Comparison between selective head cooling and whole-body cooling in neonatal therapeutic hypothermia / Comparação entre resfriamento seletivo da cabeça e resfriamento de corpo inteiro na hipotermia terapêutica neonatal

INTRODUCTION: Experimental evidence, as well as improved clinical studies of the reduction of brain injury and, improves the neurological outcome, in newborns with hypoxic-ischemic encephalopathy (HIE) occurring in therapeutic hypothermia (TH). OBJECTIVE: To verify the potential of hypothermic hypoxic-ischemic encephalopathy (HIE) therapy in neonatal asphyxia, based on literature data, comparing the benefits between selective head cooling (SHC) and whole-body cooling (WBC), see that the use of TH as a standard treatment in newborns with moderate or severe HIE has been adopted. METHODS: A search was performed in the PubMed and SciELO databases of human studies, using the keywords "Therapeutic Hypothermia", "Induced Hypothermia", and "Hypoxic-Ischemic Encephalopathy", "Selective cooling of the head", "Total body cooling" and its variables. RESULTS: Eleven articles were selected to compose the review, after detailed reading. There is a consensus, that the reduction of the risk of death or disability at 18 months of life in neonates with moderate to severe HIE, occurs to TH through the techniques of WBC or SHC. It was found in the studies that there is no difference in terms of adverse effects between the two methods. As for radiological changes, such as hypoxic-ischemic injuries and the incidence of seizures after cooling, they are more frequent with SHC. CONCLUSION: Both WBC and SHC demonstrated neuroprotective properties, although WBC provides a broader area of brain protection. However, no significant differences were found between the methods in terms of adverse effects and beneficial short or long-term results.

INTRODUÇÃO: Evidências experimentais, assim como estudos clínicos, sugerem a redução da lesão cerebral e melhora do desfecho neurológico, em recém-nascidos com encefalopatia isquêmica hipóxica (EHI) submetidos à hipotermia terapêutica (HT). OBJETIVO: Verificar a potencialidade da terapia hipotérmica de encefalopatia hipóxico-isquêmica (EHI) na asfixia neonatal, com base em dados da literatura, comparando os benefícios entre o resfriamento seletivo da cabeça (RSC) e o resfriamento de corpo inteiro (RCI), visto que o uso de hipotermia terapêutica (HT) como tratamento padrão em recém-nascidos com EHI moderada ou grave tem sido amplamente adotada. MÉTODOS: Foi realizada uma busca nas bases de dados PubMed e SciELO de estudos em humanos, utilizando-se as palavras-chave "Therapeutic Hypothermia", "Induced Hypothermia", "Hypoxic-Ischemic Encephalopathy", "selective head cooling", "whole body cooling" e suas respectivas variáveis. RESULTADOS: Foram selecionados 11 artigos para compor a revisão, após leitura detalhada. É consenso, a redução do risco de morte ou incapacidade aos 18 meses de vida nos neonatos com EHI moderado a grave, submetidos à HT através das técnicas de RCI ou RSC. Constatou-se diante dos estudos que não há diferença em termos de efeitos adversos entre os dois métodos. Quanto às alterações radiológicas, as lesões hipóxico-isquêmicas e incidência de convulsões após o resfriamento são mais frequentes com o RSC. CONCLUSÃO: Tanto RCI quanto o RSC demonstraram propriedades neuroprotetoras, embora o RCI proporcione uma área de proteção cerebral mais ampla. No entanto, não foram constatadas diferenças significativas entre os métodos quanto a efeitos adversos e a resultados benéficos em curto e longo prazo.

Inserción "velamentosa", encefalopatía hipóxico-isquémica y rehabilitación neurológica: reporte de caso / Velamentous cord insertion, ischemic-hypoxic encephalopathy, and neurological rehabilitation: A case report

