RESUMO
BACKGROUND: Excitotoxicity is an important mechanism in secondary neuronal injury after traumatic brain injury (TBI). Excitatory amino acids (EAAs) are increased in cerebrospinal fluid (CSF) in adults after TBI; however, studies in pediatric head trauma are lacking. We hypothesized that CSF glutamate, aspartate, and glycine would be increased after TBI in children and that these increases would be associated with age, child abuse, poor outcome, and cerebral ischemia. METHODS: EAAs were measured in 66 CSF samples from 18 children after severe TBI. Control samples were obtained from 19 children who received lumbar punctures to rule out meningitis. RESULTS: Peak and mean CSF glycine and peak CSF glutamate levels were increased versus control values. Subgroups of patients with TBI were compared by using univariate regression analysis. Massive increases in CSF glutamate were found in children <4 years old and in child abuse victims. Increased CSF glutamate and glycine were associated with poor outcome. A trend toward an association between high glutamate concentration and ischemic blood flow was observed. CONCLUSIONS: CSF EAAs are increased in infants and children with severe TBI. Young age and child abuse were associated with extremely high CSF glutamate concentrations after TBI. A possible role for excitotoxicity after pediatric TBI is supported.
Assuntos
Ácido Aspártico/líquido cefalorraquidiano , Lesões Encefálicas/líquido cefalorraquidiano , Lesões Encefálicas/etiologia , Ventrículos Cerebrais , Maus-Tratos Infantis , Aminoácidos Excitatórios/líquido cefalorraquidiano , Ácido Glutâmico/líquido cefalorraquidiano , Glicina/líquido cefalorraquidiano , Adolescente , Fatores Etários , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/mortalidade , Isquemia Encefálica/etiologia , Estudos de Casos e Controles , Criança , Maus-Tratos Infantis/estatística & dados numéricos , Pré-Escolar , Pessoas com Deficiência/estatística & dados numéricos , Escala de Coma de Glasgow , Escala de Resultado de Glasgow , Humanos , Lactente , Prognóstico , Análise de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: To determine whether bcl-2, a protein that inhibits apoptosis, would be increased in cerebrospinal fluid (CSF) in infants and children after traumatic brain injury (TBI) and to examine the association of bcl-2 concentration with clinical variables. STUDY DESIGN: Bcl-2 was measured in CSF from 23 children (aged 2 months-16 years) with severe TBI and from 19 children without TBI or meningitis (control subjects) by enzyme-linked immunosorbent assay. CSF oligonucleosome concentration was also determined as a marker of DNA degradation. Brain samples from 2 patients undergoing emergent decompressive craniectomies were analyzed for bcl-2 with Western blot and for DNA fragmentation with TUNEL (terminal deoxynucleotidyl-transferase mediated biotin-dUTP nick-end labeling). RESULTS: CSF bcl-2 concentrations were increased in patients with TBI versus control subjects (P =.01). Bcl-2 was increased in patients with TBI who survived versus those who died (P =.02). CSF oligonucleosome concentration tended to be increased after TBI (P =.07) and was not associated with bcl-2. Brain tissue samples showed an increase in bcl-2 in patients with TBI versus adult brain bank control samples and evidence of DNA fragmentation within cells with apoptotic morphology. CONCLUSIONS: Bcl-2 may participate in the regulation of cell death after TBI in infants and children. The increase in bcl-2 seen in patients who survived is consistent with a protective role for this anti-apoptotic protein after TBI.
Assuntos
Apoptose , Lesões Encefálicas/fisiopatologia , Proteínas Proto-Oncogênicas c-bcl-2/líquido cefalorraquidiano , Adolescente , Fatores Etários , Análise de Variância , Lesões Encefálicas/líquido cefalorraquidiano , Lesões Encefálicas/etiologia , Lesões Encefálicas/mortalidade , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Escala de Coma de Glasgow , Humanos , Lactente , Modelos Lineares , Masculino , Análise Multivariada , Nucleossomos/metabolismo , Pennsylvania/epidemiologia , Análise de Sobrevida , Lobo Temporal/metabolismoRESUMO
OBJECTIVES: To describe the etiology, respiratory severity of illness, and outcome in patients with pediatric respiratory failure who were treated with extracorporeal membrane oxygenation (ECMO). To identify predictors of death, and to compare our morbidity and mortality rates with those rates of a previously reported series of patients with pediatric respiratory failure managed conventionally. DESIGN: Survey, case series. SETTING: Intensive care unit in a tertiary care pediatric hospital. PATIENTS: Twenty-eight pediatric patients (3 wks to 20 yrs of age) who underwent ECMO for pediatric respiratory failure between 1985 and 1991. MEASUREMENTS AND MAIN RESULTS: Thirteen (46%) of the 28 patients survived. The most common diagnoses were adult respiratory distress syndrome and nonspecific pneumonitis. Multiple organ system failure occurred in only four (14%) patients; most patients died of respiratory failure. The occurrence of persistent airleak during ECMO was significantly greater in nonsurvivors than in survivors. Furthermore, nonsurvivors had significantly less response to lung reexpansion maneuvers compared with survivors, as measured by a calculated compliance index (effective tidal volume/mean airway pressure x 100). The mortality rate was comparable with those rates of other published studies of conventionally managed and ECMO-treated patients with pediatric respiratory failure. Moreover, our patients appeared to exhibit more severe respiratory failure at the start of ECMO than those patients in other studies. CONCLUSIONS: ECMO appears to be a rational therapy for patients with pediatric respiratory failure who are likely to die with continued conventional management. Recovery of lung function by the end of the first week of ECMO may be a favorable prognostic indicator. Persistent airleak may be a nonfavorable prognostic indicator.
