Ventilation-induced changes correlate to pulmonary vascular response and VEGF, VEGFR-1/2, and eNOS expression in the rat model of postnatal hypoxia

Neonatal asphyxia occurs due to reduction in oxygen supply to vital organs in the newborn. Rapid restoration of oxygen to the lungs after a long period of asphyxia can cause lung injury and decline of respiratory function, which result from the activity of molecules that induce vascular changes in the lung such as nitric oxide (NO) and vascular endothelial growth factors (VEGF). In this study, we evaluated the pulmonary and vascular morphometry of rats submitted to the model of neonatal asphyxia and mechanical ventilation, their expression of pulmonary VEGF, VEGF receptors (VEGFR-1/VEGFR-2), and endothelial NO synthase (eNOS). Neonate Sprague-Dawley rats (CEUA #043/2011) were divided into four groups (n=8 each): control (C), control submitted to ventilation (CV), hypoxia (H), and hypoxia submitted to ventilation (HV). The fetuses were harvested at 21.5 days of gestation. The morphometric variables measured were body weight (BW), total lung weight (TLW), left lung weight (LLW), and TLW/BW ratio. Pulmonary vascular measurements, VEGFR-1, VEGFR-2, VEGF, and eNOS immunohistochemistry were performed. The morphometric analysis showed decreased TLW and TLW/BW ratio in HV compared to C and H (P<0.005). Immunohistochemistry showed increased VEGFR-2/VEGF and decreased VEGFR-1 expression in H (P<0.05) and lower eNOS expression in H and HV. Median wall thickness was increased in H, and the expression of VEGFR-1, VEGFR-2, VEGF, and eNOS was altered, especially in neonates undergoing H and HV. These data suggested the occurrence of arteriolar wall changes mediated by NO and VEGF signaling in neonatal hypoxia.

Brain caspase-3 and intestinal FABP responses in preterm and term rats submitted to birth asphyxia

Neonatal asphyxia can cause irreversible injury of multiple organs resulting in hypoxic-ischemic encephalopathy and necrotizing enterocolitis (NEC). This injury is dependent on time, severity, and gestational age, once the preterm babies need ventilator support. Our aim was to assess the different brain and intestinal effects of ischemia and reperfusion in neonate rats after birth anoxia and mechanical ventilation. Preterm and term neonates were divided into 8 subgroups (n=12/group): 1) preterm control (PTC), 2) preterm ventilated (PTV), 3) preterm asphyxiated (PTA), 4) preterm asphyxiated and ventilated (PTAV), 5) term control (TC), 6) term ventilated (TV), 7) term asphyxiated (TA), and 8) term asphyxiated and ventilated (TAV). We measured body, brain, and intestine weights and respective ratios [(BW), (BrW), (IW), (BrW/BW) and (IW/BW)]. Histology analysis and damage grading were performed in the brain (cortex/hippocampus) and intestine (jejunum/ileum) tissues, as well as immunohistochemistry analysis for caspase-3 and intestinal fatty acid-binding protein (I-FABP). IW was lower in the TA than in the other terms (P<0.05), and the IW/BW ratio was lower in the TA than in the TAV (P<0.005). PTA, PTAV and TA presented high levels of brain damage. In histological intestinal analysis, PTAV and TAV had higher scores than the other groups. Caspase-3 was higher in PTAV (cortex) and TA (cortex/hippocampus) (P<0.005). I-FABP was higher in PTAV (P<0.005) and TA (ileum) (P<0.05). I-FABP expression was increased in PTAV subgroup (P<0.0001). Brain and intestinal responses in neonatal rats caused by neonatal asphyxia, with or without mechanical ventilation, varied with gestational age, with increased expression of caspase-3 and I-FABP biomarkers.

The value of brainstem evoked potential in clinical decision of a patient with hypoxic-ischemic encephalopathy

Establishing a prognosis for hypoxic-ischemic encephalopathy during the neonatal period is extremely difficult, as the neuroplasticity of the developing brain makes it almost impossible to measure the affected area. This case report describes a newborn with severe perinatal asphyxia and neonatal neurological syndrome including absent suck reflex. Normal brainstem auditory evoked potential led the diagnosis towards a transitory dysfunction of deglutition, and the subject received daily stimulation in the hospital environment. Suck developed satisfactorily by day of life 30 and the patient was released without having to be tube fed. Neurophysiologic tests can be of value in the clinical decisions and analysis of functional prognosis of patients with hypoxic-ischemic encephalopathy.

