Journal of developmental physiology最新文献

We have examined the effects of fetal hypoxaemia, produced by reducing the percent oxygen in maternal inspired air, on fetal plasma concentrations of corticotrophin releasing hormone (CRH), adrenocorticotrophin (ACTH) and cortisol and determined the effects of an opioid receptor antagonist, naloxone on these responses. Hypoxaemia (fetal PO2, 15-18 mmHg) for 60 min provoked a significant (P < 0.05) increase in fetal plasma ACTH and cortisol concentrations at days 125-130 of pregnancy, but did not affect circulating CRH. There was no effect of naloxone administered either intravenously (1.25 mg bolus followed by a 2.5 mg/h continuous infusion for one hour; fetal body weight approximately 2.5 Kg) or via the lateral cerebral ventricle (50 micrograms bolus followed by a 100 micrograms/h infusion for one hour) on this pattern of ACTH and cortisol change nor on the lack of CRH response to hypoxaemia. We conclude that the increase in fetal ACTH and cortisol in response to acute hypoxaemia is not accompanied by an increase in systemic CRH concentrations, nor is the response dependent on short-term opioid regulation.

This study was undertaken in order to describe circulating glucose and cholecystokinin (CCK) concentrations in relation to the spontaneous feeding behavior of the human newborn infant. Eighty-three, healthy, 3-days-old infants were studied in connection with breast feeding. Blood samples from the infants were cross-sectionally collected before feeding, 5 and 10 min after the start of sucking, and after the infants had sucked ad libitum. Before feeding, the infants presented a typical "hunger behavior", which changed in connection with breast feeding into a pattern associated with satiety. A significant increase in the plasma CCK concentration was found, 5 min (P = 0.004) and 10 min (P = 0.02) after the start of sucking, as well as after feeding (P = 0.04). Furthermore, a positive correlation between the CCK concentration and the volume of ingested milk was found 10 min after the start of sucking, when 91% of of the volume of milk had been ingested; Rs = 0.51, n = 19, P < 0.02. However, no change was found in the glucose concentration in connection with breast feeding. It is concluded that CCK may be important as a satiety factor in the regulation of food intake in the newborn infant.

We investigated the role of cord occlusion in the initiation of breathing at birth using an extracorporeal membrane oxygenator system to control fetal blood gases independently of the placenta in 12 chronically instrumented fetal lambs. In group IA (n = 9; exp = 12) PaCO2 was kept constant (5.62 +/- 0.21 to 5.70 +/- 0.23 kPa) during cord occlusion. Group IB (n = 7; exp = 8) were cord occlusion experiments from group IA in which no fetal breathing movements had occurred; CO2 flow to the membrane was increased and fetal PaCO2 rose significantly (5.45 +/- 0.24 to 8.27 +/- 0.56 kPa). In group II (n = 7; exp = 12) PaCO2 was allowed to increase from 5.98 +/- 0.24 kPa to 8.09 +/- 0.48 kPa after cord occlusion. Within 5 min of cord occlusion, FBM did not occur in 11 out of 12 experiments in group IA or in 11 out of 12 experiments in group II. In contrast in group IB breathing did occur in 5 out of 8 experiments. When they occurred, fetal breathing movements were always associated with low voltage electrocortical activity. Our results do not support the hypothesis that the initiation of breathing within 5 minutes of birth is dependent on an inhibitory factor of placental origin. Furthermore these data suggest an association between the presence of breathing and a substantial rise in PaCO2.

The relative amount of regional cerebral oxygen transport was compared between different preterm infants by performing measurements of cerebral blood flow velocity, mean arterial blood pressure, whole blood viscosity and haemoglobin content for each individual. In addition the percentage of fetal haemoglobin was determined. On 25 occasions measurements of fetal haemoglobin and cerebral oxygen transport have been performed prior to and following a blood transfusion with adult red blood cells. Comparison of the data for cerebral oxygen transport suggests that the actual amount of cerebral oxygen transport is lowest at fetal haemoglobin levels below 30% and will increase progressively as soon as the percentage of fetal haemoglobin rises about 30%. Thus, at increasing fetal haemoglobin levels, cerebral haemodynamic mechanisms in the human neonate cause elevations of regional cerebral blood flow and oxygen transport. The found increase of cerebral blood flow and oxygen transport at high fetal haemoglobin levels will minimize the impeded dissociation and delivery of oxygen to brain tissues.

