Christina Kohlhauser

Histological changes and neurotransmitter levels three months following perinatal asphyxia in the rat

The involvement of excitatory amino acids (EAA) in the pathogenesis of hypoxic-ischemic states is well-documented. Information on the role of overexcitation by EAA in perinatalasphyxia (PA), however, is limited and data from adult models cannot be directly extrapolated to immature systems. Moreover, most adult models of ischemia are representing stroke rather than PA. We decided to study long term effects in a non-invasive rat model of PA resembling the clinical situation three months following the asphyctic insult. Morphometry on Nissl - stained sections was used to determine neuronal death in frontal cortex, striatum, hippocampus CA1, hypothalamus and cerebellum L1, and the amino acids glutamate, glutamine, aspartate, GABA, taurine, arginine as well as histamine, serotonin and 5-hydroxy-indoleacetic acid were determined in several brain regions and areas. Morphometry revealed that neuronal loss was present in the hippocampal area CA1 in all groups with PA and that morphological alterations were significantly higher in the cerebellar granular layer. The prominent light microscopical finding in all areas of asphyctic rats studied was decreased Nissl-staining, suggesting decreased cellular RNA levels. Glutamate, aspartate and glutamine were significantly elevated in the hypothalamus of asphyctic rats probably indicating overstimulation by EAA. Excitotoxicity in this area would be compatible with findings of emotional / behavioral deficits observed in a parallel study in our model of PA. Our observations point to and may help to explain behavioral and emotional deficits in Man with a history of perinatal asphyxia.

Energy metabolism in graded perinatal asphyxia of the rat

Although information on energy metabolism during hypoxemic-ischemic states is abundant, data on perinatal asphyxia (PA) are limited. As results from hypoxia-ischemia cannot be directly extrapolated to PA, a clinical entity characterized by acidosis, hypoxemia and hypercapnia, we decided to use a rat model of graded PA during delivery. Cesarean section was performed at the 21st day of gestation and the pups, still in the uterus horns, were asphyxiated from 0 to 20 minutes. In this model survival decreases with the length of asphyxia. Early changes of energy-rich phosphates in brain, heart and kidney were determined by HPLC. ATP and phosphocreatine gradually decreased with the length of asphyxia, with highest ATP depletion rate occurring in the kidney. ATP: brain 1.39 +/- 0.71 (0 min) to 0.06 microM/g wwt (20 min); heart 4.73 +/- 0.34 (0 min) to 1.08 +/- 0.47 (20 min); kidney 1.62 +/- 0.11 (0 min) to 0.02 +/- 0.02 (20 min). Phosphocreatine: brain 1.65 +/- 0.68 (0 min) to 0.51 +/- 0.45 microM/g (20 min); heart 6.98 +/- 0.38 (0 min) to 6.17 +/- 1.07 (20 min); kidney 8.23 +/- 0.86 (0 min) to 3.76 +/- 0.54 (20 min). We present data on energy derangement in a rat model of PA, closely resembling the clinical situation, showing that energy depletion precedes cell damage and death.

Cholinergic, monoaminergic and glutamatergic changes following perinatal asphyxia in the rat

Perinatal asphyxia (PA) is considered to lead to a variety of brain disorders including spasticity, epilepsy, mental retardation, and minimal brain disorder syndromes and may form the basis for psychiatric and neurodegenerative diseases later in life. We examined markers for neuronal transmission involved in the pathomechanisms of PA and candidates as mediators for long-term sequelae. We tested tyrosine hydroxylase (TH) and the vesicular monoamine transporter (VMAT) representing the monoaminergic system, the vesicular acetylcholine transporter (VAChT), and the excitatory amino acid carrier 1 (EAAC1), a neuronal subtype of the glutamate transporter, using immunohistochemistry on brain sections of rats subjected to graded PA. Three months following the asphyxiant insult immunoreactive (IR)-TH was decreased in striatum, hippocampus, thalamus, frontal cortex, and cerebellum; IR-VMAT was increased, and IR-VAChT was decreased in striatum. IR-EAAC1 glutamate transporter was increased in frontal cortex. The cholinergic, monoaminergic, and glutamatergic changes, still observed 3 months after the asphyxiant insult, may reflect their involvement in the pathomechanisms of PA and indicate mechanisms leading to long-term complications of PA. The variable consequences on the individual markers in several brain regions may be explained by specific susceptibility of cholinergic, monoaminergic, and glutamatergic neurons to the asphyxiant insult.

