PubMed Health⌕ Search

Biomedical subjects

H Lagercrantz

Publications and source records attributed to H Lagercrantz.

At least 163 records · Page 9Linked to original sources

Ventilatory and metabolic responses to acute hypoxia in infants assessed by transcutaneous gas monitoring.

Transcutaneous PO2, transcutaneous PCO2 and respiratory pattern were monitored during acute mild hypoxia (15% O2) in quiet sleep. Eighteen healthy infants were studied sequentially at 1-5 days, 4-8 weeks and 10-14 weeks of age. The transcutaneous PCO2 changes (delta PCO2) related to the transcutaneous PO2 fall, were used as an index of the total ventilatory and metabolic response during the test. This calculated index was related to the occurrence of arousal and periodic breathing. Transcutaneous PCO2 increased above control levels in infants 1-5 days old, decreased markedly in infants 4-8 weeks of age, and decreased slightly or remained unchanged in the 10-14 weeks old infants. The changes in response pattern were significant (P less than 0.006). These differences in response were not reflected in the lowest values of transcutaneous PO2 attained during the test. The lowest transcutaneous PO2 levels did not differ significantly between the age groups, indicating that the mechanisms maintaining PO2 during hypoxia may change during development. Periodic breathing was always associated with a decrease in transcutaneous PCO2 and in 8 out of 10 tests where it occurred it commenced at the lowest transcutaneous PCO2 level recorded. These results do not support the concept that periodic breathing is a sign of hypoventilation. Arousal was observed in less than half of the infants and was not related to the degree of hypoxaemia. We conclude that hypoxic arousal in infants may not be the important escape mechanism as suggested previously.

Arousal↗

Cardiovascular, metabolic and endocrine effects of chemical sympathectomy and of adrenal demedullation in fetal sheep.

A procedure in fetal sheep for causing peripheral sympathectomy by regular intravascular guanethidine sulphate administration and for causing adrenal demedullation by intragland injection of acid formalin is reported. Demedullation substantially removed adrenaline from the fetal circulation, but has a small effect only on noradrenaline. Plasma noradrenaline levels were depressed by 50% when demedullated fetuses were also subject to peripheral sympathectomy by guanethidine sulphate treatment. This provides some evidence that the paraganglia in the sheep fetus contributes to resting plasma catecholamines. Furthermore the ability of adrenal demedullation to increase markedly this pool of extra-adrenal chromaffin tissue indicates that in the fetus adrenal activity regulates the growth of these para-aortic bodies. In response to sympathectomy plasma vasopressin concentrations rose substantially, whilst adrenal demedullation caused a small rise. Demedullation and sympathectomy depressed fetal plasma glucose and elevated plasma cortisol. In both sympathectomised and adrenal demedullated fetuses resting heart rate and blood pressure was not depressed. However in those with a depleted peripheral nervous system periods of cardiovascular instability were apparent after 2-3 days of treatment with guanethidine sulphate. Hence there were regular episodes where fetal blood pressure and heart rate fell sharply followed 60-90s later by very large increases in blood pressure sustained for up to 10 min and associated with substantial production of plasma vasopressin and catecholamines. These results show that fine cardiovascular control in the fetus requires an intact sympathetic system as the endocrine system is too slow responding to effectively maintain reflex vascular control.

Adrenal Medulla↗

In vivo release of substance P in the nucleus tractus solitarii increases during hypoxia.

In vivo release of substance P (SP) was measured by microdialysis in the nucleus tractus solitarii (nTS) in adult cats. Small perfused semipermeable tubules (microdialysis probes) were implanted stereotaxically in the nTS, at the position of respiration-related neurons and perfused with artificial CSF. SP was determined by radioimmunoassay of the perfusate. Increased extracellular concentrations of SP-like immunoreactivity (SP-LI) were measured during hypoxia induced in artificially ventilated cats. In addition, a prolonged increase in the extracellular SP-LI concentration was encountered after cervical vagotomy. The results corroborate the suggestion that SP is a mediator of the central response to hypoxia.

Animals↗

Plasma catecholamines following nursing procedures in a neonatal ward.

Plasma catecholamines (CA) were determined in arterial blood from infants in a neonatal ward before and after various management procedures. Special care led to a 60% increase in plasma noradrenaline levels (P less than 0.02) whereas the adrenaline concentrations were not significantly affected. CA levels tended to be slightly higher after heel prick and gavage feeding than before, but the differences were not significant.

Blood Pressure↗

Ventilatory effect of an adenosine analogue in unanesthetized rabbits during development.

