Ingrid Dahlin

Adenosine concentration in umbilical cord blood of newborn infants after vaginal delivery and cesarean section

ABSTRACT: Umbilical blood was collected immediately at birth (<30 s) in full-term infants after vaginal deliveries (n = 33) and elective cesarean sections (n = 11). Blood gases, plasma adenosine, hypoxanthine, and catecholamine concentrations were determined. In vaginally born infants the median arterial adenosine concentration was found to be 0.46 μM (range 0.13-2.06) and the venous 0.48 μM (0.09-1.62). These levels were significantly higher (p < 0.01) than in infants delivered by elective cesarean section; 0.16 μM (0.04-0.42) in the artery and 0.17 μM (0.02-0.56) in the vein. Vaginally born infants showed about a 4-fold higher level of umbilical arterial catecholamines than infants born by elective cesarean section. There was a strong inverse correlation between arterial hypoxanthine concentration and pH (r =-0.81, p < 0.01). It is suggested that increased adenosine release at vaginal delivery modulates the stress response elicited by the strong catecholamine surge and may furthermore exert protective effects in perinatal asphyxia.

Ethanol alters the effect of kappa receptor ligands on dopamine release in the nucleus accumbens.

Repeated exposure to ethanol has previously been shown to induce alterations in both midbrain dopamine and dynorphin systems. The aim of this study was to investigate functional changes in the sensitivity of dynorphin/kappa-receptor systems following repeated ethanol administration, using dopamine as an indirect marker. The effects of kappa-opioid receptor ligands on dopamine release in the rat nucleus accumbens were investigated following repeated ethanol administration (2 g/kg body weight, twice daily for 7 days). The selective kappa-receptor agonist U50, 488H reduced dopamine levels in both ethanol- and saline-treated animals, although the decline had a later onset and lasted shorter in the ethanol-treated group. Nor-binaltorphimine, a kappa-antagonist, produced a significant increase of dopamine in ethanol-treated rats, but lacked effect in the saline-treated group. This change in responsiveness of dopamine neurons following repeated ethanol administration could be related to changes in the sensitivity of kappa-receptor systems and/or an increase in dynorphin tone in the nucleus accumbens.

Monoamine Neurotransmitters and Metabolites in the Cerebrospinal Fluid following Perinatal Asphyxia

While the release of neurotransmitters is involved in the pathophysiology of brain damage following birth asphyxia, it also plays a role in endogenous defense against such damage. Levels of monoamines and the main cerebral monoamine metabolites in the cerebrospinal fluid (CSF) were measured in asphyxiated and control infants within 24 h after birth. The results indicate an increased turnover of noradrenaline (NA) and dopamine following asphyxia. Furthermore, the NA stores in the brain seem to be exhausted in some cases. We conclude that this increase in catecholamine turnover to some extent explains the clinical symptoms of hypoxic-ischemic encephalopathy and that it may reflect an intrinsic adaptive capacity to perinatal distress.

Cerebrospinal Fluid of Newborn Infants Contains a Deglycosylated Form of the Intermediate Filament Nestin

Nestin is an intermediate filament protein found in CNS progenitor cells. Nestin reappears in CNS tumor cells and reactive astrocytes after CNS injury. In this study we investigated whether nestin could be detected in the cerebrospinal fluid (CSF) of newborn infants and whether expression levels change with gestational age (GA) and/or brain injury. Using Western blot analysis, we examined the expression of nestin in the CSF of newborn infants(GA 25-42 wk) with asphyxia (n = 14), periventricular leukomalacia and peri(intra)ventricular hemorrhage (n = 7), and in a control group (n = 11). Protein extract from the periventricular brain tissue of a 1-wk-old infant was also analyzed. Nestin was detected in all the CSF samples and in the protein extract from the periventricular brain tissue. Although the CSF levels of nestin expression did not change with increasing GA, the asphyxia group had significantly lower levels of nestin in the CSF. An unexpected finding was that brain-derived nestin had an apparent molecular mass of approximately 240 kD, whereas all analyzed CSF samples contained two nestin-immunoreactive proteins at 200 and 220 kD. Experimental deglycosylation of the 240-kD form reduced the molecular mass to 220 kD, indicating that nestin undergoes a specific deglycosylation upon release into the CSF.

Fetal catecholamines and the Apgar score

The association between Apgar score, pH and catecholamine levels was investigated in 181 newborn infants with a gestational age between 29 and 43 completed weeks. Umbilical arterial blood was obtained before the first breath with the double clamp technique and pH was measured. Plasma adrenaline and noradrenaline were analyzed by high performance liquid chromatography. The Apgar score at 1 minute was above or equal to seven in 167 infants. Forty-four per cent of these infants had pH below 7.25. A negative correlation between log noradrenaline and pH (r = 0.52, p less than 0.001) and between log adrenaline and pH (r = 0.40, p less than 0.001) was found. In 14 infants the Apgar score was below seven. The median pH was 7.21 (range 7.02-7.32). Also in this group a negative correlation between log noradrenaline and pH (r = 0.60, p less than 0.05) and between log adrenaline and pH (r = 0.77, p less than 0.01) was noted. We concluded that the Apgar score is an insufficient measure of fetal asphyxia defined as fetal acidosis but rather reflects the vitality of the newborn.

BREATHING RESPONSE TO HYPOXIA IN RELATION TO MEASURED PLASMA NEUROMODULATORS DURING POSTNATAL DEVELOPMENT

Breathing response to 12 and 6% O2 in N2 (in isocapnia) was measured in 1-5 and 19-25 day old acute, anesthetized piglets before and after 3 mg/kg i.v. naltrexone. The degree of interaction between the anesthetic and naltrexone was assessed. At the end of each hypoxic trial, arterial blood was sampled, for measurements of pH and gas tensions, (Met)enkephalin-Arg6-Phe7, adenosine, noradrenaline and adrenaline. Results show that, as compared to older animals, young piglets (1) have greater degree of ventilatory depression in response to increasing severity of hypoxia; (2) have greater ventilatory responses with naltrexone than without the drug, and (3) demonstrate amelioration or reversal of the biphasic hypoxic response with naltrexone. Furthermore, enkephalin, adenosine, noradrenaline and adrenaline tend to increase during hypoxia in the younger animals. We conclude that, while the central role of catecholamines in respiration is uncertain at present, this study provides further evidence for the possible role of opioid peptides and adenosine in early postnatal hypoxic depression. (Supported in part by the Swedish Medical Research Council and by NIH grant HL36939 (IRM)).