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Biomedical subjects

H Lagercrantz

Publications and source records attributed to H Lagercrantz.

At least 127 records · Page 7Linked to original sources
PubMed1991

[Functional development of the brain in the fetus and the infant].

Neuronal multiplication occurs mainly from the 10th to the 20th gestational weeks, after which probably no new nerve cells are formed, though neuronal arborisation and the formation and re-organisation of synapses continues until adulthood. An intriguing question is how the blueprint for the formation of about 100 billion nerve cells and their dendrites and synapses can be contained in the human genome. Environmental factors are probably crucially involved in the development of the brain, particularly from the later stages of gestation onwards. Somatosensory functions are developed at an early stage. The pain threshold is assumed to be lower in the fetus than in the adult. In man, general fetal movements appear from the 8th gestational week, and more complex movements such as sucking, swallowing and breathing during the 10th-12th gestational weeks. These movements are generated by neuronal networks, and seem to occur spontaneously without any sensory stimulation. At birth there is a general excitation of the infant, and the neonate is awake and aroused. Studies in rats have shown a multifold increase in noradrenaline turnover to occur in the brain stem at birth, which is assumed to be related to the arousal of the newborn. Recent studies have shown that there is a switch-on of various excitatory neuropeptide genes at birth, and an increase in noradrenaline in the locus coeruleus which is assumed to be the arousal centre.

Behavior↗
PubMed1991

Enhanced in vivo release of substance P in the nucleus tractus solitarii during hypoxia in the rabbit: role of peripheral input.

In the adult, pentobarbitone-anaesthetized rabbit, the in vivo release of substance P-like immunoreactivity was measured in the nucleus tractus solitarii using microdialysis and radioimmunoassay. Increased 160 +/- 16%) extracellular concentrations of substance P-like immunoreactivity were observed during hypoxic provocations of 9% O2 in N2 which also resulted in an increase in phrenic nerve activity. In bilateral carotid sinus nerve-denervated animals no enhanced release of substance P was seen in response to hypoxic challenges (105 +/- 6%) and the phrenic nerve activity was not significantly affected. Perfusion of the nucleus tractus solitarii region with the dopamine agonist, apomorphine (10(-5) M) resulted in a significant decrease in the extracellular level of substance P. These results provide further evidence that substance P is involved in the mediation of the hypoxic drive inputs from the peripheral chemoreceptors. The interactions of apomorphine with substance P release might also suggest a presynaptic modulation of substance Pergic neurons by dopamine in the nucleus tractus solitarii.

Animals↗
PubMed1991

Establishment of functional residual capacity in infants delivered vaginally and by elective cesarean section.

Functional residual capacity (FRC) was measured with an open circuit N2 washout method in 20 vaginally born infants and 15 delivered by cesarean section, 30 and 120 min after birth. Umbilical artery blood was collected and analyzed for pH and catecholamine concentration. FRC was significantly higher in the cesarean section infants than in the vaginally delivered infants at 120 min of age (23.8 versus 16.8 ml/kg). The cesarean section infants also tended to have lower tidal volumes and higher respiratory frequencies than infants delivered vaginally. No significant correlation was found between catecholamine levels in umbilical artery and FRC in either group although there was a significant correlation between catecholamine level at birth and the increase of FRC from 30 to 120 min in the cesarean section group. It is suggested that the higher FRC, higher respiratory frequency and lower tidal volume in the cesarean section infants is an adaptation to a higher pulmonary water content to ensure an efficient gas exchange with the least respiratory work.

Catecholamines↗
PubMed1991

Delayed neurological adaptation in infants delivered by elective cesarean section and the relation to catecholamine levels.

We have studied the effect of mode of delivery and catecholamine (CA) surge at birth on neurobehaviour 1, 2 and 5 days after birth. Fifteen full-term infants were delivered by elective cesarean section (CS) and 15 full-term control infants were born vaginally. Infants born after elective CS were less excitable and had significantly reduced number of optimal responses during the first 2 days after delivery, compared to the controls. On the 5th day no significant neurological differences were found between the groups. Adrenaline and noradrenaline (NA) in umbilical arterial plasma were analysed in all infants. The mean values of NA were lower in the CS infants as compared to the vaginally delivered infants. Statistically significant correlations were found between low CA levels and poor muscle tone and/or lower grade of excitability in the CS infants. These results suggest that the high CA surge at birth might be of importance for the neurological adaptation after birth.

Adaptation, Physiological↗
PubMed1991

Hypoxia-mediated in vivo release of dopamine in nucleus tractus solitarii of rabbits.