Resumen. La encefalopatía hipóxico-isquémica es una causa frecuente e importante de daño neurológico en recién nacidos a término y prematuros. Un evento centinela de esta condición es la vasa previa, específicamente cuando existe anormalidad de la placenta como la inserción "velamentosa" del cordón umbilical. Algunos reportes evidencian la asociación entre estas dos condiciones, pero son escasos los que dan cuenta del proceso de recuperación y del pronóstico neurológico de los niños afectados por ellas. Se presenta el caso de un paciente, con antecedentes de inserción "velamentosa" del cordón umbilical y encefalopatía hipóxico-isquémica, que recibió hipotermia terapéutica (cool cap). Se describe su proceso de rehabilitación neurológica y se calculó el porcentaje de probabilidad de presentar esta condición frente a la población sin estos factores. El niño tenía cinco años y el puntaje en su prueba de Apgar fue de 0 al minuto y de 2 a los 15 minutos. Desarrolló encefalopatía hipóxico-isquémica grave secundaria a una inserción "velamentosa" del cordón umbilical sin diagnóstico prenatal, con gran compromiso neurológico y multisistémico inicial. El proceso de recuperación incluyó el manejo inicial multidisciplinario en la unidad de cuidados intensivos neonatales y el inicio temprano de habilitación neurológica. Hoy el niño está escolarizado y en terapia integral, no presenta deficiencias motoras ni sensoriales en el examen físico, aunque la prueba neuropsicológica sugiere un riesgo de trastorno por déficit de atención e hiperactividad. Habitualmente, los niños con encefalopatía hipóxico-isquémica grave presentan discapacidad por deficiencias motoras, cognitivas o conductuales. El haber recibido hipotermia terapéutica y un manejo estructurado de rehabilitación redujo en gran medida las deficiencias esperadas y ha promovido un satisfactorio desarrollo físico y neurológico.

Abstract. Hypoxic-ischemic encephalopathy is a frequent and important cause of neurological problems in term and preterm newborns. A sentinel event of this entity is the vasa previa, specifically when there is an abnormality of the placenta such as a velamentous cord insertion. Some reports have shown the association between these two entities, but those regarding the recovery process and the neurological prognosis of children with both conditions are scarce. We present the case of a patient with a history of velamentous cord insertion and hypoxic-ischemic encephalopathy who received therapeutic hypothermia (cool cap). We describe his neurological rehabilitation process and we calculated the percentage of probability of presenting this condition compared to the population without these factors. The patient was a five-year-old boy with an Apgar index at birth equal to zero at one minute and equal to two at fifteen minutes who developed severe hypoxic-ischemic encephalopathy secondary to a velamentous cord insertion without prenatal diagnosis and a marked initial neurological and multisystemic compromise. The recovery process included early multidisciplinary management in the neonatal intensive care unit and a focus on early neurological habilitation. The patient is currently in school and he undergoes comprehensive therapies; on physical examination, he presents no motor or sensory deficiencies. His neuropsychological test suggests the risk of attention deficit hyperactivity disorder. Children with severe hypoxic-ischemic encephalopathy usually have disabilities due to motor, cognitive, and/or behavioral deficiencies. Having received therapeutic hypothermia and a structured rehabilitation process greatly reduced the expected deficiencies according to prognosis and have promoted satisfactory physical and neurological development.

Hipotermia terapêutica na encefalopatia hipóxico-isquêmica neonatal: revisão integrativa / Therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy: integrative review / Hipotermia terapéutica em la encefalopatía hipóxico-isquémica neonatal: revisión integrativa

Objetivo: identificar evidências acerca do uso seguro da hipotermia terapêutica em recém-nascidos. Método: revisão integrativa realizada entre junho e julho de 2018, em fontes eletrônicas da Biblioteca Virtual de Saúde e PubMed, por meio da pergunta:"Que evidências podem subsidiar o cuidado de enfermagem voltado para a redução de sequelas em recém-nascidos submetidos à hipotermia terapêutica?".Foram eleitos nove artigos para análise, sendo oito internacionais e um nacional. Resultados:o resfriamento deve acontecer por 72 horas, com hipotermia leve. As indicações para inclusão no protocolo foram: primeiras seis horas de vida, idade gestacional maior que 35 semanas e acidose na primeira hora de vida.São cuidados essenciais: monitoração hemodinâmica, observação da pele, controle térmico retal, vigilância do Eletroencefalograma de Amplitude Integrada. Conclusão: a terapêutica apresenta benefícios, porém sua aplicação depende de protocolo institucional e treinamento das equipes com foco nas potenciais complicações.