Estabelecer o prognóstico da encefalopatia hipóxico-isquêmica durante o período neonatal é extremamente difícil, devido à neuroplasticidade do cérebro em desenvolvimento que impede a medida exata das áreas afetadas. Este relato descreve um recém-nascido a termo com grave asfixia perinatal e síndrome neurológica pós-natal, incluindo ausência do reflexo de sucção. O potencial evocado auditivo do tronco cerebral foi normal, sugerindo o diagnóstico de disfunção transitória da deglutição. Após estimulação diária no hospital a sucção foi obtida satisfatoriamente, e o paciente recebeu alta sem necessidade de alimentação enteral. Os testes neurofisiológicos podem ser de grande valor em decisões clínicas e análise funcional prognóstica de pacientes com encefalopatia hipóxico-isquêmica.

Asfixia perinatal e problemas Cardíacos / Perinatal asphyxia and heart problems

Objetivo - Avaliar a gravidade das complicações cardíacas na asfixia neonatal, sua evolução e correlacioná-las com o grau e duração do processo hipóxico. Métodos - Foram estudados 90 bebês nos últimos 7 anos com grau de Apgar = 6 no 5§ min de vida. Pelo protocolo, após o exame físico e os cuidados intensivos, eram submetidos a dosagem do pH arterial, CPK-MB, DHL, glicemia, além da realização de radiografia de tórax, eletrocardiograma (ECG), ecocardiograma, seriados e repetidos a cada semana. Aqueles que faleceram eram levados à necropsia. Resultados - Dos 90, 73 (81 por cento) eram prematuros, 30 (41 por cento) eram apropriados para a idade gestacional (AIG) e 43 (59 por cento) eram pequenos (PIG). Em 21 (23 por cento) casos havia pH arterial < 7,2. Os quadros clínicos mais observados foram: pneumonia em 28 (31 por cento), anemia 24 (26 por cento) e icterícia moderada 12 (5 por cento), entre outros. Ao exames físico observaram-se sopro sistólico em 46 (50 por cento), ictus propulsivo 18 (20 por cento) e ICC em 8 (9 por cento). No ECG, os sinais mais freqüentes foram alterações de repolarização (ST e T) em 44 (49 por cento). No ecocardiograma, observou-se persistência do canal arterial (PCA) em 20 (22 por cento), regurgitação tricúspide em 6 (7 por cento), hipertensão pulmonar em 6 (8 por cento), hipocontratilidade de VE e dilatação de VD em 4 (5 por cento). Dos 23 óbitos, 14 foram estudados e as alterações mais freqüentes foram necrose e de fibras em 8 (68 por cento) casos e em 4 (29 por cento) congestão, vacuolização e perda de estriação. Conclusão - A maioria teve evolução favorável mesmo naqueles que tiveram acidemia importante. Muitas alterações de ECG e ecocardiograma se normalizaram. Daqueles que evoluiram para óbito, as lesões mais graves ocorreram nos que sofreram, por mais tempo, processo anóxico.

Myocardial changes in neonates dying of asphyxia neonatorum.

Ten neonates, asphyxiated at birth, were studied by Apgar score, ECG ischaemic score grading (ECGisg), Cardiothoracic (CT) ratio, biochemical parameters like CPK, CPK-MB fraction during life; and they were subjected to postmortem study with particular attention to the changes in the heart. The study revealed that 7 out of 10 asphyxiated neonates showed variable evidences of myocardial damage; but the extent of damage though well correlated with biochemical parameters, did not correspond well with the extent of asphyxia and the survival period. In rest 3 cases, myocardial damage was not overt though there was evidence of asphyxia and evidence of myocardial damage in the form of elevated CPK-MB level. These patients probably had died of "Biochemical Lesion" as described by Rudolf Peter.