sangue , VoriconazolRESUMO
The objective of this study was to evaluate the prevalence of 4 virulence factors (VFs) of enterococci (cytolysin [cyl], gelatinase [gel], aggregation substance [agg], and enterococcal surface protein [esp]) and their relationship to outcome in patients with generalized peritonitis in a prospective cohort study. VF expression in each strain was assessed by polymerase chain reaction assay with specific primers. Outcome of the patients was recorded. Ninety-nine strains of Enterococcus were obtained from the peritoneal fluid of 81 patients. Fifty-eight patients had at least 1 strain bearing [cyl] (13.1% of the strains), [gel] (50.5% of the strains), [agg] (40.4% of the strains), and [esp] (34.3% of the strains). The presence of VF of Enterococcus was independently associated with mortality: odds ratio, 5.5; 95% confidence interval, 1.3-28.1. In conclusion, VF accounted for 72% of the patients with enterococci isolated from the peritoneal fluid and was independently associated with mortality in severe peritonitis.
Assuntos
Enterococcus/isolamento & purificação , Enterococcus/fisiologia , Peritonite/microbiologia , Peritonite/mortalidade , Fatores de Virulência/análise , Fatores de Virulência/genética , Adulto , Idoso , Proteínas de Bactérias/análise , Proteínas de Bactérias/genética , Bacteriocinas/análise , Bacteriocinas/genética , Feminino , Gelatinases/análise , Gelatinases/genética , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Peritonite/tratamento farmacológico , Reação em Cadeia da Polimerase , Estudos Prospectivos , Resultado do TratamentoRESUMO
Obstructive sleep apnea (OSA) is associated with impaired airway reflexes. Cough is the main airway defense mechanism but the effect of OSA on cough is unknown. Thirty-two female obese patients scheduled to undergo bariatric surgery were studied. They were classified as presenting OSA (20 patients) when the apnea-hypopnea index (AHI) was greater than 5h. Cough sensitivity was measured with citric acid. Increasing concentrations of nebulized citric acid were delivered until cough was elicited. The concentrations eliciting one (C1) and two coughs (C2) were recorded and log transformed (log C1 and log C2). log C1 and log C2 (median (interquartile)) were 1.90 mg/mL (0.90) and 2.2mg/mL (0.30) in OSA patients and 1.60 mg/mL (0.45) and 1.60 mg/mL (0.45) in non-OSA patients, respectively (comparison between groups: p=0.0372 for log C1 and p=0.0227 for log C2). A significant relationship was observed between AHI and log C1 and log C2. Cough sensitivity is therefore, decreased in female obese OSA patients and this decreased sensitivity is positively correlated with disease severity.
Assuntos
Tosse/fisiopatologia , Obesidade Mórbida/fisiopatologia , Reflexo/fisiologia , Testes de Função Respiratória , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/fisiopatologia , Adolescente , Adulto , Cirurgia Bariátrica , Feminino , Volume Expiratório Forçado , Humanos , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Seleção de Pacientes , Valores de Referência , Abandono do Hábito de Fumar , Capacidade VitalRESUMO
The superiority of the left internal mammary artery (LIMA) graft over autogenous saphenous vein as a bypass conduit in coronary artery bypass surgery has been well established. Early and late patency rates of bilateral internal mammary artery (BIMA) grafts exceed those of vein grafts, and patients who receive BIMA have improved long-term survival rates and more freedom from reoperations and other cardiac events. But because of other concerns, particularly the question of increased risk of postoperative bleeding, controversy still surrounds the perioperative period. In the present study we sought to determine whether BIMA grafting was an independent risk factor of postoperative bleeding and of blood product use in patients undergoing primary elective coronary artery revascularization. For this purpose, 33 consecutive patients scheduled for BIMA grafting were matched with 66 patients operated on by single LIMA grafting. Patients in the LIMA group had significantly less postoperative mediastinal drainage than those in the BIMA group (median: 722 vs 920 mL, P = 0.0001). Fifty-six patients received blood products (56% vs 51% in LIMA and BIMA groups, respectively; P = 0.67). In multivariate analysis, BIMA and operative duration were independent predictors of increased postoperative drainage. Nevertheless, in logistic regression, BIMA was not significantly associated with blood product use, unlike precardiopulmonary bypass hematocrit and duration of surgery (OR and 95% CI: 0.89 [0.80-0.96] P = 0.01; 1.009 [1.001-1.019] P = 0.04, for an increase of 1% in hematocrit and 1 min in duration of surgery, respectively). In conclusion, these data support the idea that BIMA graft slightly increases postoperative drainage but not transfusion requirement.