Objective: to identify the evidence on safe use of therapeutic hypothermia in newborns. Method: integrative review of the literature, conducted between June and July of 2018, in electronic sources from the Virtual Health Library and PubMed, through the question: "What evidence can support nursing care aimed at reducing sequelae in newborns undergoing therapeutic hypothermia?". Analysis was conducted for nine selected article, being eight from international literature and one from Brazilian national literature. Results: cooling should occur for 72 hours with mild hypothermia. Indications for inclusion in the protocol were: first six hours of life, gestational age greater than 35 weeks and acidosis in the first hour of life. Essential care includes hemodynamic monitoring, skin observation, rectal thermal control, Integrated Amplitude Electroencephalogram surveillance. Conclusion: the therapy has benefits, but its application depends on institutional protocol and team training focusing on potential complications.

Objetivo: identificar la evidencia sobre el uso seguro de la hipotermia terapéutica en recién nacidos. Método: revisión integradora de la literatura, realizada entre junio y julio de 2018, en fuentes electrónicas de la Biblioteca Virtual de Salud y PubMed, a través de la pregunta: "¿Qué evidencia puede apoyar la atención de enfermería dirigida a reducir las secuelas en los recién nacidos que sufren hipotermia terapéutica?". Se realizaron análisis para nueve artículos seleccionados, ocho de literatura internacional y uno de literatura nacional brasileña. Resultados: el enfriamiento debe ocurrir durante 72 horas con hipotermia leve. Las indicaciones para la inclusión en el protocolo fueron: primeras seis horas de vida, edad gestacional mayor de 35 semanas y acidosis en la primera hora de vida. El cuidado esencial incluye monitoreo hemodinámico, observación de la piel, control térmico rectal, vigilancia integrada de electroencefalograma de amplitud. Conclusión: la terapia tiene beneficios, pero su aplicación depende del protocolo institucional y del entrenamiento del equipo, enfocándose en posibles complicaciones.

Selective head cooling and whole body cooling as neuroprotective agents in severe perinatal asphyxia

SUMMARY INTRODUCTION The possibility that hypothermia has a therapeutic role during or after resuscitation from severe perinatal asphyxia has been a longstanding focus of research. Studies designed around this fact have shown that moderate cerebral hypothermia, initiated as early as possible, has been associated with potent, long-lasting neuroprotection in perinatal patients. OBJECTIVES To review the benefits of hypothermia in improving cellular function, based on the cellular characteristics of hypoxic-ischemic cerebral injury and compare the results of two different methods of cooling the brain parenchyma. METHODS Medline, Lilacs, Scielo, and PubMed were searched for articles registered between 1990 and 2019 in Portuguese and English, focused on trials comparing the safety and effectiveness of total body cooling with selective head cooling with HIE. RESULTS We found that full-body cooling provides homogenous cooling to all brain structures, including the peripheral and central regions of the brain. Selective head cooling provides a more extensive cooling to the cortical region of the brain than to the central structures. CONCLUSIONS Both methods demonstrated to have neuroprotective properties, although full-body cooling provides a broader area of protection. Recently, head cooling combined with some body cooling has been applied, which is the most promising approach. The challenge for the future is to find ways of improving the effectiveness of the treatment.

RESUMO INTRODUÇÃO A possibilidade de a hipotermia ter um papel terapêutico durante ou após a reanimação da asfixia perinatal grave tem sido um foco de pesquisa de longa data. Estudos desenhados em torno desse fato mostraram que a hipotermia cerebral moderada, iniciada o mais cedo possível, tem sido associada à neuroproteção potente e duradoura em espécies perinatais. OBJETIVOS Resumidamente, analisar os benefícios da hipotermia na melhoria da função celular, com base nas características celulares da lesão cerebral hipóxico-isquêmica e comparar os resultados de dois métodos diferentes de resfriamento do parênquima cerebral. MATERIAL E MÉTODOS Medline, Lilacs, SciELO e PubMed foram pesquisados para artigos registrados entre 1990 e 2019 nos idiomas português e inglês, com foco em estudos comparando segurança e eficácia do resfriamento corporal total com o resfriamento seletivo da cabeça com EHI. RESULTADOS Descobrimos que o resfriamento de corpo inteiro fornece resfriamento homogêneo para todas as estruturas cerebrais, incluindo as regiões periférica e central do cérebro. O resfriamento seletivo da cabeça fornece um resfriamento mais amplo para a região cortical do cérebro do que para as estruturas centrais. CONCLUSÕES Ambos os métodos demonstraram ter propriedades neuroprotetoras, embora o resfriamento de corpo inteiro forneça uma área mais ampla de proteção. Recentemente, o resfriamento da cabeça combinado com algum resfriamento corporal foi aplicado e essa é a maneira mais promissora. O desafio para o futuro é encontrar formas de melhorar a eficácia do tratamento.