Effects of endotracheal suctioning in high-frequency oscillatory and conventionally ventilated low birth weight neonates on cerebral hemodynamics observed by near infrared spectroscopy (NIRS)

Adverse changes in cerebral hemodynamics during endotracheal suctioning have been reported in conventionally ventilated newborns, whereas observations on the effect of endotracheal suctioning during high‐frequency ventilation have not been reported to date. The present study was designed to investigate the effect of endotracheal suctioning on cerebral hemodynamics in high‐frequency and conventionally ventilated infants. Changes in cerebral concentration of oxygenated (cO2Hb) and deoxygenated hemoglobin (cHHb) and oxidized cytochrome aa3 (cCyt.aa3) were measured by noninvasive near‐infrared spectroscopy. In an open prospective study, 26 suctioning periods in 9 high‐frequency and in 6 conventionally ventilated newborn infants were investigated. Heart rate, arterial oxygen saturation (SaO2), mean blood pressure (MABP), and transcutaneous carbon dioxide tension (TcpCO2) were monitored continuously.

Microbial invasion of the amniotic cavity at birth is associated with adverse short-term outcome of preterm infants.

Abstract Aims: To determine the frequency and clinical significance of microbial invasion of the amniotic cavity at the time of delivery in preterm infants. Methods: Prospective cohort study during June 2001 and January 2002. Preterm infants < 33+6 weeks of gestation who had amniotic fluid and placental tissue sampled for culture during cesarean section were included. Results: Of a total of 80 neonates, 42 had negative culture results, 22 had growth of Ureaplasma urealyticum, and 16 had growth of other pathogens. Isolation of Ureaplasma urealyticum was associated with a decreased risk of developing hyaline membrane disease after birth but a more than 20 times increased risk of developing chronic lung disease. Patients with growth of other pathogens had a significantly higher mortality than patients with negative culture results. Conclusions: Isolation of microorganisms from the amniotic cavity at birth is associated with an adverse outcome of the preterm infant. In the light of extremely small numbers of positive blood cultures in preterm infants after birth, we consider it reasonable to recommend routine culturing of amniotic cavity tissues/fluid obtained during cesarean section in order to increase the identification rate of pathogens potentially involved in the pathogenesis of perinatal infections.

Pain and stress management in the Neonatal Intensive Care Unit — A national survey in Austria