The effect of an adenosine analogue N6-L-(R-phenylisopropyl)adenosine (R-PIA) on respiration was studied in rabbit pups (1-8 days old). Respiration was monitored by a noninvasive barometric method during natural sleep. The adenosine analogue was given by an indwelling intraperitoneal catheter. R-PIA given in a dose of 0.1 mumol/kg (380 micrograms/kg) body wt caused a decrease of the ventilation. The respiratory decrease could be reversed or prevented by pretreatment with theophylline (10 mg/kg). R-PIA caused a considerably more pronounced effect in 1- to 3-day-old animals than in 8-day-old animals. This effect was seen both when the ambient temperature was held at 28 (P less than 0.01) and 32 degrees C (P less than 0.05). Determination of R-PIA receptors in whole brains of rabbit pups of various ages showed that R-PIA bound with higher affinity to membranes from newborn animals (Kd 0.53 nM) than older animals (Kd 0.7-1.26). Since adenosine is released during hypoxia, it may be involved in "hypoxic depression" of respiration in neonates and apnea of prematurity. This might also explain the potent therapeutic effect of the adenosine antagonist theophylline on recurrent apnea in preterm infants.

Adenosine↗

Beta-adrenoceptor function in white blood cells from newborn infants: no relation to plasma catecholamine levels.

The maturity of beta-adrenoceptors in newborn infants was studied in relation to the catecholamine surge during labor. Umbilical blood was collected at birth from 12 infants delivered vaginally and 13 infants delivered by elective cesarean section. Granulocytes and lymphocytes were isolated. Receptor numbers and binding affinity were determined in the granulocytes by incubation with 125I-iodohydroxybenzylpindolol. Receptor responsiveness was tested by assessing isoproterenol-induced cyclic AMP accumulation in lymphocytes. Significantly higher plasma noradrenaline, adrenaline, and dopamine concentrations were found in infants born vaginally (108; 8.9; 0.9 nmol/liter, liter, respectively, median values) as compared with those delivered by cesarean section (11.0; 2.4; 0.2 nmol/liter). No significant differences in beta-adrenoceptor binding sites (receptor number: 39.2 +/- 2.6 versus 44.7 +/- 5.9 fmol/mg protein and binding affinity: 66.6 +/- 7.8 versus 65.0 +/- 6.2 pM) or responsiveness (maximal isoprenaline induced cAMP formation 52.4 +/- 10.3 versus 40.6 +/- 8.9 pmol/10(6) cells) were found between the two groups of infants. Lymphocyte beta-adrenoceptor sensitivity was similar to that found in adults. The beta-adrenoceptors on whole blood cells seem to be mature at birth and have the same responsiveness as in adults. The higher catecholamine surge during vaginal delivery as compared to elective cesarean section does not seem to affect beta-adrenoceptor function. Our results do not support the idea that reduced beta-adrenoceptor function is the cause of the previously observed inappropriately small cardiovascular and metabolic responses to the exceptionally high plasma catecholamine concentrations at birth.

Binding Sites↗

Seasonal changes in blood lipids, adrenaline, noradrenaline, glucose and insulin in Norwegian reindeer.

Plasma concentrations of free fatty acids (FFA), glycerol, adrenaline, noradrenaline, glucose and insulin, as well as serum concentrations of triacylglycerols, total cholesterol and high density lipoprotein (HDL)-bound cholesterol, were measured at intervals during a I-year period in Norwegian reindeer. Free fatty acids and glycerol were high in January-March, low in April-July, and high again in August-September. Glucose was low in November-February and high but variable in March-October. Triacylglycerols, total and HDL-bound cholesterol were all low in November-March, but increasing in April and reaching a peak in August-September. Plasma noradrenaline and adrenaline did not change significantly throughout the year. Plasma insulin was low in October-April, increasing significantly from June-August/September. The seasonal changes in the serum concentrations of triacylglycerols, total and HDL-bound cholesterol, as well as the plasma concentration of glucose, coincided with the seasonal changes in food intake. Free fatty acids and, to some extent, glycerol were, in contrast, inversely related to feed intake. It is suggested that insulin may play an important role in the long-term regulation of fat mobilization, while the importance of catecholamines in this respect is questionable.

Animals↗

Some effects of substance P on central respiratory control in rabbit pups.

Respiratory effects of substance P (SP) have been studied in rabbit pups (I-30 days). Rabbits were either anaesthetized with urethane or decerebrated at mid-collicular level. Respiratory activity was measured with a pneumotachograph or in some cases as efferent phrenic nerve activity. SP applied to the exposed medulla oblongata from the dorsal side caused an increase of both tidal volume and respiratory frequency. The respiratory stimulation was more pronounced in decerebrate animals than in anesthetized ones. Moreover, this effect was most prominent in the youngest animals. A SP analogue (D-Arg1-D-Pro2, D-Trp7,9, Leu11)-SP was found to block the ventilatory effects of SP and to decrease the hypoxic response, while the hypercapnic response was preserved. The results suggest that SP is involved in the control of respiration, possibly mediating the hypoxic response, and that this role is more important in the neonatal period.

Age Factors↗

Alveolar hypoventilation treated with medroxyprogesterone.

Two children aged 1 and 20 months developed alveolar hypoventilation syndrome. They suffered severe apnoeic episodes and periodically required assisted ventilation. Their ventilatory response to carbon dioxide was lower than that of normal children and the transcutaneous oxygen tension during sleep was well below the normal range. Treatment with medroxyprogesterone acetate resulted in an improved response to carbon dioxide, and assisted ventilation was no longer needed. Oxygen and carbon dioxide tensions improved but were still slightly abnormal during sleep. There were no clinical side effects of treatment but one infant had slight pituitary suppression.