Assuntos
Oxigenação por Membrana Extracorpórea , Insuficiência Respiratória/terapia , Adolescente , Adulto , Barotrauma/etiologia , Criança , Pré-Escolar , Cuidados Críticos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Hemodinâmica , Humanos , Lactente , Recém-Nascido , Avaliação de Resultados em Cuidados de Saúde , Respiração Artificial , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/terapia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Estudos RetrospectivosRESUMO
BACKGROUND AND PURPOSE: Recent evidence suggests a possible role for leukocytes in ischemic brain injury. This study examined the effect of activation of endogenous circulating leukocytes on cerebral blood flow in normal and neutrophil-depleted rats. METHODS: Leukocytes were activated by rapid injection of either 50 micrograms/kg phorbol 12-myristate 13-acetate, a protein kinase C activator, or an equimolar amount of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine, into the right carotid artery. Control rats received an equal volume of dimethyl sulfoxide in saline vehicle. H2-clearance cerebral blood flow was measured in each of the three groups and in vinblastine-treated, neutrophil-depleted rats after carotid artery injection of phorbol. RESULTS: Phorbol 12-myristate 13-acetate dramatically decreased circulating leukocyte and platelet counts from 5 to 120 minutes after infusion and decreased regional cerebral blood flow in the ipsilateral parietal cortex from a baseline of 119 +/- 14 mL.min-1.100 g-1 (mean +/- SEM) to 49 +/- 5 mL.min-1.100 g-1 at 30 minutes (P < .05). Decreased flow persisted for the 2-hour study. Neither N-formyl-methionyl-leucyl-phenylalanine or vehicle had an effect on cerebral blood flow. In the neutrophil-depleted rats the initial decrease in cerebral blood flow at 30 and 60 minutes after infusion of phorbol was observed, but cerebral blood flow was restored to 70% to 80% of its baseline value (P > .05 versus baseline) by 90 to 120 minutes. CONCLUSIONS: The early phorbol 12-myristate 13-acetate-induced decrease in cerebral blood flow may be due to the effects of protein kinase C activation on vascular smooth muscle or on platelet aggregation, whereas the persistent decrease in cerebral blood flow appears to be mediated in part by neutrophil activation.
Assuntos
Circulação Cerebrovascular/efeitos dos fármacos , Neutrófilos/fisiologia , Acetato de Tetradecanoilforbol/farmacologia , Animais , Endotélio Vascular/enzimologia , Ativação Enzimática/efeitos dos fármacos , Masculino , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Contagem de Plaquetas , Proteína Quinase C/metabolismo , Ratos , Ratos Wistar , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fatores de TempoAssuntos
Lesões Encefálicas/fisiopatologia , Isquemia Encefálica/fisiopatologia , Cuidados Críticos , Antioxidantes/uso terapêutico , Fenômenos Bioquímicos , Bioquímica , Lesões Encefálicas/metabolismo , Isquemia Encefálica/metabolismo , Classificação , Cuidados Críticos/métodos , Cuidados Críticos/tendências , Estado Terminal/terapia , Endotélio/fisiologia , Humanos , Imunidade Celular , Inflamação , Leucócitos/fisiologia , Biologia Molecular , Óxido Nítrico , Fisiologia , Espécies Reativas de Oxigênio , Pesquisa/tendênciasAssuntos
Lesões Encefálicas/fisiopatologia , Isquemia Encefálica/fisiopatologia , Parada Cardíaca/complicações , Hipóxia Encefálica/fisiopatologia , Animais , Lesões Encefálicas/patologia , Lesões Encefálicas/terapia , Isquemia Encefálica/etiologia , Isquemia Encefálica/patologia , Isquemia Encefálica/terapia , ATPases Transportadoras de Cálcio , Morte Celular , Ativação do Complemento , Cuidados Críticos , Cães , Humanos , Hipóxia Encefálica/etiologia , Hipóxia Encefálica/patologia , Hipóxia Encefálica/terapia , Inflamação , Peroxidação de Lipídeos , Necrose , Neurônios , ATPase Trocadora de Sódio-PotássioRESUMO
BACKGROUND: The extent to which polymorphonuclear leukocytes and monocytes/macrophages contribute to the pathobiology of cerebral ischemia and stroke is an issue of long-standing contradiction and controversy. Recent developments in the ability to selectively modify leukocyte adhesion with antiadhesion antibodies and the potential clinical application of this therapeutic approach have spurred a resurgence of experimental studies examining the role of leukocytes in cerebral ischemia and stroke. SUMMARY OF REVIEW: We review studies examining leukocyte accumulation, initiation of thrombosis, and exacerbation of ischemic brain injury in stroke, and we examine other proposed contributions of leukocytes to cerebrovascular pathophysiology. CONCLUSIONS: The importance of specific characteristics of a given ischemia model and of underlying stroke risk factors in determining the degree of leukocyte involvement and effectiveness of therapies directed against these cells is discussed.
