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Biomedical subjects

H Lagercrantz

Publications and source records attributed to H Lagercrantz.

At least 145 records · Page 8Linked to original sources

Beta-adrenoceptor agonists and hypoxia in sheep fetuses.

Sheep fetuses, near term, were studied to test the influence of a tocolytic beta agonist, terbutaline, on fetal responses to hypoxia. After fetal exteriorization the drug was administered intravenously to the mother in three different doses: The max group comprised 11 ewes receiving 67-134 micrograms min-1. Seven ewes were given 30 micrograms min-1 and eight ewes were infused with 10 micrograms min-1. Seventeen fetuses served as controls. Hypoxia was induced by intermittent complete occlusions of the maternal abdominal aorta. Maternal terbutaline levels were high (range 50-748 nmol l-1) in the max group and the 30-micrograms group, whereas those in the 10-micrograms group were in the clinical range (range 11-58 nmol l-1). Fetuses in the max and 30-micrograms groups reacted to moderate hypoxia with excessive responses of heart rate, blood pressure myocardial contractility and ST waveform changes and a 50% mortality rate during severe hypoxia as compared with 12% in the control animals. Ten micrograms min-1 did not decrease the survival but caused an increase in myocardial workload and a negative energy balance during severe hypoxia.

Animals↗

Role of adenosine in hypoxic ventilatory depression.

The role of adenosine in the ventilatory depression induced by hypoxia was studied in 82 spontaneously breathing urethan-anesthetized 4-day-old rabbit pups. Respiration was monitored with a pneumotachograph. The animals were exposed to hypoxia (6% O2 in N2) for 30 min or until the occurrence of terminal apnea. In all animals hypoxia produced an initial increase in ventilation followed by a decrease. In the control group 52% of the animals became apneic after 7 min of hypoxic exposure. By contrast, pretreatment with dipyridamole (10 or 20 mg/kg), an adenosine uptake blocker, significantly shortened the time needed to reach apnea. Thus at 7 min of hypoxia 93% of the animals that received dipyridamole became apneic. On the other hand, administration of adenosine antagonists 8-p-sulfophenyltheophylline (5 or 8 mg/kg) and aminophylline (10 or 25 mg/kg) significantly prolonged the time required to produce apnea. Only 20% of the animals that received these antagonists became apneic at 7 min of hypoxia. These results suggest that adenosine is potentially involved in the ventilatory depression produced by hypoxia in neonatal rabbit pups.

Adenosine↗

A possible dopaminergic pathway mediating hypoxic depression in neonatal rabbits.

Previous studies show a differential effect of dopamine and its agonist apomorphine on ventilation, being depressant on adults and stimulatory on fetal respiratory breathing movements. In view of this we studied the effect of apomorphine, specific antagonists of dopamine receptors SCH 23390 (D1), sulpiride and domperidone (D2), and cis(z)-flupentixol (D1 + D2) on the typical ventilatory response to hypoxia in neonatal rabbit pups. This ventilatory response to hypoxia is characterized by an initial stimulatory (phase 1) followed by a declining (phase 2) pattern. Cis(z)-flupentixol markedly increased phase 1 and abolished phase 2. A similar effect was seen with SCH 23390. Administration of sulpiride or domperidone increased phase 1 but did not affect phase 2, thereby not altering the biphasic pattern of ventilation to hypoxia. The abolition of the biphasic response in neonatal pups on decerebration was also found to be restored by topical application of apomorphine in the fourth ventricle. Our results suggest that dopamine is acting centrally in mediating the declining phase of the biphasic response to hypoxia in rabbit pups possibly via the D1-receptors.

Animals↗

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

Umbilical blood was collected immediately at birth (less than 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 microM (range 0.13-2.06) and the venous 0.48 microM (0.09-1.62). These levels were significantly higher (p less than 0.01) than in infants delivered by elective cesarean section; 0.16 microM (0.04-0.42) in the artery and 0.17 microM (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 less than 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.

Adenosine↗

Ventilatory effects of naloxone via the sympathoadrenal system in the neonate?

Rabbit pups responded to hypoxia (6% O2 in N2) with a biphasic respiratory pattern, an initial increase by 1 min followed by a decrease. Naloxone (0.8 mg/kg) was found to abolish the declining phase of hypoxia, showing a sustained increase of ventilation throughout the hypoxic challenge. Phentolamine (30 micrograms/kg), an alpha-blocker, had no effect on the normal hypoxic response. However, pretreating the pups with phentolamine and then administering naloxone resulted in a biphasic response to hypoxia. We propose that the naloxone effects on ventilation are mediated in conjunction with the adrenergic system.

Adrenal Glands↗

Postnatal development of catecholamines and response to hypoxia in adrenals and paraganglia of rabbits.

