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Biomedical subjects

H Lagercrantz

Publications and source records attributed to H Lagercrantz.

At least 73 records · Page 4Linked to original sources
PubMed1997

Heart rate response profiles during head upright tilt test in infants with apparent life threatening events.

Sympatheticovagal imbalance causing episodes of severe bradycardia has been suggested as a cause of apparent life threatening events (ALTEs). The autonomic control of the heart rate in 18 infants with ALTEs and 12 controls was evaluated by the head upright tilt test. Five different heart rate response profiles (compared with the baseline) were observed during the tilt: (1) increase followed by a decrease and return to baseline; (2) sustained increase; (3) decrease followed by an increase and return to baseline; (4) sustained decrease; (5) no change. Eighty eight per cent of controls responded with heart rate increase followed by decrease or sustained increase compared with 55% of infants with an ALTE; a significantly greater proportion of infants with ALTEs than controls responded with heart rate decrease or no change in rate (45% v 8%). This altered reaction during a head upright tilt test may be an expression of an underlying autonomic dysfunction in infants who have experienced an ALTE.

Case-Control Studies↗
PubMed1997

Different expression and mobilisation of the complement regulatory proteins CD35, CD55 and CD59 in neonatal and adult neutrophils.

We investigated the expression and the N-formyl-methionyl-phenylalanine (fMLP)- and interleukin-8 (IL-8)-induced mobilisation of the complement regulatory proteins CR1 (CD35), decay-accelerating factor (CD55) and CD59 on neutrophils in neonates and adults. The expression of CD35 on resting neonatal neutrophils was significantly higher than in adults. Both fMLP and IL-8 increased CD35 expression more markedly in adults. CD55 on resting neutrophils in neonates was significantly higher than in adults, but did not further increase upon fMLP stimulation as opposed to adults. The increase in CD59 expression was more pronounced in adult neutrophils and was significantly higher than in neonates after fMLP activation. The addition of the protease inhibitor phenylmethanesulphonyl fluoride during fMLP activation improved the upregulation of CD35 significantly more in neonates, but not CD55 or CD59. This effect could be replaced by human normal sera. These data demonstrate that differences exist between neonatal and adult neutrophils with respect to the expression and mobilisation of functional receptors related to protection from autologous complement lysis and may indicate differences in the efficiency to circumvent complement-mediated cell damage at the inflammatory site.

Adult↗
PubMed1997

Effects of hyperglycemia on gasping and autoresuscitation in newborn rats.

The aim of this study was to test the effects of glucose on the gasping ability and survival in a rat pup model during acute anoxia. Newborn rat pups of both 1 and 8 days of age were given glucose (30 and 60 mg/animal) or saline intraperitoneally and subsequently subjected to anoxia (100% N2). Glucose supplement induced hyperglycemia. Respiration was recorded by barometric plethysmography. The rat pups responded to acute anoxia with a robust sequence of respiratory pattern: hyperpnea, primary apnea, hypoxic gasping and secondary apnea. During anoxia the 1-day-old rats gasped much longer than the 8-day-old rats (23.4 +/- 1.0 vs. 6.1 +/- 0.5 min, p < 0.001). No difference was found in gasping duration between the saline control and the glucose-supplemented 1-day-old rat pups. The 8-day-old supplemented rats gasped much longer (9.3 +/- 0.5 min) than the control rats (6.1 +/- 0.5 min, p < 0.01). The animals autoresuscitated when they received oxygen (100%) during the gasping period. When oxygen was given after the gasping period, the survival rate was 33.3% in control and 0% in supplemented 1-day-old rats, and 100% in control and 50% in glucose-supplemented 8-day-old rats (p < 0.02). Further controlled experiments for a fixed period of anoxia to 13.5 min resulted in survival rates of 50.0% for controls and 28.6% for supplemented animals, respectively. The overall survival rate was then 85.2% in control and 52.9% in supplemented 8-day-old rats (p < 0.05). Lactate concentration in blood rapidly increased in the first 6 min of anoxia and thereafter gradually increased to 22.1 mmol/l around the last gasp in the 1-day-old rats. Hyperglycemia did not cause further accumulation of lactate despite a transient elevation over the control rats at 6 min of anoxia. In the 8-day-old supplemented animals the lactate level was only modestly increased, probably due to the prolonged gasping period. In conclusion, we found that gasping performance was well preserved in the 8-day-old glucose-supplemented rats, whereas the autoresuscitation mechanism after the last gasp might be altered due to hyperglycemia. In addition, the accumulation of lactate in the blood did not affect the gasping performance and the mechanisms of autoresuscitation.