Hallazgos ecográficos transfontanelar como pronóstico de alteraciones motoras a los dos años en neonatos con encefalopatía hipóxico-isquémica / Transfontanelar echographic findings as a prognosis of motor alterations at two years in neonatos with hipoxico-isquemica

Objetivo: Determinar si las alteraciones en la ecografía transfontanelar es factor pronóstico para alteraciones del desarrollo motor durante los 2 primeros años de vida en neonatos a término diagnosticados con Encefalopatía Hipóxico-Isquémica, atendidos en el Hospital Regional Docente Las Mercedes y el Hospital Nacional Almanzor Aguinaga Asenjo, durante el periodo 2015-2017. Material y métodos: estudio analítico, que se incluyeron 43 infantes con el antecedente de Encefalopatía Hipóxico-Isquémica que contaban con ecografía transfontanelar tomada en los primeros 7 días de vida, de quiénes se recolectó información mediante historias clínicas y entrevistas. Se evaluó el desarrollo motor grueso a los 2 años de edad mediante el test de "Sistema de Evaluación de la Función Motriz Gruesa". Resultados: De los 43 participantes, 29 (65,12%) presentaron alteraciones ecográficas y 14 (32,56%), tuvieron alteraciones motoras. De los 14 participantes que tuvieron alteración de la función motriz gruesa, la hemorragia intraventricular y el edema cerebral fueron las más frecuentes, afectando cada una a 6 infantes (42,9%). La relación entre ambas variables (hallazgos ecográficos y alteraciones motoras gruesas) fue significativamente estadística (IC 95%, p<0,05). Conclusión: Las alteraciones en la ecografía transfontanelar son factor pronóstico para déficit en el desarrollo motor grueso durante los 2 primeros años de vida en neonatos a término con diagnóstico de Encefalopatía Hipóxico Isquémica.(AU)

Objetive: Determine if the alterations in the transfontanelar ultrasound is a prognostic factor for motor development alterations during the first 2 years of life in term infants diagnosed with Hypoxic-Ischemic Encephalopathy, seen at the Las Mercedes Regional Hospital and the Almanzor Aguinaga National Hospital Asenjo, during the period 2015-2017. Material and methods: Analytical study, which included 43 infants with a history of Hypoxic-Ischemic Encephalopathy who had transfontanel ultrasound taken in the first 7 days of life, from whom information was collected through clinical histories and interviews. The gross motor development at 2 years of age was evaluated by means of the "Thick Motor Function Assessment System" test. Results: Of the 43 participants, 29 (65.12%) presented ultrasonographic alterations and 14 (32.56%) had motor alterations. Of the 14 participants who had impaired gross motor function, intraventricular hemorrhage and cerebral edema were the most frequent, each affecting 6 infants (42.9%). The relationship between both variables (echographic findings and gross motor alterations) was statistically significant (95% CI, p <0.05). Conclusion: Alterations in transfontanel ultrasound are a prognostic factor for deficit in gross motor development during the first 2 years of life in term neonates with a diagnosis of Ischemic Hypoxic Encephalopathy.(AU)

Effects of hyperbaric oxygen and nerve growth factor on the long-term neural behavior of neonatal rats with hypoxic ischemic brain damage

Abstract Purpose: To evaluate the effects of HBO (Hyperbaric oxygen) and NGF (Nerve growth factor) on the long-term neural behavior of neonatal rats with HIBD (Neonatal hypoxic ischemic brain damage). Methods: The HIBD model was produced by ligating the right common carotid artery of 7 days old SD (Sprague-Dawley) rats followed by 8% O2 + 92% N2 for 2h. Totally 40 rats were randomly divided into 5 groups including sham-operated group, HIBD control group, HBO treated group, NGF treated group and NGF + HBO treated group. The learning and memory ability of these rats was evaluated by Morris water maze at 30 days after birth, and sensory motor function was assessed by experiments of foot error and limb placement at 42 days after birth. Results: The escape latency of HBO treated group, NGF treated group and NGF + HBO treated group was shorter than that of HIBD control group (p<0.01) and longer than that of sham-operated group. The piercing indexes of 3 treated groups were higher than that of HIBD control group (p<0.01). Conclusion: Hyperbaric oxygen and nerve growth factor treatments may improve learning and memory ability and sensory motor function in neonatal rats after hypoxic ischemic brain damage.

