Pregnant rats were fed to appetite on diets containing 6, 9, 12 or 18% protein and the fetuses were delivered at 20 days. Compared with the 18% protein diet (7.4 MJ), there was a significant increase in food and energy intake in the rats on the 9% (8.7 MJ) and 12% (8.4 MJ) diets, but not on the 6% (7.4 MJ) diet. The efficiency with which the dietary energy was used for weight gain was reduced on the 6, 9 and 12% diets compared with the 18% diet. The trend towards a decrease in the number of viable fetuses and an increase in the number of resorptions on the 9% and 6% diets did not reach statistical significance. The placental weight was not different to the 18% group (520 mg) on the 12% diet (540 mg), but was significantly increased on the 9% diet (590 mg) and significantly decreased on the 6% diet (510 mg). Fetal weight was greatest on the 12% diet (1.81 g) and significantly decreased on the 9% diet (1.71 g). The fetal:placental ratio, around 3.3 for the 18 and 6% diets, was significantly increased on the 12% diet (3.7) and significantly decreased to 2.9 on the 9% diet. After adjusting for the effect of the fetal position in the uterine horn, the number of pups per litter and an estimate of the number of failed implantations the effect of diet on placental weight was no longer statistically significant, but the effect of dietary protein on fetal weight was more significant statistically, with little change overall on the fetal:placental ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
This study was designed to determine the effects of hypothyroidism during late fetal life in pigs on (1) the perinatal pattern of plasma levels of thyroxine (TT4), total 3,5,3'-triiodothyronine (TT3) and free T3 (FT3), and liver 5'-deiodinase activity, and (2) the early postnatal development of thermoregulation. Fetal hypothyroidism (test animals) was induced by feeding the sow a high glucosinolate rapeseed diet. Plasma levels of thyroid hormones, thyroid gland weights and liver 5'-deiodinase activity of control animals increased during late gestation (P < 0.01). The early postnatal period was characterized by a surge in thyroid hormone levels during the first 6 h (P < 0.05), followed by a transient decrease at 12 h and a second rise by 24 h after birth. This surge was much higher (P < 0.01) for TT3 than for TT4, but liver 5'-deiodinase activity did not change during the first 24 h of life. Fetal hypothyroidism was characterized by lower plasma levels of thyroid hormones (P < 0.05), and lower hepatic 5'-deiodinase activities (P < 0.01) than in control fetuses at 110 d of gestation. During the first 6 h of life, test pigs had lower levels of TT4 (P < 0.05) but exhibited a greater postnatal surge in TT3 and FT3 (P < 0.05) than did the controls. The minimal and summit metabolism of the control pigs increased markedly (P < 0.01) during the first 2 d of life, without any significant change in thermal body conductance, suggesting that this age-related improvement in thermoregulation was due to the development of the ability to produce heat.(ABSTRACT TRUNCATED AT 250 WORDS)
In the course of studying developmental changes of induction and maintenance of ventricular fibrillation in canine pups, we have documented that at about the third week of age, hearts reach a critical point where ventricular fibrillation may become both inducible and sustainable, thus forming the basis for cardiac arrhythmic death. Since age-related variations of cardiac mass may account for these findings, this study was conducted to systematically investigate the role of changing heart mass on the induction and maintenance of ventricular fibrillation in the canine heart, during the early postnatal development. Repetitive determinations of ventricular fibrillation threshold and individual incidence of spontaneous defibrillation were obtained in 87 puppies 1-6 weeks old, from litters of varied body size breeds, studied at weekly intervals. Overall, ventricular fibrillation threshold correlated positively with ventricular weight (VFTmA = 3.30 + 1.27 Vwtg, r = 0.71). However the slopes were steeper and correlations were stronger for the first, second and sixth week and nonsignificant in the fourth and fifth weeks. The ventricular fibrillation to ventricular weight ratio also varied with age (P < 0.01). Spontaneous defibrillation occurred at least once in 68 of the puppies (78%). In general, spontaneous defibrillation was more likely to occur in hearts weighing less than 9 grams (P < 0.01), but the overall correlation of the decreasing defibrillation incidence to increasing weight was weak (SDF % = 48.6-0.90 Vwtg, r = 0.106). Spontaneous defibrillation was not observed at any age or weight in two litters, totaling 9 puppies.(ABSTRACT TRUNCATED AT 250 WORDS)