Animals↗
PubMed1997

Long-term impairment in the neurochemical activity of the sympathoadrenal system after neonatal hypoxia in the rat.

The study evaluates the long-term effect of neonatal hypoxia on the neurochemical activity of the sympathoadrenal system in the rat. One-day-old male pups were exposed to hypoxia (10% O2) for 6 d and thereafter reared under normoxia. Neonatal hypoxia reduced the body weight of 3- and 8-wk-old rats and did not change the blood pressure at 6 wk of age. In sympathetic ganglia, the content and/or turnover rates of norepinephrine were reduced in neonatal-hypoxic rats of 3 and 8 wk of age, but the content and turnover rates of dopamine were unaltered. The effect was not dependent on the type of ganglion. In the superior cervical ganglion, neonatal hypoxia had a selective effect on the type of catecholamine (dopamine versus norepinephrine), thus suggesting a selective-altered maturation of noradrenergic neurons, but presumably not of the dopaminergic small, intensely fluorescent cells. A long-term deficiency in adrenal activity was the consequence of neonatal hypoxia, as shown by the decrease in the content and turnover rate of dopamine. Neonatal hypoxia elicited a long-term decrease in the content and turnover rates of norepinephrine in heart and lungs but failed to induce a significant effect in kidneys. However, this effect was not tissue-specific. Data provide evidence that a hypoxic episode occurring during a critical period of development in the rat induces a long lasting decrease in the neurochemical activity of the sympathoadrenal system. These results are discussed in terms of their implications for human pathology.

Adrenal Glands↗
PubMed1997

Adenosine modulates inspiratory neurons and the respiratory pattern in the brainstem of neonatal rats.

The role of adenosine in the modulation of respiration-related neurons was examined using an in vitro brainstem-spinal cord preparation from neonatal rats (0-4 d old). Respiratory activity was recorded from the C4 or C5 ventral roots by suction electrodes and from inspiratory related neurons (I neurons) in the rostral ventrolateral medulla by microelectrodes. The following substances were added to the preparation superfusate, and their effect was evaluated: the adenosine A1 receptor agonist N6-(2-phenylisopropyl)adenosine, R(-)isomer (R-PIA), the adenosine uptake blocker dipyridamole, the adenosine receptor antagonist theophylline, and the specific A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). R-PIA and dipyridamole decreased the activity of I neurons and the C4 respiratory burst rate. Furthermore, these compounds induced a significantly more irregular respiratory rate in three-quarters of preparations from the youngest animals (<48 h old) compared with that of controls. Theophylline or DPCPX reversed the effects of both R-PIA and dipyridamole on respiratory rate, regularity of respiratory rate, inspiratory time, amplitude, and intra-burst frequency of I neurons. Thus, adenosine depresses both the I neurons in the rostral ventrolateral medulla and the respiratory motor output. This depression of I neurons and respiratory rate can be abolished by theophylline primarily through a blockade of medullary adenosine A1 receptors. An age-dependent correlation of the effects of R-PIA and dipyridamole, with a more pronounced decrease in respiratory activity in preparations from younger animals, indicates that adenosinergic modulation of medullary respiration-related neurons changes during the first days of postnatal life.

Adenosine↗
PubMed1996

Effects of immunological sympathectomy on postnatal peptide expression in the rat adrenal medulla.