Assuntos
Isquemia Encefálica/etiologia , Transtornos Cerebrovasculares/etiologia , Macrófagos/fisiologia , Monócitos/patologia , Neutrófilos/patologia , Isquemia Encefálica/terapia , Movimento Celular , Transtornos Cerebrovasculares/patologia , Transtornos Cerebrovasculares/terapia , Humanos , Monócitos/fisiologia , Neutrófilos/fisiologiaRESUMO
In a rat model of complete global brain ischemia (neck tourniquet) lasting either 3 min or 20 min, we monitored global CBF (sagittal sinus H2 clearance) and CMRO2 for 6 h to test the hypothesis that delayed postischemic hyperemia and uncoupling of CBF and CMRO2 occur depending on the severity of the insult. Early postischemic hyperemia occurred in both the 3-min and 20-min groups (p less than 0.05 vs. baseline values) and resolved by 15 min. Hypoperfusion occurred in the 3-min group between 15 and 60 min postischemia (approximately 23% reduction), and in the 20-min group from 15 to 120 min postischemia (approximately 50% reduction) (p less than 0.05), and then resolved. CMRO2 was not significantly different from baseline at any time after ischemia in the 3-min group. After 20 min of ischemia, however, CMRO2 was decreased (approximately 60%) throughout the postischemic period (p less than 0.05). At 5 min after ischemia, CBF/CMRO2 was increased in both groups but returned to baseline from 60 to 120 min postischemia. In the 3-min group, CBF/CMRO2 remained at baseline throughout the rest of the experiment. However, in the 20-min group, CBF/CMRO2 once again increased (approximately 100%), reaching a significant level at 180 min and remaining so for the rest of the 6-h period (p less than 0.05). These data demonstrate biphasic uncoupling of CBF and CMRO2 after severe (20 min) global ischemia in rats. This relatively early reemergence of CBF/CMRO2 uncoupling after 180 min of reperfusion is similar to that observed after prolonged cardiac arrest and resuscitation in humans.
Assuntos
Isquemia Encefálica/fisiopatologia , Encéfalo/metabolismo , Circulação Cerebrovascular/fisiologia , Animais , Encéfalo/fisiopatologia , Isquemia Encefálica/complicações , Isquemia Encefálica/metabolismo , Hiperemia/etiologia , Hiperemia/metabolismo , Masculino , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
At the Children's Hospital of Pittsburgh the extracorporeal membrane oxygenation program was started in 1980. The results of our experience from 1980 to 1985 were previously reported. In the past 2 years 39 additional newborn infants have been treated with this modality, with an overall survival rate of 79% (31/39). This survival rate is much better than that obtained in 33 neonates who had been treated in the previous 5 years (54%; p less than 0.05). A new aspect of our extracorporeal membrane oxygenation program is the use of total apneic lung rest for persisting pulmonary interstitial emphysema during support with the oxygenator. Six neonates were treated with this technique because of worsening pulmonary interstitial emphysema during extracorporeal circulation. Five of them survived. Another indication for extracorporeal membrane oxygenation in our pediatric population has been left ventricular or biventricular failure after cardiopulmonary bypass. Four of our seven patients treated for this indication are long-term survivors. At present, because of the impossibility of using other forms of left ventricular assist devices in the pediatric population, it seems that extracorporeal membrane oxygenation is the most effective treatment for left ventricular failure after cardiopulmonary bypass. From our experience, even in the absence of long-term follow-up of patients supported with extracorporeal membrane oxygenation, it appears that the benefits of this therapeutic modality far exceed the risks in the high-risk population for which it is being used.