Carbon Dioxide↗

Post-mortem analyses of neuropeptides in brains from sudden infant death victims.

The causative factors underlying SIDS are still unknown, but in recent years much interest has been focused on the central ventilatory control system. In this study, peptides which are known to affect respiration were examined in brains from SIDS victims and controls. The levels of Met-enkephalin and substance P were measured in cortex, medulla oblongata, pons and hypothalamus. Substance P1-7, substance P C-terminal fragments, Met-enkephalin-Lys6 and neuropeptide Y (NPY) were estimated in medulla oblongata. The substance P levels in the medulla oblongata from the SIDS victims were significantly elevated compared with the controls. No change, however, was observed in the Met-enkephalin levels, but a tendency to higher levels in the youngest infants was noticed. As substance P and enkephalins have opposite effects on respiration, their relative concentrations were calculated in each individual sample. The ratio was significantly higher in the medulla oblongata from the SIDS victims. The levels of NPY, substance P1-7, C-terminal fragments of substance P and Met-enkephalin-Lys6 were similar in both groups. A significant correlation between the NPY levels and age was observed, however.

Age Factors↗

The relationship between circulating catecholamines and ST waveform in the fetal lamb electrocardiogram during hypoxia.

Previous studies from this laboratory have shown that changes in the ST waveform in the fetal electrocardiogram are a sign of fetal asphyxia. In the present study, seven chronically instrumented fetal lambs between 117 and 143 days' gestation were studied during 16 one-hour periods of maternally induced hypoxia. The aim was to test the hypothesis of a relationship between the concentration of circulating catecholamines and T-wave amplitude. The response to hypoxia was aged-dependent. Fetuses below 126 days of gestation did not react with electrocardiographic changes and output of epinephrine unless acidosis occurred. In more mature fetuses, hypoxia per se would induce a surge of epinephrine and changes in the ST waveform. Overall there was a strong correlation between the T/QRS ratio and the level of circulating epinephrine. During normoxia, epinephrine was undetectable (less than 0.1 nmol/L) in most fetuses; norepinephrine showed an increase at term. The analysis showed one fetus with chronic changes in the ST waveform (T/QRS ratio greater than 0.30) related to a marked increase in the plasma level of epinephrine in spite of normal blood gas values. These findings complement previous results in the acute and chronically instrumented fetal lamb and suggest that changes in the ST waveform expressed as T/QRS ratio identify a change to anaerobic myocardial metabolism mediated by beta-adrenergic stimulation.

Acidosis↗

Sympathoadrenal activity and peripheral blood flow after birth: comparison in infants delivered vaginally and by cesarean section.

The possible influence of sympathoadrenal activity on peripheral blood flow was studied. Limb blood flow was measured with venous occlusion plethysmography at 30 minutes, 2 hours, and 24 hours after birth in 24 healthy, full-term infants, of whom 14 were delivered by elective cesarean section. Mean arterial pressure was simultaneously measured noninvasively, and peripheral vascular resistance calculated. Umbilical artery blood at birth and peripheral venous blood at 2 and 24 hours were analyzed for concentrations of catecholamines and hematocrit. The limb blood flow was significantly lower at 30 minutes in the vaginally delivered infants compared with those delivered by cesarean section. There was a gradual increase in limb blood flow over the 24 hours in those delivered vaginally, whereas in the section group only small changes were observed. The peripheral vascular resistance was higher both at 30 minutes and at 2 hours in those delivered vaginally, which corresponded to the higher catecholamine concentrations at birth and at 2 hours in this group. Two hours after birth there was a significant correlation between noradrenaline levels and peripheral vascular resistance. The results indicate that the sympathoadrenal system influences peripheral circulation at birth and is important in the circulatory adaptation of the newborn infant.

Blood Pressure↗

Neonatal left ventricular performance after vaginal delivery and cesarean section under general or epidural anesthesia.

Left ventricular systolic time intervals, plasma norepinephrine concentration, hematocrit, and blood pressure were recorded in infants delivered vaginally and by cesarean section from mothers under epidural or general anesthesia. Each group comprised 12 infants. Left ventricular ejection time and the preejection period were longer in infants delivered vaginally, although the concentrations of norepinephrine found were greater than those found in the cesarean section groups. Hematocrit and blood pressure were unrelated to the mode of delivery or the anesthetic technique. The isovolumic contraction time, however, was significantly shorter after epidural anesthesia 15.6 +/- 7.6 msec (mean +/- 1 SD) than after general anesthesia 20.5 +/- 8.0 msec at 30 minutes (p less than 0.05), 14.8 +/- 6.2 msec, and 20.9 +/- 5.7 msec at 2 hours respectively (p less than 0.001). These differences in left ventricular dynamics are probably related to the effects of anesthetics that have traversed the placenta rather than to mode of delivery.

Anesthesia, Epidural↗