Administration of monoclonal antibodies against acetylcholinesterase (AChE-mabs) to adult rats leads to a selective degeneration of the acetylcholine esterase-(AChE), choline acetyltransferase-(ChAT) and enkephalin-(ENK) positive preganglionic fibres of the splanchnic nerve innervating the adrenal gland. Here we used this approach of immunological sympathectomy, performed at postnatal day 2 (P2), in an attempt to study the development role of the preganglionic fibres in the adrenal medulla in more detail. Analysis was performed at P16 and revealed that the effect of this treatment varied considerably between animals, as judged by the number of remaining AChE-, ChAT- and ENK-positive fibres. The number and intensity especially of ENK fibres in the adrenal medulla correlated negatively with the number and staining intensity of ENK-immunoreactive chromaffin cells, suggesting a 'dose-response' relationship. Thus, the high early postnatal levels of ENK-like immunoreactivity generally persisted in chromaffin cells of adrenals with a successful immunosympathectomy, i.e. in those adrenals that lacked AChE-, ChAT- and ENK-positive nerves. In contrast, calcitonin gene-related peptide-like immunoreactivity in nerves and chromaffin cells was not affected. Large and strongly AChE-positive intra-adrenal ganglion neurones, recently termed type I ganglion neurones, were present also after AChE-mab treatment and had an apparently normal morphology. These results indicate a role for preganglionic fibres in the developmental regulation of ENK in the chromaffin cells. However, these fibres appear less important for the postnatal development of the type I ganglion neurones.

Acetylcholinesterase↗
PubMed1996

Regional variations in skin perfusion and skin thickness may contribute to varying efficacy of topical, local anaesthetics in neonates.

The national Swedish screening programme for inborn errors of metabolism includes blood sampling from all neonates. Heel lancing has hitherto been the method of choice for these screening tests. Studies have recently been done to find out whether the use of EMLA can alleviate pain caused by heel lancing. EMLA had little, if any effect when applied to the heel of full term babies. Similar results were reported concerning preterm infants. Other authors have found that differences in skin thickness or in skin blood perfusion may influence the effect of EMLA. The aim of this study was to establish whether differences in skin thickness or in skin blood perfusion were present in three regions: the forehead, the dorsum of the hand and the heel. Ten healthy full term neonates were included in the study on skin perfusion. Measurements were made with a laser Doppler flux meter. Twenty-seven healthy full term neonates were included for measurements of skin thickness using a high frequency B-mode ultrasonic meter. The heel skin perfusion was two to three times higher than the skin perfusion at the dorsum of the hand and at the forehead but there was no significant difference when comparing skin thickness of the heel with the dorsum of the hand and the forehead. A rapid clearance of a topically applied local anaesthetic, due to high cutaneous blood flow, may explain why EMLA seems to be of little value when it is applied to the neonatal heel.

Anesthesia, Local↗
PubMed1996

Concentrations of magnesium and ionized calcium in umbilical cord blood in distressed term newborn infants with hypoxic-ischemic encephalopathy.

Magnesium and ionized calcium in mixed umbilical cord blood was assessed colorimetrically in 38 distressed and 21 healthy term newborn infants. Distressed infants with a severe or moderate degree of hypoxic-ischemic encephalopathy (HIE) (n = 8) had significantly lower (p < 0.001) concentrations of magnesium (0.52 +/- 0.08 mmol/L) compared to the control group (0.69 +/- 0.06 mmol/L). No differences in concentrations of ionized calcium between distressed and control infants were detected.

Brain Ischemia↗
PubMed1996

Transient hypertriglyceridemia of infancy.

A premature boy who had suffered from IRDS, bronchopulmonary dysplasia and retinopathy of prematurity developed massive hypertriglyceridemia (48.1 mmol/L) together with moderate hypercholesterolemia (12.6 mmol/L) at 5 months of age. Lipoprotein electrophoresis revealed a marked elevation of the level of the very low density lipoprotein fraction. There was a moderate decrease in the activity of a lipolytic enzyme, lipoprotein lipase (LPL). The child had neither liver or renal disorder nor any inflammatory disease. The hyperlipidemia disappeared spontaneously at the age of 3 years. The cause of the decreased LPL activity could not be established. A partial genetic deficiency in lipoprotein lipase appears the most likely explanation, since no signs of secondary lowering of LPL activity could be found.

Child, Preschool↗
PubMed1996

Glial fibrillary acidic protein is increased in the cerebrospinal fluid of preterm infants with abnormal neurological findings.