Effects of hyperbaric oxygen and nerve growth factor on the long-term neural behavior of neonatal rats with hypoxic ischemic brain damage

Purpose: To evaluate the effects of HBO (Hyperbaric oxygen) and NGF (Nerve growth factor) on the long-term neural behavior of neonatal rats with HIBD (Neonatal hypoxic ischemic brain damage). Methods: The HIBD model was produced by ligating the right common carotid artery of 7 days old SD (Sprague-Dawley) rats followed by 8% O2 + 92% N2 for 2h. Totally 40 rats were randomly divided into 5 groups including sham-operated group, HIBD control group, HBO treated group, NGF treated group and NGF + HBO treated group. The learning and memory ability of these rats was evaluated by Morris water maze at 30 days after birth, and sensory motor function was assessed by experiments of foot error and limb placement at 42 days after birth. Results: The escape latency of HBO treated group, NGF treated group and NGF + HBO treated group was shorter than that of HIBD control group (p 0.01) and longer than that of sham-operated group. The piercing indexes of 3 treated groups were higher than that of HIBD control group (p 0.01). Conclusion: Hyperbaric oxygen and nerve growth factor treatments may improve learning and memory ability and sensory motor function in neonatal rats after hypoxic ischemic brain damage.(AU)

Influência da hipotermia terapêutica no desenvolvimento motor de recém-nascidos com encefalopatia hipóxico-isquêmica / Therapeutic hypothermia influence on the motor development of infants with hypoxic-ischemic encephalopathy

OBJETIVO: Avaliar a influência da hipotermia no desenvolvimento motor de recém-nascidos com encefalopatia hipóxico--isquêmica. MÉTODOS: Foi realizada pesquisa nas bases de dados LILACS, MEDLINE, SciELO, Bireme e PubMed, em português, inglês e espanhol. RESULTADOS: A encefalopatia hipóxico-isquêmica é uma das principais causas de morte neonatal e de deficiência a longo prazo. Todos os estudos utilizaram a hipotermia leve, e os critérios para inclusão de recém-nascidos com encefalopatia hipóxico-isquêmica não se diferenciaram entre si. A redução de taxa de mortalidade foi de 15%, e houve redução de deficiências a longo prazo. CONCLUSÃO: A técnica foi eficaz e segura, quando iniciada no prazo de 6 horas após o nascimento em crianças a termo. Ela reduziu a taxas de mortalidade e melhorou da gravidade neurológica, reduzindo a presença de deficiência motora e cognitiva na infância. São de grande importância a intervenção precoce e o acompanhamento do desenvolvimento.

OBJECTIVE: To evaluate the influence of hypothermia on motor development of infants with hypoxic-ischemic encephalopathy. METHODS: Research was conducted in the databases LILACS, MEDLINE, SciELO, Bireme and PubMed, in Portuguese, English and Spanish. RESULTS: Hypoxic-ischemic encephalopathy is a major cause of neonatal death and the presence of long-term disability. All studies used mild hypothermia, and the criteria for inclusion of newborns with hypoxic-ischemic encephalopathy did not differ among themselves. The reduction of mortality rate was 15%, and decreased long-term disabilities. CONCLUSION: The technique was safe and effective when started within 6 hours after birth in full-term infants. She has reduced mortality rates and improved neurological severity of, reducing the presence of motor and cognitive impairment in children. They are of great importance to early intervention and monitoring of development

Hipotermia terapêutica após parada cardíaca: preditores de prognóstico / Therapeutic hypothermia after cardiac arrest: outcome predictors