The postnatal development of catecholamine levels in adrenals and paraganglia in newborn rabbits has been analyzed. At birth, the dominant catecholamine was noradrenaline, contributing 66% of the total catecholamine pool at day 1, 55% of which came from the paraganglia. There was a rapid postnatal increase of adrenaline, which constituted 67% of the total catecholamines at day 6 and 97% in the adult. After hypoxia at day 1, the noradrenaline levels decreased in paraganglia but not in adrenals, while adrenaline levels did not significantly change in either organ.

Adrenal Glands↗

Fetal and maternal plasma levels of gastrin, somatostatin and oxytocin after vaginal delivery and elective cesarean section.

We measured the cord levels of gastrin, somatostatin and oxytocin with radioimmunoassay in plasma collected from the umbilical artery after vaginal delivery and after elective cesarean section. Maternal venous samples after the two labour modalities were also assayed for the same hormones. Fetal gastrin, somatostatin and oxytocin levels were significantly higher after vaginal delivery than after elective cesarean section. Independently of labour type, the fetal gastrin and somatostatin levels were always higher than the maternal levels. We suggest that the observed high levels of gastrin, somatostatin and oxytocin could be due to a stress-related stimulation of the oxytocin- as well as of the gastric gastrin- and somatostatin-producing cells, occurring particularly during vaginal delivery. The significant inverse correlation found between fetal pH and the recorded hormone levels is consistent with this hypothesis.

Acid-Base Equilibrium↗

Catecholamine and blood pressure levels in paralysed preterm ventilated infants.

The effect of pancuronium administration on catecholamine levels and blood pressure was investigated. Noradrenaline levels prior to paralysis amongst infants fighting the ventilator were high, but were significantly reduced following treatment with pancuronium. There was no significant change in either blood pressure or adrenaline levels. Increasing peak inspiratory pressure (approx. 4 cmH2O) immediately prior to paralysis effectively prevented the hypoventilation previously associated with the administration of the first dose of pancuronium.

Blood Pressure↗

Somatostatin in the control of respiration.

Somatostatin has been found to induce apnoea when applied into the brain ventricular system (Fuxe et al. 1982, Härfstrand et al. 1985). The site of action of somatostatin was suggested to be in the dorsal respiratory neurons in the medulla oblongata of the rat (Fuxe et al. 1982) where high somatostatin-like immunoreactivity has been detected (Kalia et al. 1984a). In the present study we wanted to further localize the site(s) of action of somatostatin on respiration by microinjection of somatostatin into the medulla oblongata of the cats. We could not detect any inhibitory effect of somatostatin on respiration after microinjection into the nuclear complex of the solitary tract. On the other hand microinjection of somatostatin into the region of nucleus paragigantocellularis lateralis consistently caused apnoea. This finding further supports the idea that this structure functions as an integrative area of respiratory drive inputs.

Animals↗

Smoking exerts a ketogenic influence in diabetic pregnancy.

Acute cardiovascular and metabolic responses to the smoking of two cigarettes were studied in 12 normal and 7 diabetic women in the last trimester of pregnancy. When the responses to smoking were compared between the healthy and diabetic women no statistically significant difference was found except for 3-hydroxybutyric acid where diabetic women but not the normal patients reacted with a pronounced increase. It is concluded that smoking exerts a ketogenic influence in diabetic pregnancy.

Diabetic Ketoacidosis↗

Plasma catecholamine levels in preterm infants. Effect of birth asphyxia and Apgar score.

Catecholamine levels were measured in cord arterial blood from preterm infants. Relatively lower catecholamine levels were found in the preterm infants than in term infants, although no significant correlation was found between noradrenaline and adrenaline levels and either gestational age or birthweight. Significantly higher catecholamine levels were found after labour. Preterm females had significantly higher catecholamine levels than boys after asphyxia and tended also to have higher catecholamine levels without asphyxia, although not significant. Catecholamine levels were also significantly elevated in those infants with a low Apgar score (less than 7 at 5 min) and those who were acidotic (cord arterial pH less than 7.25). A good correlation was found between a low Apgar score and the presence of acidosis.

Apgar Score↗

The effect of non-nutritive sucking on plasma insulin, gastrin, and somatostatin levels in infants.

The aim of the present investigation was to study the effect of non-nutritive sucking on plasma levels of insulin, gastrin, and somatostatin in infants. These hormones were measured with radioimmunoassay in plasma collected from fullterm and preterm infants sucking a pacifier. In fullterm infants, sucking caused a significant increase of insulin levels from 13 +/- 10 microU/ml to 40 +/- 36 microU/ml and 21 +/- 17 microU/ml after 45 sec and 5 min respectively, from when the infants started sucking. A similar pattern was seen in preterm infants. In contrast, gastrin and somatostatin levels were not significantly affected. We suggest that sucking causes an activation of the vagal nerve, which results in the release of insulin. We also suggest that in infants, oral feeding is superior to bolus feeding, since in the latter case no vagal activation and consequently no release of hormones with anabolic properties occurs.