Assuntos
Transfusão de Sangue , Drenagem , Anastomose de Artéria Torácica Interna-Coronária/métodos , Complicações Pós-Operatórias/terapia , Adulto , Idoso , Feminino , Humanos , Anastomose de Artéria Torácica Interna-Coronária/efeitos adversos , Masculino , Mediastino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/terapia , Fatores de RiscoAssuntos
Dispneia/etiologia , Transplante de Coração/efeitos adversos , Embolia Pulmonar/complicações , Diagnóstico Diferencial , Dispneia/diagnóstico , Seguimentos , Cardiopatias/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Embolia Pulmonar/diagnóstico , Fatores de Tempo , Tomografia Computadorizada por Raios X , Ultrassonografia DopplerRESUMO
OBJECTIVE: The purpose of the present study was to evaluate the prognostic implications of perioperative B-type natriuretic peptide (BNP) and cardiac troponin I concentrations in patients undergoing cardiopulmonary bypass for cardiac surgery. DESIGN: Prospective observational study. SETTING: Biochemistry laboratory and surgical care unit in a university hospital. PATIENTS: A total of 92 consecutive patients undergoing elective coronary artery (43 patients) or valve surgery (49 patients). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: BNP and cardiac troponin I concentrations were measured before surgery (day 0), and at day 1 after surgery. Postoperative cardiac dysfunction was defined as low cardiac output or hemodynamic instability requiring inotropic support for >24 hrs or congestive heart failure until day 5. One-year survival was also evaluated. Univariate and multivariate analyses were performed. An important BNP secretion was systematically observed after cardiac surgery. Independent predictors of cardiac dysfunction were preoperative New York Health Association class and BNP and cardiac troponin I concentrations measured at day 1. Patients with an elevation of both markers have a 12-fold increased risk of postoperative heart failure. The use of both markers in combination predicted better postoperative heart failure than each one separately. Age, low preoperative left ventricular ejection fraction, and elevated BNP at day 1 (>352 pg/mL) were associated with an increased mortality rate at 1 yr. In multivariate analysis, only left ventricular ejection fraction was significantly associated with 1-yr survival. CONCLUSIONS: Postoperative plasma BNP and cardiac troponin I levels are independent predictors of postoperative cardiac dysfunction after cardiac surgery. Simultaneous measurement of BNP and cardiac troponin I improve the risk assessment of postoperative cardiac dysfunction. However, the association between BNP levels and 1-yr outcome was no longer significant after adjustment on left ventricular ejection fraction.
Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiopatias/sangue , Cardiopatias/mortalidade , Peptídeo Natriurético Encefálico/sangue , Troponina I/sangue , Idoso , Feminino , Cardiopatias/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de TempoRESUMO
UNLABELLED: Urinary retention is a common postoperative complication associated with bladder overdistension and the risk of permanent detrusor damage. The goal of this study was to determine predictive factors of early postoperative urinary retention in the postanesthesia care unit (PACU). We prospectively collected, in 313 adult patients, variables including age, gender, previous history of urinary tract symptoms, type of surgery and anesthesia, intraoperative administration of anticholinergics, amount of intraoperative fluids, IV morphine titration, and bladder volume on entry to the PACU. For each patient, bladder volume was measured by ultrasound on entry and before discharge from the PACU. Urinary retention was defined as a bladder volume larger than 600 mL with an inability to void within 30 min. Predictive factors were identified by multivariate analysis. The incidence of urinary retention in the PACU was 16%. In the multivariate analysis only the amount of intraoperative fluids (>or=750 mL; P = 0.02; odds ratio = 2.3), age (>or=50 yr; P = 0.008; odds ratio = 2.4), and bladder volume on entry to PACU (>or=270 mL; P = 0.0001; odds ratio = 4.8) were found to independently increase the risk of urinary retention. Considering the clinical impact of undiagnosed postoperative urinary retention, these results suggest systematic evaluation of bladder volume with a portable ultrasound device in the PACU, especially in patients with risk factors. IMPLICATIONS: In this observational study, the ultrasound monitoring of bladder volume in the postanesthesia care unit (PACU) revealed that postoperative urinary retention occurred with an incidence of 16%. Age (>or=50 yr), amount of intraoperative fluid volume (>or=750 mL), and bladder volume on entry to PACU (>or=270 mL) were independent predictive factors for this complication.
Assuntos
Complicações Pós-Operatórias/diagnóstico , Retenção Urinária/diagnóstico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Anestesia , Antagonistas Colinérgicos/farmacologia , Estudos de Coortes , Feminino , Hidratação , Humanos , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Sala de Recuperação , Fatores Sexuais , Bexiga Urinária/anatomia & histologia , Retenção Urinária/epidemiologiaRESUMO
OBJECTIVE: Polymorphonuclear neutrophil (PMN) influx and peritoneal tumor necrosis factor (TNF)-alpha production are key host defense mechanisms during peritonitis. The aim of this study was to explore the potential interactions between TNF-alpha production and TNF-alpha converting enzyme (TACE) expression by PMN in the blood and peritoneum of patients with severe peritonitis. DESIGN: A prospective study. SETTING: A surgical adult intensive care unit in a university hospital. PATIENTS: A total of 29 consecutive immunocompetent patients with severe sepsis within 48 hrs of onset were enrolled and underwent laparotomy for a diffuse secondary peritonitis. Thirteen volunteers served as controls. MEASUREMENTS: Blood and peritoneal fluid recovered during laparotomy were analyzed and compared for 1) soluble TNF-alpha, soluble L-selectin, and type I and II TNF-alpha receptor levels; 2) PMN membrane TNF-alpha, membrane L-selectin, and TACE expression (flow cytometry); and 3) TNF-alpha production by cultured PMN. Correlations between these forms of PMN-derived TNF-alpha and the severity of the peritonitis and patient's outcome were investigated. MAIN RESULTS: Elevated soluble TNF-alpha levels in both plasma and peritoneal fluid from the patients were found, together with decreased expression of membrane TNF-alpha and TACE up-regulation at the PMN surface. Soluble L-selectin and type I and II TNF receptors were highly released, suggesting also the role of TACE. In contrast, the capacity of both blood and peritoneal PMN to synthesize TNF-alpha in vitro, in optimal conditions of stimulation (lipopolysaccharide + interferon-gamma), was impaired as compared with controls' blood PMN. Regulation of PMN-derived TNF-alpha was similar in the two compartments, but responses were more pronounced in the peritoneum. TACE up-regulation at the surface of blood-derived PMN correlated with the Sequential Organ Failure Assessment score and vital outcome. CONCLUSION: These human data demonstrate that mTACE is up-regulated at the PMN surface during severe peritonitis. This finding could be related to a paracrine regulatory loop involving some TACE substrates such as TNF-alpha, L-selectin, and TNF receptors.