Resumo Objetivo: A determinação do prognóstico de pacientes em coma após parada cardíaca tem implicações clínicas, éticas e sociais. Exame neurológico, marcadores de imagem e bioquímicos são ferramentas úteis e bem aceitas na previsão da recuperação. Com o advento da hipotermia terapêutica, tais informações devem de ser confirmadas. Neste estudo procurou-se determinar a validade de diferentes marcadores que podem ser utilizados na detecção de pacientes com mau prognóstico durante um protocolo de hipotermia. Métodos: Foram coletados prospectivamente os dados de pacientes adultos, internados após parada cardíaca em nossa unidade de terapia intensiva para realização de protocolo de hipotermia. Nosso intuito foi realizar um estudo descritivo e analítico para analisar a relação entre os dados clínicos, parâmetros neurofisiológicos, de imagem e bioquímicos, e o desfecho após 6 meses, conforme definido pela escala Cerebral Performance Categories (bom, se 1-2, e mau, se 3-5). Foi coletada uma amostra para determinação de neuroenolase após 72 horas. Os exames de imagem e neurofisiológicos foram realizados 24 horas após o período de reaquecimento. Resultados: Foram incluídos 67 pacientes, dos quais 12 tiveram evolução neurológica favorável. Fibrilação ventricular e atividade teta no eletroencefalograma se associaram a bom prognóstico. Pacientes submetidos a resfriamento mais rápido (tempo médio de 163 versus 312 minutos), com lesão cerebral causada por hipóxia/isquemia detectada na ressonância nuclear magnética ou níveis de neuroenolase superiores a 58ng/mL se associaram a desfecho neurológico desfavorável (p < 0,05). Conclusão: A presença de lesão cerebral causada por hipóxia/isquemia e de neuroenolase foram fortes preditores de má evolução neurológica. Apesar da crença de que atingir rapidamente a temperatura alvo da hipotermia melhora o prognóstico neurológico, nosso estudo demonstrou que este fator se associou a um aumento da mortalidade e a uma pior evolução neurológica.

ABSTRACT Objective: The determination of coma patient prognosis after cardiac arrest has clinical, ethical and social implications. Neurological examination, imaging and biochemical markers are helpful tools accepted as reliable in predicting recovery. With the advent of therapeutic hypothermia, these data need to be reconfirmed. In this study, we attempted to determine the validity of different markers, which can be used in the detection of patients with poor prognosis under hypothermia. Methods: Data from adult patients admitted to our intensive care unit for a hypothermia protocol after cardiac arrest were recorded prospectively to generate a descriptive and analytical study analyzing the relationship between clinical, neurophysiological, imaging and biochemical parameters with 6-month outcomes defined according to the Cerebral Performance Categories scale (good 1-2, poor 3-5). Neuron-specific enolase was collected at 72 hours. Imaging and neurophysiologic exams were carried out in the 24 hours after the rewarming period. Results: Sixty-seven patients were included in the study, of which 12 had good neurological outcomes. Ventricular fibrillation and electroencephalographic theta activity were associated with increased likelihood of survival and improved neurological outcomes. Patients who had more rapid cooling (mean time of 163 versus 312 minutes), hypoxic-ischemic brain injury on magnetic resonance imaging or neuron-specific enolase > 58ng/mL had poor neurological outcomes (p < 0.05). Conclusion: Hypoxic-ischemic brain injury on magnetic resonance imaging and neuron-specific enolase were strong predictors of poor neurological outcomes. Although there is the belief that early achievement of target temperature improves neurological prognoses, in our study, there were increased mortality and worse neurological outcomes with earlier target-temperature achievement.

Translational realistic expectations of chronic cerebral hypoxemia in rat model after bilateral commom carotid artery ligation. Neurocognitive aspects

To evaluate the effects of chronic cerebral hypoxia on memory of rats submitted to bilateral common carotid artery ligation (BCCL). METHODS: Every each week, for 16 weeks, 31 rats were tested for memory using a water and land mazes and compared with 30 normal rats (control group A). The variables were expressed by their mean and standard error of the mean (SEM). p<0.05 was used for rejecting the null hypothesis. The study was approved by the Ethics Committee for animal investigation. RESULTS: There was a significant increase in the latency time, in the survival water and land mazes, after four weeks (study group B) follow-up. However, without any medication or therapeutically induced measures, after 16 weeks (study group C) follow-up the latency mean times tend to be similar to control group (A) in the neurocognitive tests. CONCLUSIONS: Neurocognitive deficits after 16 weeks post-operative follow-up of rats that underwent bilateral common carotid artery ligation is a natural adaptive phenomenon. Thus, is not realistic to allow translational information from this animal model for therapeutically approaches aiming at to prevent, or to improve brain damage in human beings suffering from chronic deprivation of adequate blood supply.