The peripheral arterial chemoreceptor response to hypoxemia in the fetus is predominantly cardiovascular, invoking a fall in heart rate and a variable change in blood pressure. No quantifiable measure of chemoreceptor activity has yet been described in the intact fetus. We described the course, quantified the overall response, and defined the reproducibility of the heart rate response to acute hypoxemia in 22 late-term unanesthetized fetal sheep. Fetuses were chronically instrumented and studied between 1-6 days postoperatively. Acute hypoxemia was induced by occluding a balloon cuff around the common hypogastric artery. We performed 151 occlusions, starting at an initial saturation of 66 +/- 11%, decreasing saturation by 8-50%. Soon after balloon inflation, arterial oxygen saturation fell, followed by a decrease in heart rate. We calculated delta HR/delta sat, the fall in heart rate divided by the fall in saturation. Multiple linear regression analysis showed a sensitive chemoreflex, delta HR/delta sat averaging 2.5 +/- 1.2 bpm.%saturation-1. Initial saturation did not alter the first phase of the response (from the onset of the decrease in oxygen saturation to the onset of the decrease in oxygen saturation to the onset of the decrease in heart rate), but it did increase the overall response (delta HR/delta sat) when saturation was less than 65%. After adjusting in the lower range of initial saturations to that predicted at 65%, delta HR/delta sat was very reproducible within animals, with intra-animal variance being only 7% of inter-animal variance.(ABSTRACT TRUNCATED AT 250 WORDS)
The energy cost of growth includes two components: the energy stored in new tissues and the energy expended in all energy requiring steps associated with nutrient intake and net tissue accretion. Most of the energy expended in growth is accounted for by the energy cost of tissue anabolism: peptide bonds, lipogenesis, substrate transport, etc. However, to the extent that additional work is required of the heart and lungs for growth-related increases in O2 and CO2 transport, increased energy is also expended in cardiorespiratory work. Indirect estimates of these costs can be gained by examining the effects of diet and weight gain on heart rate and respiratory frequency. We studied 66 healthy low birth weight infants, mean study weight = 2010 g, fed constant intakes of protein (2.25-3.9 g/kg per day) and energy (100-150 kcal/kg per day). These diets led to rates of weight gain ranging from 13.9 to 21.7 g/kg per day, among the diet groups. Bi-weekly 6-h assessments of energy expenditure, heart rate, respiratory frequency and state of sleep were made after full enteral intake was achieved. After adjustment of heart rate for the effect of postnatal age, heart rate during active sleep was related to weight gain (y = 0.97 x + 144, r2 = 0.15), nitrogen-energy ratio of the diet (y = 5.9 x + 139,2 r2 = 0.22), and energy expenditure (y = 0.53 x + 129, r2 = 0.13). Multiple regression analysis revealed that age-adjusted heart rate during active and quiet sleep was significantly related to a combination of the same three variables (r2 = 0.31).(ABSTRACT TRUNCATED AT 250 WORDS)
Glucocorticoids have been shown to accelerate the development of blood coagulation in the fetal lamb (Kisker, Robillard & Bohlken, 1983). The current studies examine the influence of high levels of triiodothyronine (T3) on the development of blood coagulation in the fetal lamb. Eight twin fetal lambs were studied during the last trimester of pregnancy (109-138 days gestation) using chronically placed arterial and venous catheters for infusion of T3 and withdrawal of blood samples. One fetus of each twin was infused intravenously with T3 at a constant rate of 0.6 mug T3/0.4 ml/h for 48 h. The other twin was infused with 5% dextrose at 0.4 ml/h for 48 h. Blood samples for measuring PT, PTT, TT, fibrinogen, factors II, V, VII, VIII, IX, X, XI and XII were obtained prior to and at the completion of the infusions. The results were analyzed for differences between the samples from paired control and T3 treated animals. Factor V significantly decreased in the T3 infused animals from 51.2% +/- 12.5% to 44.8% +/- 13.8% (P=0.038). Factor VII also decreased in the treated animals 57.8% +/- 20% to 43.6% +/- 10.8%, but the changes were not statistically significant (P=0.06). Factor XII significantly increased in the treated animals from 37% +/- 10.5% to 45% +/- 13.7% (P=0.004). High levels of T3 in third trimester fetal lambs are accompanied by a moderate decrease in factor V and an increase in factor XII activity.