Assuntos
Metaloendopeptidases/metabolismo , Neutrófilos/metabolismo , Peritonite/imunologia , Sepse/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Proteínas ADAM , Proteína ADAM17 , Biomarcadores , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Selectina L/metabolismo , Masculino , Pessoa de Meia-Idade , Peritônio/metabolismo , Peritonite/complicações , Peritonite/enzimologia , Estudos Prospectivos , Receptores do Fator de Necrose Tumoral/metabolismo , Sepse/complicações , Sepse/enzimologia , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/biossíntese , Regulação para CimaRESUMO
BACKGROUND: Tyrosine protein kinase proteins exert a prominent control on signaling pathways and may couple rapid events, such as action potential and neurotransmitter release, to long-lasting changes in synaptic strength and survival. Whether anesthetics modulate tyrosine kinase activity remains unknown. The aim of the current study was therefore to examine the effects of intravenous and volatile anesthetics on the phosphorylation of focal adhesion kinase (ppFAK), a functionally important nonreceptor tyrosine kinase, in the rat hippocampus. METHODS: Phosphorylation of ppFAK was examined in hippocampal slices by immunoblotting with both antiphosphotyrosine and specific anti-ppFAK antibodies. Experiments were performed in the absence (control) or presence of various concentrations of pharmacologic or anesthetic agents or both. RESULTS: Clinically relevant concentrations of thiopental, propofol, etomidate, isoflurane, sevoflurane, and desflurane induced a concentration-related increase in tyrosine phosphorylation. In contrast, ketamine (up to 100 microm) and the nonimmobilizer F6 (1,2-dichlorohexafluorocyclobutane, 25 microm) did not significantly affect ppFAK phosphorylation. The anesthetic-induced increase in ppFAK phosphorylation was blocked by GF 109203X, RO 318220, and chelerythrin (100 microm), three structurally distinct inhibitors of protein kinase C and U 73122 (50 microm), an inhibitor of phospholipase C. The propofol- and isoflurane-induced increase in ppFAK phosphorylation was reversible and showed nonadditivity of effects with phorbol 12-myristate 13-acetate (an activator of protein kinase C, 0.1 microm). In contrast, ketamine (up to 100 microm), MK801 (10 microm, an N-methyl-d-aspartate receptor antagonist), bicuculline (10 microm, a gamma-aminobutyric acid type A receptor antagonist), and dantrolene (30 microm, an inhibitor of the ryanodine receptor) were ineffective in blocking anesthetic-induced activation of tyrosine phosphorylation. CONCLUSION: Except for ketamine, anesthetic agents markedly increase tyrosine phosphorylation of ppFAK in the rat hippocampus, most likely via the phospholipase C-protein kinase C pathway, whereas the nonimmobilizer F6 does not. These results suggest that ppFAK represents a target for anesthetic action in the brain.
Assuntos
Anestésicos/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Tirosina/metabolismo , Anestésicos Inalatórios/farmacologia , Animais , Relação Dose-Resposta a Droga , Quinase 1 de Adesão Focal , Proteína-Tirosina Quinases de Adesão Focal , Immunoblotting , Técnicas In Vitro , Cinética , Masculino , Fosforilação , Proteína Quinase C/antagonistas & inibidores , Ratos , Acetato de Tetradecanoilforbol/farmacologia , Fosfolipases Tipo C/antagonistas & inibidoresRESUMO
We examined the effect of lidocaine on phosphorylation of the tyrosine kinase focal adhesion kinase (PP125FAK) in rat hippocampal slices by immunoblotting with both antiphosphotyrosine and specific anti-PP125FAK antibodies in the presence of tetrodotoxin (1 microM). Lidocaine induced a concentration-related increase in tyrosine phosphorylation of the 125-kDa band corresponding to PP125FAK phosphorylation (EC50 value=0.39+/-0.09 microM, maximal effect=169+/-28% of control, P<0.001). This effect was sensitive to neither the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK 801, 10 microM) nor the inhibitor of the ryanodine receptor dantrolene (30 microM). In contrast, it was completely blocked by the protein kinase C (PKC) inhibitors chelerythrin, bisindolylmaleimide I (GF 109203X) and bisindolylmaleimide IX (RO-318220, 10 microM). We conclude that lidocaine increases phosphorylation of the tyrosine kinase PP125FAK in the rat hippocampus by a tetrotoxin (TTX)-insensitive mechanism which involves activation of PKC.