Although the administration of 100% O2 alone or combined with umbilical cord occlusion induces continuous breathing and arousal in the fetal sheep (Baier, Hasan, Cates, Hooper, Nowaczyk & Rigatto, 1990a), the individual contribution of O2 and cord occlusion to the response have not been determined. We hypothesized that if O2 is an important factor in the induction of continuous breathing, administration of O2 low enough (10%) to bring fetal arterial PO2 to about 20 torr while the fetus is breathing continuously should reverse these changes. Thus we subjected 12 chronically instrumented fetal sheep to 10% O2 for 10 minutes after the establishment of continuous breathing by O2 (4 fetuses; 137 +/- 1 days) or by O2 plus umbilical cord occlusion (8 fetuses; 134 +/- 1 days). Arterial PO2 decreased from about 250 torr to 20 torr during 10% O2. This induced a significant decrease in breathing output (EMGdi x f) related primarily to a decrease in frequency (f). In 3/5 experiments in 4 fetuses, with O2 alone, apnoea developed within 4 +/- 0.6 min; in 12/13 experiments in 8 fetuses, with added cord occlusion it developed at 5 +/- 0.6 min. With the decrease in PaO2, electrocortical activity (ECoG) switched from low to high-voltage within 6 minutes in 5/5 experiments (O2 alone) and in 11/13 (O2 plus cord occlusion). The findings suggest that umbilical cord occlusion alone is not sufficient to maintain breathing continuously and an increased PaO2 is needed. We speculate that in the fetus there is a vital link between PaO2, breathing and ECoG with low PaO2 inhibiting and high PaO2 favouring breathing and arousal.

We asked what effects hyperoxia may have on the metabolic response to cold of the newborn rat. Whole body gaseous metabolism (VO2 and VCO2) was measured in 2-day old rats by open flow respirometry at ambient temperatures (Tamb) between 40 and 20 degrees C, changed at a rate of 0.5 degrees C/min during normoxia and hyperoxia (100% O2 breathing). In normoxia, the thermoneutral range was very narrow, at Tamb = 33-35 degrees C. A decrease in Tamb at first stimulated VO2; a further drop in Tamb below 28 degrees C reduced metabolic rate. The metabolic response to cold was not sufficient to maintain body temperature (Tb). In hyperoxia average values of VO2 were above the normoxic values at all Tamb, but the difference was mostly apparent at low Tamb; at 20 degrees C, hyperoxic VO2 averaged 73% more than in normoxia. This metabolic increase determined a significant but small rise of Tb. We conclude that in the 2-days-old rat hyperoxia has a stimulatory effect on metabolism which is Tamb-dependent, being much more apparent in the cold. This supports the concept that the normoxic VO2 of the newborn is limited by the supply of O2. However, the fact that in the cold, even in hyperoxia, VO2 did not reach very high values, and Tb was not maintained, suggests that not only O2 availability, but also the rate of O2 utilization limits the aerobic metabolic response of the newborn.

Aminophylline, a methyl xanthine, has been used for many years in the treatment of apnea of prematurity and bronchospasm. Aminophylline relaxes smooth muscle through several proposed mechanisms. We hypothesized that aminophylline might be effective in relaxing preconstricted pulmonary vascular smooth muscle and would be ideally suited for clinical trial in babies with pulmonary hypertension. To test this hypothesis, the haemodynamic response of chronically instrumented newborn lambs to injections of heat-killed Group B beta-hemolytic Streptococcus (GBS) and leukotriene (LT) D4, potent pulmonary vasoconstrictors was compared before and after pretreatment with a clinically therapeutic dose of intravenous aminophylline. GBS (10(9)cfu) significantly increased pulmonary arterial pressure 130%. LTD4 (1.0 microgram/kg) significantly increased pulmonary arterial pressure 142% and systemic arterial pressure 23% and decreased cardiac output 47%. Aminophylline did not significantly affect the baseline variables or alter the pulmonary or systemic haemodynamic response to either stimuli. Therefore, it is unlikely that aminophylline will be clinically useful in the treatment of babies with persistent pulmonary hypertension whose etiology is infectious or leukotriene-mediated.