The release of arachidonic acid and inositol polyphosphates from permeabilised myocytes derived from guinea pig uterus has been studied. Both are enhanced by free calcium at 100 nM and 10 microM and particularly by 50 microM GTP gamma S. To distinguish between the contributions of phospholipase C and A2 to the release of arachidonic acid the phospholipase C inhibitor neomycin was used. At 1 and 10 mM, but not at 0.1 mM, neomycin caused effective inhibition of inositol polyphosphate release of over 95%. Neomycin (1 mM) also reversed GTP gamma S-stimulated, but not calcium-stimulated release of arachidonic acid. This action was reflected in changes in [3H]arachidonic acid labelling of the membrane phosphatidylinositol and phosphatidylcholine pools, which were depressed by over 20% on the addition of 50 microM GTP gamma S, an effect completely reversed by 1 mM neomycin. The effects of neomycin were much more pronounced on inositol phosphate than on arachidonic acid release. The ability of 1 mM neomycin to inhibit arachidonic acid release was reversed by addition of 1 microM phorbol 12-myristate 13-acetate, implying a role for protein kinase C activation in stimulation of arachidonic acid release. Measurement of phospholipase A2 activity with 1-stearoyl 2-arachidonoyl phosphatidylcholine as exogenous substrate demonstrated the ability of 1 and 10 mM neomycin to inhibit the enzyme particularly when it was maximally activated with 1 mM free calcium.(ABSTRACT TRUNCATED AT 250 WORDS)
Allylestrenol or benzpyrene, given either between the 15th and 19th days of fetal life or from birth to the postnatal 7th day, caused dramatic decrease in the sexual activity of adult female rats. Allylestrenol, given in fetal life, resulted in a profound increase in the sexual activity of male rats. Given in newborn conditions, a decrease of sexual activity was caused by the same chemical. Considering, that one of the molecules has importance in medical practice and the other is an environmental pollutant, the experiments forecast the probability of modification in the sexual behaviour of human adults.
To investigate the ontogeny of a circadian rhythm in body temperature, we performed 24-h temperature measurements at six postnatal ages in ten newborn lambs reared independently of their ewes. At 18 to 48 h of age, a significant time-of-day variation in body temperature was found, the variation achieving a peak between 5.00 pm and 6.00 pm. Over the next two weeks, this time-of-day variation disappeared, reappearing at 18 days of age, although the phase had shifted such that the peak temperature was achieved between 8.00 am and 9.00 am. At 26 days of age, the time-of-day variation in body temperature was still present, maintaining the same phase relationship as at 18 days of age. It is possible that the significant time-of-day variation observed in the two oldest groups is due to the emergence of a discernable circadian rhythm in body temperature entrained to the light-dark cycle during the second or third week of life, whereas the time-of-day variation observed in the 18 to 48-h old is due to residual effects of entrainment to maternal zeitgebers. We speculate that the lack of any observable time-of-day variation in the 4, 6 and 11 days-old lambs may denote the presence of no rhythm or possibly a free-running rhythm in body temperature in subjects not yet able to entrain to photic zeitgebers.
Cerebral oxidative metabolism and associated circulatory responses were determined in 14 unanesthetized fetal sheep near term, during a normoxic control period and subsequently, during four days of prolonged and graded hypoxemia induced by progressively lowering maternal inspired oxygen concentration with 1-2% CO2 added; first day 18%, second day 16%, third day 12-14%, fourth day 10-12%. Preductal arterial and sagittal vein blood samples were analyzed for oxygen content, blood gas tensions and pH. Regional blood flow was measured with a microsphere technique. Cerebral blood flow increased in a stepwise manner with the graded reduction in fetal arterial O2 saturation and continued to be well predicted by blood gas and metabolic alterations, with no adaptive change evident. Cerebral oxidative metabolism remained little changed with chronically induced hypoxemia until arterial O2 saturation was less than 30% and with fetal acidemia evident when decreased to 70% of normoxic control values. Whether the decrease in oxidative metabolism by the brain at this time represents an adaptive response whereby growth and functional alterations lead to a decrease in nonessential energy utilization or rather a pathological change, remains to be determined.