A wide variety of neuroactive substances have been suggested to be involved in the respiratory depression observed in response to severe hypoxia. By use of the technique of microdialysis, the release of dopamine (DA) was measured in the nucleus tractus solitarii during severe hypoxic provocations (6% O2 in N2) in the adult pentobarbital-anesthetized rabbit. DA release was analyzed by high-performance liquid chromatography with electrochemical detection. Such hypoxic provocations caused pronounced phase of depression in the phrenic nerve activity and enhanced release of DA. After bilateral carotid sinus nerve denervation, acute severe hypoxia did not give rise to enhanced release of DA or to phrenic nerve depression. Mild hypoxic (9% or 12% O2 in N2) or hypercapnic (6% CO2) stimuli resulted in an increased phrenic nerve activity without any concomitant changes in DA release. Decerebration at the midcollicular level in rabbits prevented an enhanced release of DA in the nucleus tractus solitarii during severe hypoxia. The results suggest that 1) DA is involved in the central ventilatory response to severe hypoxia, 2) not only the initial excitatory but also the second depressive phase in response to severe hypoxia is mediated partially by the peripheral chemoreceptors, and 3) the depressive phase is dependent on intact connections from suprapontine structures.

Animals↗
PubMed1991

CO2-sensitivity in newborn and young infants tested by the rebreathing method. Methodological aspects.

The rebreathing method in newborn and young infants was tested with regard to the effects of increasing levels of CO2 on the behavioral state and to the influence of facial stimulation caused by the use of a face mask and pneumotachograph on the breathing pattern. Successive increases in inspired CO2 levels from 3 to 8.5% did not change the behavioral state. The application or removal of a face mask, with or without an attached pneumotachograph, caused an immediate disruption in the breathing pattern which lasted 10-40 s. Thereafter, breathing stabilized. When only the face mask was used, the increases in minute ventilation, tidal volume and cycle duration of 7, 13 and 5%, respectively, were transient and lasted for 40-50 breaths. The breathing then returned to control levels. In contrast, breathing through the face mask connected to the pneumotachograph caused a long-lasting increase in ventilation (12%) due to the retention of CO2 in the spirometric circuit. We conclude that the inhalation of a continuously increasing mixture of 3-8.5% CO2 in O2 did not influence the behavioral state and that the effect of face mask on breathing pattern was transient.

Carbon Dioxide↗
PubMed1991

Birth-related activation of preprotachykinin-A mRNA in the respiratory neural structures of the rabbit.

The perinatal ontogeny of preprotachykinin-A gene expression was assessed in central respiration-related structures. On the day of birth, there was an enhanced expression of preprotachykinin-A mRNA in the region of the nucleus tractus solitarii, the primary relay station for respiratory and cardiovascular reflexes. This increased expression was also seen in the pups delivered by cesarean section and allowed to breathe for a couple of hours as compared with their littermates, which were not allowed to breathe at all. On the basis of this finding, we suggest that the commencement of continuous breathing at birth, unlike the episodic breathing of fetal life, is associated with the enhanced expression of preprotachykinin-A mRNA in the nucleus tractus solitarii.

Animals↗
PubMed1991

Changes in levels of mRNA coding for catecholamine synthesizing enzymes and neuropeptide Y in the adrenal medulla of the newborn rat.

We have measured levels of mRNA coding for the catecholamine synthesizing enzymes tyrosine hydroxylase (TH), dopamine beta-hydroxylase (D beta H), phenylethanolamine N-methyltransferase (PNMT) and for neuropeptide Y (NPY) in rat adrenal medulla by using in situ hybridization histochemistry. Ages of one day before birth (E21), 12 h, 24 h, 2 days and 4 days after birth and in adults were studied. TH, D beta H and NPY mRNA levels increased markedly postnatally. Twelve hours after birth the levels of mRNA for TH, D beta H and NPY were, respectively, 512 +/- 18%, 370 +/- 24% and 253 +/- 21% of E21 levels. At 24 h of age NPY mRNA level was 437 +/- 73% of fetal value. In contrast, the levels of mRNA coding for PNMT increased more slowly and reached 196 +/- 9% of E21 level on postnatal day four and was further increased in adult rats.

Adrenal Medulla↗
PubMed1991

[Functional development of the brain in the fetus and the newborn infant].