Translational realistic expectations of chronic cerebral hypoxemia in rat model after bilateral commom carotid artery ligation. Neurocognitive aspects

To evaluate the effects of chronic cerebral hypoxia on memory of rats submitted to bilateral common carotid artery ligation (BCCL). METHODS: Every each week, for 16 weeks, 31 rats were tested for memory using a water and land mazes and compared with 30 normal rats (control group A). The variables were expressed by their mean and standard error of the mean (SEM). p<0.05 was used for rejecting the null hypothesis. The study was approved by the Ethics Committee for animal investigation. RESULTS: There was a significant increase in the latency time, in the survival water and land mazes, after four weeks (study group B) follow-up. However, without any medication or therapeutically induced measures, after 16 weeks (study group C) follow-up the latency mean times tend to be similar to control group (A) in the neurocognitive tests. CONCLUSIONS: Neurocognitive deficits after 16 weeks post-operative follow-up of rats that underwent bilateral common carotid artery ligation is a natural adaptive phenomenon. Thus, is not realistic to allow translational information from this animal model for therapeutically approaches aiming at to prevent, or to improve brain damage in human beings suffering from chronic deprivation of adequate blood supply.(AU)

Hiperoxia por dos horas produce daño morfológico cerebral luego de asfixia neonatal experimental / Two-hour hyperoxia following experimental neonatal asphyxia produces morphological brain damage

Objetivos: Determinar el efecto de una exposición de dos horas de hiperoxia al 21%, 40% y 100% sobre la morfología cerebral, en un modelo experimental de asfixia neonatal. Diseño: Estudio experimental. Institución: Instituto Nacional de Salud del Niño, Lima, Perú. Material biológico: Ratas albinas Holtzmann. Intervenciones: Ciento veinte ratas albinas Holtzmann de una semana de nacidas (a excepción del grupo control) fueron sometidas a asfixia experimental por ligadura de la arteria carótida izquierda y luego expuestas a hipoxia (oxígeno al 8%). Después fueron asignadas aleatoriamente a uno de los siguientes grupos: exposición por dos horas a O2 al 100%, a O2 al 40%, a O2 al 21% y un grupo control (no expuesto a asfixia experimental). El daño cerebral fue evaluado mediante la medición del peso cerebral y el porcentaje del área cerebral con daño microscópico. Principales medidas de resultados: Daño cerebral. Resultados: El peso cerebral promedio fue menor en los animales de los grupos sometidos a hiperoxia experimental (ANOVA; p<0,001). Se presentó daño cerebral microscópico con mayor frecuencia en el grupo sometido a hipoxia experimental que recibió O2 100% por dos horas y con menor frecuencia en el que recibió O2 al 40% (60% versus 43,3%), diferencia que fue estadísticamente significativa (prueba χ²; p<0,001). El grupo sometido a hipoxia experimental que recibió O2 100% tuvo un mayor porcentaje promedio de área cerebral con daño microscópico (18,3%), en comparación con los otros grupos de hipoxia experimental, aunque la diferencia no fue estadísticamente significativa (ANOVA; p=0,123). Conclusiones: La hiperoxia al 100% por dos horas se asoció con menor peso cerebral y mayor daño cerebral en animales de experimentación sometidos a asfixia neonatal experimental.

Objectives: To determine the effect of 2-hour exposure to 21% O2, 40% O2 and 100% O2 on cerebral morphology in an experimental model of neonatal asphyxia. Design: Experimental study. Setting: Instituto Nacional de Salud del Niño, Lima, Peru. Biologic material: Holtzman albino rats. Interventions: A sample of 120 one week-old Holtzman albino rats (with the exception of the control group) underwent experimental asphyxia by left carotid artery ligation and then exposition to hypoxia (8% O2); thereafter rats were randomly assigned to one of the following groups: exposition for two hours to 100% O2, to 40% O2, to 21% O2, and a control group (not exposed to experimental asphyxia). Brain damage was determined by brain weight and percentage of microscopic brain area damage. Main outcome measures: Brain damage. Results: Brain weight was lower in animals with experimental hyperoxia (ANOVA, p<0.001). Microscopic damage was more frequent in the group receiving 100% O2 for two hours and with less frequency in the group receiving 40% O2 (60% versus 43.3%). The difference was statistically significant (χ2 test: p<0.001). The group receiving 100% O2 had more microscopic brain damage (18.3 %) in comparison with the other groups of experimental hypoxia, but the difference was not statistically significant (ANOVA, p=0.123). Conclusions: Following neonatal asphyxia 100% two-hour hyperoxia was associated with less brain weight and more damage in experimental animals.