Spontaneous, long lasting epochs of myometrial contractility, contractures, occur throughout the majority of pregnancy in sheep. Contractures are temporally related to a switch in fetal electroencephalogram (ECoG) patterns from low to high voltage. In late gestation, fetal ECoG increases in voltage. We have previously suggested that contractures may influence fetal ECoG maturation. In the present study, we hypothesized that a sustained increase in the frequency of myometrial contractures in pregnant sheep at 120-140 days gestation would accelerate maturation of the fetal ECoG. Five pregnant ewes were pulsed with oxytocin 600 microU.kg-1.min-1 intravenously for five minutes in every 30 minutes from 127.8 +/- 1.5 days gestational age for a minimum of six days. Six control ewes received pulses of saline. Fetuses of all eleven ewes were instrumented with bilateral electrodes to record fetal ECoG and nuchal muscle activity. Fetal high voltage (HV) ECoG increased in amplitude in both groups but the rate of increase was faster in the fetuses of ewes receiving oxytocin. There were no differences between the two groups in the duration of HV ECoG. The percentage increase in the amount of time the fetal nuchal muscles were active compared with the baseline day before infusion was only significant in the oxytocin infused group on the first day of oxytocin infusion. These findings support the hypothesis that myometrial activity during pregnancy has the capacity to influence fetal neural development.

Cardiac myosin heavy chain (MHC) expression undergoes an ontogenetic transition from beta to alpha MHC isoforms. Although thyroid hormone plays a role in this change, the timing of the events suggests the participation of other factors. Using a new, denaturing SDS-PAGE procedure that cleanly resolves the beta and alpha heavy chains, we have assessed the role of beta-adrenergic stimulation on this transition in fetal and neonatal rat hearts. In control animals at embryonic day 20, less than 15% of the MHC was the alpha-form, and the proportion increased to approximately 35% by postnatal day 1 and to 80% by postnatal day 8. Although catecholamine levels rise abruptly at birth, and cyclic AMP levels increase the expression of alpha-MHC in vitro, neither premature beta-adrenergic stimulation (maternal treatment with terbutaline on embryonic days 17, 18 and 19) nor continuous prenatal blockade of beta-receptors (maternal propranolol infusions from embryonic day 7 onward) influenced the developmental profile. Because beta-receptors in fetal and neonatal heart are functionally linked to adenylate cyclase, and cyclic AMP has been shown to promote the expression of alpha-MHC, the lack of effect of terbutaline or propranolol suggests that activation of adenylate cyclase through fetal cardiac beta-receptors is not sufficient to mediate the switchover without participation of other factors, such as thyroid or steroid hormones, or hypoxia.

Experiments were conducted in 12 chronically-catheterized pregnant sheep to examine the effect of prolonged hypoxaemia secondary to the restriction of uterine blood flow on fetal oxygen consumption. Surgery was performed at 115 days gestation to place a teflon vascular occluder around the maternal common internal iliac artery and for insertion of vascular catheters. Following a 5-day recovery period, uterine blood flow was reduced in 6 animals for 24 hours and in 6 animals, the occluder was not adjusted. Fetal arterial PO2 decreased from 19.9 +/- 2.0 mmHg to 12.8 +/- 2.0 mmHg and 11.0 +/- 2.0 mmHg at 1 and 24 hours respectively in the experimental group and did not change the control group. Fetal pH decreased from 7.34 +/- 0.01 to 7.25 +/- 0.03 and 7.29 +/- 0.02 at 1 and 24 hours of hypoxaemia respectively. Fetal arterial lactate concentrations remained elevated throughout the experimental period with maximum concentrations of 6.6 +/- 2.1 mmol/l being present at 4 hours compared to 1.3 +/- 0.2 mmol/l during the control period. Umbilical blood flow increased from 186 +/- 19 ml/min/kg to 251 +/- 39 ml/min/kg at 1 h of hypoxaemia and returned to 191 +/- 21 ml/min/kg at 24 h. In association with the progressive fall in oxygen delivery to the fetus, oxygen extraction increased from 0.33 +/- 0.04 to 0.43 +/- 0.04 and 0.54 +/- 0.05 at 1 and 24 hours, respectively. Overall oxygen consumption by the fetus remained unchanged from control values.(ABSTRACT TRUNCATED AT 250 WORDS)