Gastrins↗

The epidemiology of sudden infant death syndrome and attacks of lifelessness in Sweden.

Infants who died showing the syndrome of sudden infant death (SIDS) and infants who survived attacks of lifelessness (AL) were examined in a prospective epidemiological multicentre study over 24 months covering close to 40% of all births in Sweden. Seventy SIDS cases and 34 cases of AL were observed, giving an incidence for SIDS of 0.94/1000 and for AL of 0.46/1000. This SIDS incidence is higher than that observed during the seventies. The boy/girl ratio was 1.4:1 for SIDS and 1.6:1 for AL. The age distribution for AL resembled that for SIDS. Similarities were also seen with regard to place of occurrence. Sixty per cent of the SIDS cases occurred during the daytime/evening. Twenty-nine per cent of the infants with AL had more than one apneic spell during the three-day-period around the attack, indicating a period of respiratory instability, but only 12% had such spells later on. None of the infants who had had AL died from SIDS. The possible relationship between AL and SIDS is discussed.

Age Factors↗

Role of the vagal afferents in substance P-induced respiratory responses in anaesthetized rabbits.

Since substance P (SP)-like immunoreactivity has been demonstrated in vagal sensory fibres of bronchopulmonary origin, it was considered of interest to (1) characterize the pattern of responses to SP injected into the pulmonary as well as the systemic arterial system, and (2) assess the types of vagal afferents that are affected by SP. Experiments were performed on 15 pentobarbital-anaesthetized, spontaneously breathing rabbits. Efferent phrenic nerve activity was monitored as an index of central respiratory neural output. Intra-atrial injections of SP into the pulmonary circulation (100 ng kg-1) increased the respiratory rate, and peak integrated phrenic amplitude by 47 +/- 8 and 40 +/- 4%, respectively, above the controls. In addition, SP elicited augmented breaths (ABs) within 2-3 s in 67% of the trials. In contrast to right atrial injections, no ABs and no significant changes in respiratory rate were observed in response to intra-aortic injections of SP (100 ng kg-1). Tidal phrenic activity rise after aortic injections of SP was significantly less as compared with right atrial administrations of SP. Since both routes of administration decreased the arterial blood pressure to the same extent, these respiratory responses were not likely secondary to cardiovascular changes. After administration of an SP antagonist (D-Arg-D-Trp7,9, Leu11, SP), respiratory responses to SP were significantly attenuated. Also, the rate of occurrence of ABs elicited by releasing the tracheal occlusions was reduced (control 95 vs. 14% SP antagonist). Bilateral vagotomy abolished the tachypnoeic response and reduced the magnitude of the phrenic nerve increments caused by right atrial injection of SP.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Respiratory and neuroendocrine responses of piglets to hypoxia during postnatal development.

Breathing response to 12% and 6% O2 in N2 (at isocapnia) was measured in anaesthetized piglets, 1-5 and 19-25 days old, before and after 3 mg kg-1 i.v. naltrexone. The degree of interaction between the anaesthetic 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 adrenalin. Whereas respiration in older animals was stimulated by hypoxia, young piglets had a biphasic response with a pronounced ventilatory decrease in response to severe hypoxia (6% O2/N2). In young animals there was a greater ventilatory response with naltrexone than without the drug, and the biphasic hypoxic response was ameliorated or reversed by naltrexone. Levels of adrenalin increased and those of encephalin, adenosine and noradrenaline tended to increase during hypoxia in the younger age group. Levels of adenosine showed significant increase when data from both age groups and levels of hypoxia were pooled. Combined with previously reported physiological evidence regarding adenosine in hypoxic depression, we conclude that the present results are compatible with a role of opioid peptides and adenosine in the early postnatal response to hypoxia.

Adenosine↗

Postnatal sensitivity of the peripheral chemoreceptors in newborn infants.

The peripheral chemoreflex was tested in healthy term infants by measuring the ventilatory response to 100% oxygen over 30 seconds. Minute ventilation did not change when studied two to six hours after birth. By contrast, at 2-6 days of age a mean decrease of 9.8% was noted, the difference between the groups being highly significant. There were no significant changes in respiratory rate. It is concluded that the chemoreflex is less active immediately after birth than it is a few days later, possibly due to a resetting of the sensitivity of the peripheral chemoreceptors from the fetal state, with its relatively low arterial oxygen tension to the higher postnatal concentrations.

Chemoreceptor Cells↗

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.

Apgar Score↗

Neuromodulators and respiratory control in the infant.

In this review some of the neuromodulators involved in respiration control are discussed with special regard to the newborn. The term neuromodulator is defined relatively widely herein. Various types of neuromodulators have been found to affect respiratory control. These effect are more pronounced in the fetus and the neonate than in the adult. A disturbed balance between excitatory and inhibitory neuromodulators is postulated as causing the instability of respiratory control often seen in infants.

Adenosine↗