Autogenous fecal peritonitis in Wistar rats with permanent bilateral carotid occlusion: morbidity, mortality and microbiological response

PURPOSE: To investigate morbidity, mortality and microbiological response to fecal peritonitis induced in Wistar rats with permanent bilateral carotid ligation (PBCL). METHODS: Fecal peritonitis was induced in 30 rats, with 10 animals in each group: Group1 - normal young animals; Group2 - normal mature animals; and Group3 - rats with PBCL after four months postoperative follow-up. Peritonitis was induced with 10% stool suspension. Morbidity and mortality were evaluated. The survival animals after seven days were euthanized for tests. For microbiological studies blood were collected from the carotids and right ventricle; and fragments of lung and peritoneum. RESULTS: The morbidity and mortality of young animals were significantly lower than in mature animals with and without PBCL. There was no difference in morbidity and mortality among mature rats with and without PBCL. The diversity of microorganisms producing septicemia was similar to native micro biota of the large bowel. CONCLUSIONS: The immune response was more efficient in young animals, represented by significant less morbidity and no natural mortality. PBLC did not affect morbidity and mortality in mature rats. The immune response to fecal peritonitis has age as an independent predictor.

Learning and survival memory undergoing a permanent bilateral carotid ligation in rats

PURPOSE: To evaluate the effect of cerebral hypoxia-ischemia on memory and learning survival of rats submitted to permanent bilateral carotid ligation (PBCL). METHODS: Twenty-four survivors of PBCL were evaluated after 30 days with regard to memory and learning using a water survival maze. Twenty-three healthy rats were used as control group. The results were expressed by their means and standard error of the mean (SEM). p<0.05 was used for rejecting the null hypothesis. The study was approved by the Ethics Committee for animal investigation. RESULTS: The mortality rate for the surgery was 44.4%. The latency time to find the survival platform was higher in rats that underwent PBCL (Normal: 10.24 ± 1.85s - Study: 25.30 ± 4.69s - Mann - Whitney p=0.0388). Additionally, the type of swimming and the spatial stability of the studied rats on the survival platform were compromised in these animals. CONCLUSION: The permanent bilateral carotid ligation induces change in the learning and survival memory.

Autogenous fecal peritonitis in Wistar rats with permanent bilateral carotid occlusion: morbidity, mortality and microbiological response

PURPOSE: To investigate morbidity, mortality and microbiological response to fecal peritonitis induced in Wistar rats with permanent bilateral carotid ligation (PBCL). METHODS: Fecal peritonitis was induced in 30 rats, with 10 animals in each group: Group1 - normal young animals; Group2 - normal mature animals; and Group3 - rats with PBCL after four months postoperative follow-up. Peritonitis was induced with 10% stool suspension. Morbidity and mortality were evaluated. The survival animals after seven days were euthanized for tests. For microbiological studies blood were collected from the carotids and right ventricle; and fragments of lung and peritoneum. RESULTS: The morbidity and mortality of young animals were significantly lower than in mature animals with and without PBCL. There was no difference in morbidity and mortality among mature rats with and without PBCL. The diversity of microorganisms producing septicemia was similar to native micro biota of the large bowel. CONCLUSIONS: The immune response was more efficient in young animals, represented by significant less morbidity and no natural mortality. PBLC did not affect morbidity and mortality in mature rats. The immune response to fecal peritonitis has age as an independent predictor.(AU)

Learning and survival memory undergoing a permanent bilateral carotid ligation in rats

PURPOSE: To evaluate the effect of cerebral hypoxia-ischemia on memory and learning survival of rats submitted to permanent bilateral carotid ligation (PBCL). METHODS: Twenty-four survivors of PBCL were evaluated after 30 days with regard to memory and learning using a water survival maze. Twenty-three healthy rats were used as control group. The results were expressed by their means and standard error of the mean (SEM). p<0.05 was used for rejecting the null hypothesis. The study was approved by the Ethics Committee for animal investigation. RESULTS: The mortality rate for the surgery was 44.4%. The latency time to find the survival platform was higher in rats that underwent PBCL (Normal: 10.24 ± 1.85s - Study: 25.30 ± 4.69s - Mann - Whitney p=0.0388). Additionally, the type of swimming and the spatial stability of the studied rats on the survival platform were compromised in these animals. CONCLUSION: The permanent bilateral carotid ligation induces change in the learning and survival memory.(AU)