Neuronal multiplication occurs mainly from the 10th to the 20th gestational weeks, after which probably no new nerve cells are formed, though neuronal arborization and the formation and re-organisation of synapses continues until adulthood. An intriguing question is how the blueprint for the formation of about 100 billion nerve cells and their dendrites and synapses can be contained in the human genome. Environmental factors are probably crucially involved in the development of the brain, particularly from the later stages of gestation onwards. Somatosensory functions are developed at an early stage. The pain threshold is assumed to be lower in the fetus than in the adult. In man, general fetal movements appear from the 8th gestational week, and more complex movements such as sucking, swallowing and breathing during the 10th-12th gestational weeks. These movements are generated by neuronal networks, and seem to occur spontaneously without any sensory stimulation. At birth there is a general excitation of the infant, and the neonate is awake and aroused. Studies in rats have shown a multifold increase in noradrenaline turnover to occur in the brain stem at birth, which is assumed to be related to the arousal of the newborn. Recent studies have shown that there is a switch-on of an excitatory neuropeptide genes at birth, and an increase in noradrenaline in the locus coeruleus which is assumed to be the arousal centre.

Brain↗
PubMed1990

Human fetal sympathoadrenal responsiveness.

A reference range of fetal noradrenaline levels related to gestational age was calculated from 27 normal pregnancies between 16 and 36 weeks of gestation. Growth retarded, hypoxic fetuses had significantly elevated noradrenaline levels (P less than 0.01).

Adrenal Glands↗
PubMed1990

Development of the arterial chemoreflex and turnover of carotid body catecholamines in the newborn rat.

1. The peripheral, arterial chemoreceptors in the carotid body are active and responsive in the fetus. At birth, when oxygenation increases, the chemoreceptors are silenced. Over the next few days the sensitivity is reset toward the adult level and the chemoreceptors influence breathing during normal conditions. In order to investigate the underlying mechanisms of this resetting we examined the strength of the chemoreflex in newborn rats and correlated this to the contents of dopamine and noradrenaline in the carotid bodies of the newborn pups and near-term fetuses. Furthermore, turnover rates of dopamine and noradrenaline were determined in newborn rats up to 1 week of age by analysis of catecholamine decreases after inhibition of synthesis with alpha-methyl-p-tyrosine. 2. Chemoreceptor influence was assessed by the method of 'physiological chemodenervation' with hyperoxia of 15-20 s duration in unanaesthetized rat pups. Relative changes in ventilation elicited by hyperoxia were determined by body plethysmography. We found no change in ventilation on the day of birth either in vaginally born rats or in near-term pups delivered by Caesarean section. After 1 day there was a significant decrease in ventilation of -19.4 +/- 2.3% (mean +/- S.E.M.) and at 7 days of age the decrease was -28.8 +/- 2.2%, suggesting an increasing influence from the peripheral chemoreceptors. 3. The contents of dopamine and noradrenaline were measured by high-performance liquid chromatography. Dopamine increased from 3.7 +/- 0.4 pmol (pair of carotid bodies)-1 in the fetus to a peak of 15.9 +/- 2.6, 6-12 h after birth followed by a decline to 7.1 +/- 0.7 at 7 days of age. Noradrenaline levels increased from 1.3 +/- 0.3 in the fetus to 9.6 +/- 1.1 pmol (pair of carotid bodies)-1 after 4 days. The turnover rate of dopamine decreased from 4.4 pmol (pair of carotid bodies)-1 h-1 0-6 h after birth to 1.0 at 6-12 h of age. The turnover rate of noradrenaline also decreased over the first hours following delivery. 4. Since dopamine is an inhibitory neuromodulator in this system, we suggest that the increase in sensitivity seen after the first day of life is, at least in part, due to a decrease in the release of dopamine and thus a removal of an inhibitory mechanism.

Animals↗
PubMed1990

Plasma gastrin and somatostatin in newborn infants and their relationship to catecholamines.

We investigated the relationship between gastrin and somatostatin, and catecholamine concentrations in the cord blood of newborn infants. We also measured the levels of the two peptides during the first postnatal hours in the infants and furthermore characterized their molecular pattern. Twenty-two healthy infants who had been born at term were studied. Blood samples were collected from the umbilical cord and from the infants 0.5 h and 3.5 h after delivery. Peptides were measured with radioimmunoassay and further characterized by HPLC. Catecholamines were analysed by HPLC. We found that gastrin and somatostatin concentration in the umbilical cord blood was 106 +/- 40 pmol/l and 29 +/- 17 pmol/l, respectively. A significant relationship between the concentrations of somatostatin and noradrenaline in cord blood was found, (r = 0.7, n = 11, P less than 0.01). No such relation was found for gastrin. No change occurred in gastrin concentrations postnatally. Somatostatin concentration in the blood collected from the infant 0.5 h and 3.5 h after delivery was 19 +/- 11 pmol/l and 16 +/- 7 pmol/l, respectively. These concentrations were significantly lower (P less than 0.01) compared to the level measured in cord blood. Circulating gastrin was found to correspond to non-sulphated gastrin-34 and somatostatin to both somatostatin-28 and somatostatin-14. The proportion of somatostatin-28 was 30-40% and of somatostatin-14, 60-70%. We conclude that the somatostatin level, but not the gastrin level is influenced by the degree of fetal stress during labour, as evidenced by the relationship with noradrenaline. The gastrin level remained unchanged during the 3.5 h following delivery, whereas the somatostatin level decreased significantly during the same time.