Experiments were done on seven lambs between the ages of 18 and 24 days to investigate the effects of sleep on systemic and coronary hemodynamics. Each lamb was anesthetized and instrumented for recordings of electrocorticogram, electro-oculogram and nuchal electromyograms, and for measurements of cardiac output and coronary blood flow as well as systemic arterial blood pressure and arterial-, mixed-venous- and coronary-sinus- hemoglobin oxygen saturations. No sooner than three days after surgery, measurements were made during periods of quiet wakefulness (QW), quiet sleep (QS) and active sleep (AS) at an ambient temperature of 25 degrees C. Cardiac output and heart rate were decreased during AS compared to QW and QS. A significant increase in systemic vascular resistance during AS prevented more than a slight decrease in systemic arterial blood pressure. Coronary blood flow decreased during AS compared to QW and QS. Furthermore, myocardial work as estimated from the product of systolic blood pressure and heart rate decreased during AS compared to QW and QS as did myocardial oxygen consumption and myocardial oxygen transport. Transient hypertensive phases--defined as transient increases in mean blood pressure of greater than 15 mmHg above the mean blood pressure for a period of AS--occurred during eight of 13 periods of AS in four of the seven animals. These transient hypertensive phases were caused primarily by an increase in systemic vascular resistance; surprisingly, coronary vascular resistance also increased at this time when estimated myocardial work was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Present study tried to evaluate the influence of different diets (low- and high-salt, bicarbonate) administered during prenatal period on body and organ weights of newborn Dahl salt-sensitive (DS) and salt-resistant (DR) rats. Blood pressure of DR dams was not influenced by dietary loading but it was significantly increased by high-salt diet in DS rats. Blood pressure of all DS dams was higher when compared to the respective DR rats. There were significant negative correlations between mean arterial pressure of DS (but not DR) dams and body weight of newborns in all dietary groups. Litter sizes were comparable in all groups studied. High-salt diet increased body weight and relative heart weight of newborns of both genotypes. On the other hand, the influence of bicarbonate diet on body weight was more pronounced in DS pups whereas the effect on relative heart weight was seen only in DR newborns. The relative heart and kidney weights were significantly higher and relative liver weight significantly lower in newborns of DR dams when compared to those of DS dams irrespective of mother's diet. There was a tendency in all organs of DS newborns to contain less water in comparison with respective DR pups. It should be noted that in newborns of both genotypes bicarbonate diet lowered relative DNA content more than relative protein content. In conclusion, high-salt and bicarbonate diets exert dissimilar effects on prenatal body and organ development in Dahl rats.
Fluid secretion by the fetal pulmonary epithelium is thought to be important for normal lung development yet little is known about factors regulating its production. As prostaglandins are synthesized in human fetal lung and stimulate secretion in a variety of epithelia, we investigated the effect of prostaglandins E2 and F2a (PGE2 and PGF2 alpha) on ion transport and fluid secretion in cultured first trimester human fetal lung tissue explants. We used conventional microelectrodes to continuously record the transepithelial potential difference (psi t). The addition of either PGE2 or PGF2 alpha to the bathing solution significantly hyperpolarized the lumen negative psi t and the subsequent addition of bumetanide, an inhibitor of chloride secretion in other systems, depolarized psi t by approximately 60% suggesting chloride transport contributed to the voltage. To assess whether this acute change in psi t represented stimulation of fluid secretion, we measured the change in luminal area of the explants after a 24-h exposure to prostaglandins. Both PGE2 and PGF2 alpha caused significant increases in the mean % luminal area of the explants compared with control tissues consistent with a stimulation of lung fluid secretion. Cultured lung tissue explants produced prostaglandins E2 and F2 alpha as assessed by radioimmunoassay of cell culture media samples and both prostaglandins stimulated cAMP accumulation in the explants. These findings show that lung fluid secretion in the human fetal pulmonary epithelium can be stimulated by prostaglandins. This effect may be mediated through cAMP dependent pathways. Prostaglandins may play a physiologic role in regulation of fetal lung fluid transport in vivo.