ZusammenfassungNeugeborene sind — entgegen langjähriger Meinung — zur Schmerzwahrnehmung fähig und zeigen eine Vulnerabilität für schmerzreaktive Kurzzeit-und Langzeitkonsequenzen.Die Ursache eines inadäquaten analgetischen Managements ist zum einen begründet im mangelnden Bewusstsein, dass Neugeborene, besonders Frühgeborene Schmerzen empfinden können, viel mehr jedoch im Respekt vor potentiellen Nebenwirkungen von zentral wirksamen Medikamenten. Ziel der Studie ist die Erfassung gegenwärtigen Vorgehens zur Schmerzprävention, Analgesie und Sedierung in der Neonatologie.Die Arbeit umfasst die Ergebnisse einer Österreich weit durchgeführten Erhebung an neonatologischen Intensivstationen.Alle Befragten bestätigen, dass Neu- und Frühgeborene Schmerzen sowohl wahrnehmen als auch ausdrücken können, und nahezu alle meinten, Schmerz und die Reaktion darauf beeinflusse die neonatale Morbidität. Validerte Schmerzerfassungs-Scores werden an 11% aller befragten neonatologischen Intensivstationen (NICUs) angewandt, an 75% existieren standardisierte Analgesieprotokolle und an allen Abteilungen (100%) werden auch nicht pharmakologische Behandlungsstrategien angewandt. Die Anwendung präventiver Maßnahmen im Rahmen routinemäßig durchgeführter, schmerzhafter Prozeduren erfolgt in 8% bis 95%. In 8% findet Schmerzprävention vor Nabelgefäßkatheter Implantation statt, in 29% und 46% vor subcutanen Injektionen bzw. Fersenstich. Nahezu alle verabreichen Analgetika vor Lumbalpunktionen und Thoraxdrainagen und 100% im Falle einer elektiven Intubation.SchlussfolgerungDas Bewusstsein der Wertigkeit und Auswirkungen von Stress bei Neugeborenen, verursacht durch Schmerzen, ist unter Neonatologen sehr groß. Dennoch wird die Notwendigkeit einer suffizienten Analgesie bei dieser sensitiven Patientenpopulation nach wie vor unterschätzt. Kontinuierliche Fortbildung und Information über die sichere Anwendung analgetischer Medikation in der Neonatologie sind unumgänglich.SummaryNeonates are sensitive to pain and vulnerable to both its short-term and long-term effects. Management of analgesia is thought to be hampered by lack of awareness that newborns are capable of experiencing pain and by fears about adverse effects associated with analgesics. The purpose of this study was to assess current medical practice in preventive analgesia and sedation in the neonate throughout Austria.This report details the results of a survey in 28 neonatal intensive care units (NICUs) in Austria. Data collection took place from October to December 2001.All NICUs reported the capability of newborns to experience and express pain and nearly all stated the possibility of pain affecting morbidity. Validated scores for pain assessment were used by 11% of NICUs, standardized protocols for analgesia existed in 75%, and 100% practiced non-pharmacological treatment strategies. The use of preventive measures in routinely performed painful procedures ranged from 8% to 96%. For example, only 8% of NICUs prevent distress and pain prior to umbilical vessel catheterization, 29% prior to subcutaneous injections and 46% prior to heel lancing. Nearly all NICUs apply analgesia before lumbar puncture and thoracicdrain placement, and all use analgesic and/or sedative medication in elective intubation.ConclusionThere is widespread awareness among neonatologists of the importance and effects of distress caused by pain in newborns. However, the necessity of providing sufficient analgesia is underestimated. Further information on the safety of analgesic drugs in neonatology is imperative.

Microdissection and reverse painting reveals a microdeletion 6(q26qter) in a de novo r(6) chromosome

Ring chromosomes 6 are rare constitutional abnormalities with inconsistent phenotypic and clinical features. One of the reasons for this variability is the cytogenetically undetectable loss of chromosomal material from the telomeric segments at 6p or 6q. We have therefore used fluorescence in situ hybridization (FISH) to analyse a ring chromosome 6 that was detected in a newborn boy with dysmorphic features. Reverse painting of the microdissected ring chromosome onto normal metaphase spreads revealed a small deletion of the terminal region of the long arm, 6(q26qter). Moreover, the simple all-telomeric sequence (TTAGG)n was lost, whereas the p-specific subtelomeric sequence was still present. Our findings confirm that microdeletions occur during the formation of r(6) chromosomes and, therefore, are an important determinator of the associated phenotype.

Echocardiographic evidence of aortopulmonary collaterals in premature infants after closure of ductus arteriosus

Aortopulmonary collaterals occur in a variety of congenital heart diseases, in chronic pulmonary infection and abscesses, in association with lung tumors, and after multiple pulmonary emboli. In patients with congenital cyanotic heart disease aortopulmonary collaterals mainly occur in conditions with reduced pulmonary blood flow. We investigated 12 preterm low-birth-weight infants, gestational age 29.3+/-3.3 weeks, with respiratory failure who suffered from moderate to severe chronic lung disease after a period of mechanical ventilation. All patients developed aortopulmonary collaterals after closure of a patent ductus arteriosus. Aortopulmonary collaterals could be displayed clearly by color Doppler echocardiography and originated mainly from the descending aorta or the aortic arch. Hypoxic and hypercapnic episodes favored the development of aortopulmonary collaterals, which disappeared after pulmonary hemodynamics and respiratory function had improved. In only one patient coiling of a large col lateral vessel had to be performed. Systemic-to-pulmonary collateral vessels potentially aggravate chronic lung disease by increasing collateral pulmonary blood flow and reducing lung compliance. We conclude that aortopulmonary collaterals occur in bronchopulmonary dysplasia and can cause major problems in ventilated premature infants. Echocardiographic evaluation is important to prevent aggravation of chronic lung disease of infants at risk.