Glial fibrillary acidic protein (GFAP) is the structural protein of the intermediate filament of astroglia. The aims of the present study were to examine GFAP in the cerebrospinal fluid (CSF) of preterm infants at different postmenstrual ages and to evaluate the potential of GFAP to predict abnormal neurodevelopmental outcome. GFAP increased in correlation with postmenstrual age in preterm infants (n = 17) and full-term infants (n = 9). The levels were five times higher in preterm infants (n = 10) with an abnormal neonatal course and/or an abnormal neurological outcome than in healthy preterm infants. The positive predictive value of a GFAP higher than the 98th percentile of normal infants was 69%, while a GFAP level below this limit invariable predicted a good outcome. Simultaneously analysed noradrenaline, hypoxanthine and glutamate did not differ between the groups. We conclude that CSF GFAP increases with maturity and that CSF GFAP appears to be a promising marker for perinatal brain damage.

Biomarkers↗
PubMed1996

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.

Apgar Score↗
PubMed1995

Functional and developmental studies of the peripheral arterial chemoreceptors in rat: effects of nicotine and possible relation to sudden infant death syndrome.

The drive on respiration mediated by the peripheral arterial chemoreceptors was assessed by the hyperoxic test in 3-day-old rat pups. They accounted for 22.5 +/- 8.8% during control conditions, but only for 6.9 +/- 10.0% after nicotine exposure, an effect counteracted by blockade of peripheral dopamine type 2 receptors (DA2Rs). Furthermore, nicotine reduced dopamine (DA) content and increased the expression of tyrosine hydroxylase (TH) in the carotid bodies, further suggesting that DA mediates the acute effect of nicotine on arterial chemoreceptor function. During postnatal development TH and DA2R mRNA levels in the carotid bodies decreased. Thus, nicotine from smoking may also interfere with the postnatal resetting of the oxygen sensitivity of the peripheral arterial chemoreceptors by increasing carotid body TH mRNA, as well as DA release in this period. Collectively these effects of nicotine on the peripheral arterial chemoreceptors may increase the vulnerability to hypoxic episodes and attenuate the protective chemoreflex response. These mechanisms may underlie the well-known relation between maternal smoking and sudden infant death syndrome.

Animals↗
PubMed1995

Blunted peripheral chemoreceptor response to hyperoxia in a group of infants with bronchopulmonary dysplasia.

Infants with BPD often suffer from chronic hypoxia and require supplemental oxygen (O2). This might affect the sensitivity of peripheral chemoreceptors. Therefore, we assessed peripheral chemoreceptor function in 25 infants with bronchopulmonary dysplasia (BPD) of varying severity, using the hyperoxic test. These infants were compared with 35 preterm infants who did not develop BPD. All infants were tested during the 40th week of postconceptional age and their mean postnatal age was 81.5 +/- 16.3 days. Sixty percent (15/25) of the BPD infants lacked a hyperoxic response, while the proportion of nonresponders to O2 among the other groups was 20% (7/35). The intensity of this response was negatively correlated to time spent on a ventilator and positively to time without supplemental oxygen. The intensity of chemoreceptor function was closely related to the severity of BPD; none of the infants with the most severe form of BPD (grade 3) showed a ventilatory response to hyperoxia. Furthermore, infants with BPD needed significantly longer time to increase their saturation than did non-BPD infants (4.7 and 9.3 sec, respectively). We conclude that many infants with BPD, particularly those with the most severe form of the disease, have abnormally functioning peripheral chemoreceptors.

Bronchopulmonary Dysplasia↗
PubMed1995

Improved understanding of respiratory control--implications for the treatment of apnoea.

Recurrent apnoea of prematurity should probably be regarded as more or less a physiological phenomenon providing that it is not precipitated by for example septicaemia and cerebral haemorrhage since the fetus of the corresponding age is only breathing episodically. Neonatal apnoea is probably not caused by a deficient respiratory rhythmic regeneration, but rather by respiratory inhibitory mechanisms induced by hyperthermia, hypoxia and adenosine. A more physiological approach should be taken in the treatment of apnoea. Some warning against the extensive use of xanthine derivatives should be raised.

Apnea↗