A comparative chronological study (from 1 to 33 days post partum) was performed to establish the capacity for nonshivering thermogenesis (NST) in rats born and reared at 28 degrees C and at 16 degrees C. The resting metabolism measured at 33 degrees C was higher in the 16 degrees C rats than in the 28 degrees C rats from the 3rd day. When expressed per weight or per surface area units it was higher in 16 degrees C pups than in 28 degrees C pups until the end of the 3rd week. In fact the resting metabolism was significantly proportional to different powers of weight (W0.67 at 16 degrees C and W0.75 at 28 degrees C) during the suckling period. At birth, respiratory quotient (RQ) was the same in both groups (0.70); it increased slowly to the end of the 3rd week (about 0.80). During the 3rd week RQ was lower in 16 degrees C rats than in 28 degrees C animals. This indicates that 16 degrees C rats are more dependent on the milk supplied by their mother. After weaning there were no differences in RQ values (0.90). Rectal temperature was low in both groups on day 1 (about 32 degrees C). It increased until weaning when it stabilized at 37 degrees C. From day 1 to day 18, it was significantly lower in cold reared rats. The capacity for NST was measured by investigating the effect of an injection of norepinephrine (NE) on the metabolic rate at 33 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
Umbilical cord occlusion in the presence of adequate oxygenation induces continuous breathing and arousal in the chronic unanesthetized fetal sheep preparation. The mechanism responsible for this is unknown. We hypothesized that if a placental factor is responsible for the inhibition of breathing in the fetus, the administration of a placental extract while the fetus is breathing continuously after cord occlusion should reverse these changes. Thus, at about 10 min after the induction of continuous breathing by cord occlusion, we administered a placental extract and three subfractions separated by ultrafiltration to 14 chronically instrumented fetal sheep at 133 +/- 1 day gestation. The Krebs solution in which the placental extract was prepared was used as control. Within two minutes of the infusion of the whole placental extract in the carotid artery of the fetus, breathing output (integral of EMGdi x f) diminished in all experiments and was completely abolished in 15/17 (88%). Krebs solution had no effect on breathing. The infusion of subfractions of different molecular weight showed that the inhibition was primarily related to the subfraction between 3.5 and 10 kD. There were no significant changes in blood gas tensions, pH, blood pressure, and heart rate associated with the infusions of the extracts. The ECoG switched from low to high voltage in the majority of the experiments using whole extract and the subfraction 3.5 to 10 kD. These findings suggest that a placental factor, probably a peptide with a molecular weight between 3.5 and 10 kD, inhibits breathing in fetal life.
This study examines the effects of altering the prenatal maternal metabolic and hormonal environment via chronic cold exposure of under-fed ewes on developmental changes in breathing control of developing lambs. Breathing frequency and timing were measured during non rapid-eye-movement (non-REM) sleep in lambs born from either shorn or unshorn ewes after being maintained for at least one hour at warm (28-19 degrees C) and cool (14-5 degrees C) ambient temperatures at 1, 4, 14 and 30 days of age. Breathing frequency and oxygen consumption were significantly higher in 1 day old lambs born from shorn ewes compared with those lambs born from unshorn ewes, at both warm and cool ambient temperatures. In the shorn group breathing frequency decreased between 1 and 4 days of age and continued decreasing upto 30 days of age, during which period inspiratory and to a greater extent expiratory time, lengthened. Laryngeal "braking" of expiratory airflow was observed in more than 50% of lambs born from shorn ewes during non-REM sleep in the warm at 4, 14 and 30 days of age, and in the cold at 14 and 30 days of age. In contrast, lambs born from unshorn ewes showed no change in breathing frequency between 1 and 4 days of age, but a decrease was observed between 4 and 14 days of age, whilst laryngeal "braking" of expiratory airflow was rarely observed at any age.(ABSTRACT TRUNCATED AT 250 WORDS)
The effects of protein kinase C activation on phospholipase A2 and phospholipase C activity in permeabilised cultured myometrial cells from guinea pig uterus have been studied. Phospholipase A2 activity was followed by measurement of [3H]arachidonic acid release from [3H]arachidonic acid-prelabelled membrane lipids. [3H]Arachidonic acid release was stimulated by Ca2+ at 1-10 microM and by GTP gamma S at 1 microM to 1 mM in the presence of 10 microM Ca2+. The activation by calcium was enhanced 89.5 +/- 12.7% (P < 0.01) in the presence of 1 microM phorbol 12-myristate 13-acetate (PMA) and that by 1 microM GTP gamma S by 65.4 +/- 4.4% (P < 0.001). The PMA enhancement of arachidonic acid release was completely blocked by 3 microM staurosporine. Phospholipase C activation was followed by measurement of [3H]inositol polyphosphate production from [3H]inositol-prelabelled membrane lipids. This was stimulated by Ca2+ at 0.1 and 10 microM and by 1 and 50 microM GTP gamma S. PMA at 1 microM caused a consistent reduction in the extent of Ca2+ and GTP gamma S-stimulated inositol polyphosphate production and 3 microM reversed the inhibitory action of PMA. The data are consistent with arachidonic acid release in permeabilised myometrial cells from guinea pigs reflecting in large part phospholipase A2 activation and with that pathway being stimulated by protein kinase C activation. They are also consistent with protein kinase C activation causing reduction in phospholipase C pathways in uterine myocytes, at least as measured by inositol polyphosphate release.