Adult↗
PubMed1989

Respiratory and arousal responses to hypoxia in apnoeic infants reinvestigated.

Respiratory and arousal responses to mild hypoxia (15% oxygen in nitrogen) were recorded in 18 healthy infants and 33 infants who had sustained severe sleep related apnoeic events (ALTE). Respiratory movements and transcutaneous gas pressures (tcPO2 and tcPCO2) were continuously monitored during the 10 min test. The changes in tcPCO2 in relation to the decrease in tcPO2 were used as an index of the ventilatory and metabolic responses to hypoxia. We found that the response of apnoeic infants was within the range of the controls although the distribution of the individual response slopes was shifted towards the lower end of the range. Arousal was observed in 33% of apnoeic infants and 32% of the controls. Regular periodic breathing occurred in 42% of apnoeic infants compared to 28% of controls. In contrast to the controls, periodic breathing in apnoeic infants was not associated with a drop in tcPCO2 to below baseline levels. Apnoeic infants also alternated between regular and periodic breathing during the test. These findings are suggestive of a weak feed back control of breathing but do not support former views of a deficient hypoxic response in infants with ALTE.

Arousal↗
PubMed1989

Electrocardiographic waveform changes and catecholamine responses during acute hypoxia in the immature and mature fetal lamb.

The aim of the present study was to investigate the changes in electrocardiographic waveform and the release of catecholamines in the fetal lamb during nonacidemic fetal hypoxia. Chronically instrumented fetal lambs were subjected to reproducible hypoxia by reduction of the maternal placental blood flow. This was achieved by complete obstruction of the maternal aorta for 60 seconds. The fetuses were divided into an immature (119 to 126 days, n = 10) and a mature group (129 to 141 days, n = 6). Both groups of fetuses had a marked fall in oxygen tension (from 2.43 +/- 0.12 to 1.46 +/- 0.12 and 2.22 +/- 0.15 to 1.11 +/- 0.17 kilopascals [kPa] in the immature and mature groups, respectively) and in oxygen saturation (from 48% +/- 3% to 17% +/- 2% and 49% +/- 3% to 15% +/- 3%, respectively), but only modest changes occurred in pH and carbon dioxide tension. Basal fetal catecholamine concentrations did not differ between the groups but increased more significantly in the mature group with acute hypoxia. An increase in the T wave amplitude of the fetal electrocardiogram occurred in both groups during the latter part of occlusion with peak values shortly after removal of the occlusion. A linear correlation was found between the plasma epinephrine concentration and the T/QRS ratio in the mature group. Fetuses in both groups showed a marked bradycardia of similar magnitude during the occlusion but differed during the early phase of heart rate recovery by a slower acceleration of heart rate in the mature group. In connection with this marked bradycardia, the mature group showed a significant rise in mean arterial blood pressure at end of the occlusion. We suggest that fetal maturity has a significant influence no only on the release of catecholamines during nonacidemic hypoxia but also on the cardiovascular reaction pattern and changes in the ST waveform.

Acute Disease↗
PubMed1989

Hypoxia reinforces laryngeal reflex bradycardia in infants.

The laryngeal chemoreflex involves bradycardia, apnea, swallowing and peripheral vasoconstriction. This reflex was studied in twelve infants, aged 5 days-28 weeks, who had sustained an apparent life-threatening event or were siblings of infants who had died of the sudden infant death syndrome. The bradycardic and apneic components of the reflex were found to be significantly, and sometimes powerfully, reinforced when elicited by pharyngeal water instillation during acute, mild hypoxia (transcutaneous PO2 4.6-8.3 kPa). Apnea duration during normoxia was 0.7-15 sec, and during hypoxia 2-30 sec. Heart rate change ranged from +26% to -21% during normoxia, as compared with -4% to -63% during hypoxia. The percentage change in heart rate was found to inversely correlate with the transcutaneous PO2-level prevailing when the reflex was elicited. The conclusion is that there is a significant reinforcement of the cardiorespiratory adjustments when the laryngeal reflex is activated during simultaneous excitation of the peripheral arterial chemoreceptors. One infant, showing a particularly strong increase of the cardiorespiratory response to laryngeal receptor stimulation during hypoxia, later died of sudden infant death syndrome.

Blood Gas Monitoring, Transcutaneous↗