To make the chick embryo accessible to electrophysiological measurements in its mesonephric kidney during the period between embryonic days (e.d.) 5 and 10, a special "chick-embryo-incubation bath" was constructed. It consists of an aerated chamber covering the egg and maintaining the gas exchange across the shell, and of a warmed reservoir of the incubation medium, into which the embryo is pulled out of the egg through a window in the shell. The two compartments are separated with a rubber membrane tightly fitting to the edges of the shell-window. The incubation medium contains a modified Krebs-Henseleit-Ringer solution and anesthetic Tricaine (Sigma). Access to the mesonephric nephrons is achieved by surgical excision of the body wall on the right side performed at e.d. 5. On average only about 35 percent of the operated embryos survive till the third day after surgery but during the next two days a mortality rate recedes to zero. The tolerance of short-term survival of embryos placed in the incubation bath was tested for up to 4 1/2 h. It was very good in embryos of age 5 to 7 e.d. as assessed by a steady heart rate and the presence of arterio-venous differences. A modified differential amplifier containing circuits for frequency compensation of the two channels was used for high-fidelity registration of voltage changes in the embryonic nephron with a single double-barrel microelectrode.
The aim of this study was to document arterial blood pressure wave forms at two sites along the arterial tree of the neonate: in the radial and posterior tibial arteries. Using a high-fidelity catheter tip-transducer system, peripheral arterial blood pressure wave forms in 26 critically newborn infants were studied. In 14 infants the radial artery and in 12 infants the posterior tibial artery was cannulated. Radial artery blood pressure waves resembled those of proximal aortic rather than those of the radial artery in adults. Quantitative analysis of the waves was performed to reassure this finding. Blood pressure waves obtained from posterior tibial artery resembled those of femoral artery rather than those of posterior tibial artery waves in adults. We conclude that radial and posterior tibial artery wave forms in neonates appear to have a central appearance. This phenomenon might be explained by the close proximity of the radial and posterior tibial artery to the central aorta and femoral artery respectively, due to the small and short limbs of the neonate. The finding allows an "easy central pressure look" at both ends of the neonatal aorta.
We hypothesized that exposure of neonatal swine to chronic alveolar hypoxia (CH) would cause increased PVR, blunt acute hypoxic vasoconstriction, and increase VA/Q mismatch. After exposure to either normobaric alveolar hypoxia (FIO2 = 0.10) or room air for 2 weeks, animals were anesthetized and ventilated first with room air and then with hypoxic gas (FIO2 = 0.12). PVR, and pressure-flow (P/Q) relations were measured between 15-100% of baseline cardiac output. VA/Q matching was measured by the multiple inert gas elimination technique. During room air breathing, the mean PVR and P/Q slope in the CH animals was significantly greater than in the control (C) animals. P/Q intercepts were similar and near the origin for both groups. The absolute PVR and P/Q slope were greater for CH compared to C animals during acute alveolar hypoxia. The fractional increase in PVR and P/Q slope in the response to acute hypoxia was similar for both groups. PaO2, intrapulmonary shunt, and SDQp (an index of VA/Q heterogeneity) were similar for both groups. We conclude that CH in neonatal swine causes pulmonary hypertension, but does not attenuate acute hypoxic pulmonary vasoconstriction, nor VA/Q matching.
