Time-dependent tracheal deformation in fetal, neonatal, and adult rabbits

Sequential magnitude and the rate of change in tracheal mechanics after application of intermittent positive pressure (IPP), and the time constant, tau, of this deformation were determined in fetal (21 and 27 days gestation), neonatal (term, 31 days gestation) and adult rabbits. In vitro tracheal mechanics were determined by liquid plethysmography before and after IPP, (25 cm H2O at 30 cycles/min) of 20, 40, 60, and 120 min duration. A sequential decrease in tracheal compliance was documented at all ages. This was associated with increased values of tau as the maturational age advanced. Further, the rate of tracheal deformation was 0.008 cm H2O min-1 at 21 days gestation compared to 0.00025 cm H2O min-1 at adulthood. The decrease in rate of deformation was related to the gestational maturity and duration of IPP. The rate of deformation, as predicted by calculated deformation time constants, appears to be a function of structural elastic and viscoelastic properties of the trachea as well as the duration and magnitude of applied pressure. The deformation time constant may be defined as a useful index to predict the rate of airway deformation. Utilizing the rabbit model, this provides a measure of comparing barotrauma with different modes of ventilation in preterms.     

Glycine site of the excitatory amino acid N-methyl-D-aspartate receptor in neonatal and adult brain.

The N-methyl-D-aspartate (NMDA) receptor complex in brain is a glutamate receptor subtype with several recognition sites including a glycine site that is able to modulate and activate allosterically the receptor. This receptor may be important in the regulation of developmental synaptic plasticity. The release of glutamate and consequent overstimulation of NMDA receptors that follows hypoxia-ischaemia leads to brain damage. Brain tissue obtained at necropsy was studied in a total of 16 term infants aged less than 1 week to 22 weeks and in four adults aged from 66 to 84 years. Glycine sites were determined in brain sections by the binding of the selective ligand [3H]5,7-dichloro-kynurenic acid and measured by autoradiography. In infant brains the amount of binding to the glycine site was higher in temporal cortex and hippocampus than in basal ganglia and was also higher than in comparable areas of adult brain. The amount of glycine site binding in infant cortex increased with postnatal age. The data suggest that infant brain acquires a relatively high density of NMDA receptors in temporal lobe due to postnatal proliferation of glutamatergic synapses. These findings have therapeutic implications as drugs that reduce NMDA receptor function by blocking the glycine modulatory site would be pertinent to preventing brain damage after hypoxia-ischaemia.     

新生甲减仔鼠心肌甲状腺激素受体mRNA的表达

先天性甲状腺功能减低症（克汀病）患儿常伴发严重的心脏损害,形成甲减性心脏病,说明甲状腺激素缺乏可能影响心肌的正常发育,目前关于甲状腺激素缺乏对心肌发育影响的相关研究甚少。甲状腺激素通过甲状腺激素受体（thyroid hormone receptors,TR）调节目的基因的转录,从而发挥其正常生理功能,据此本研究采用实时荧光定量PCR（Real time fluorescence quantitationPCR,FQ-PCR）方法定量分析了正常和甲减新生仔鼠心肌中TRmRNA的表达差异。     

Maternal beta-adrenergic tocolysis and neonatal bilirubin production

The potential for beta-adrenergic drugs to increase total bilirubin formation via cyclic adenosine monophosphate-mediated stimulation of hepatic microsomal heme oxygenase in the human neonate was evaluated. The pulmonary excretion rate of endogenously produced carbon monoxide (VeCO), an index of total bilirubin formation (TBF), was measured in 18 preterm neonates whose mothers received beta-adrenergic drugs for tocolysis and in 18 preterm neonates whose mothers were untreated. The mean VeCO of the neonates in the former group (17.2 +/- 7.3 microL/kg/hr) was the same as that in the latter group (17.4 +/- 6.2 microL/kg/hr); both values were elevated when compared with the mean VeCO of 20 term newborns (13.9 +/- 3.5 microL/kg/hr). Our findings indicate that TBF is not significantly increased in neonates whose mothers received beta-adrenergic drugs before delivery.     

Altered maternal thyroid function: fetal and neonatal myocardial metabolism

The influence of the maternal thyroid status on the fetal and neonatal myocardial protein, carbohydrate and lipid metabolism was studied in rats. The neonates born of hypothyroid mothers could not survive beyond 8 days after birth. The offsprings born of hypothyroid mothers showed growth retardation, decreased level of heart mitochondrial protein, reduced myocardial free fatty acid (FFA) oxidation at birth and afterwards, low glucose oxidation by the heart at later fetal stages, and afterwards, despite low heart glycogen reserve, glucose oxidation was high. The offsprings born of hyperthyroid mothers showed stimulation in overall growth, increased myocardial FFA oxidation and increased 14C-glucose incorporation into glycogen as well as increased myocardial glucose oxidation during fetal stages. Results indicate that maternal thyroid hormones play an important role in the metabolic control of fetuses and neonates.     

Chronic bradykinin receptor blockade modulates neonatal renal function

Recent data indicate that bradykinin participates in the regulation of neonatal glomerular function and also acts as a growth regulator during renal development. The aim of the present study was to investigate the involvement of bradykinin in the maturation of renal function. Bradykinin beta2-receptors of newborn rabbits were inhibited for 4 days by Hoe 140. The animals were treated with 300 microg/kg s.c. Hoe 140 (group Hoe, n = 8) or 0.9% NaCl (group control, n = 8) twice daily. Clearance studies were performed in anesthetized rabbits at the age of 8-9 days. Bradykinin receptor blockade did not impair kidney growth, as demonstrated by similar kidney weights in the two groups, nor did it influence blood pressure. Renal blood flow was higher, while renal vascular resistance and filtration fraction were lower in Hoe 140-treated rabbits. No difference in glomerular filtration rate was observed. The unexpectedly higher renal perfusion observed in group Hoe cannot be explained by the blockade of the known vasodilator and trophic effect of bradykinin. Our results indicate that in intact kallikrein-kinin system is necessary for the normal functional development of the kidney.     

Role of ECMO in neonatal myocardial infarction.

A neonate with myocardial infarction who failed to respond to conventional treatment was supported by extracorporeal membrane oxygenation (ECMO). Severe mitral valve regurgitation necessitated mitral valve replacement while receiving ECMO following which the infant was successfully weaned. ECMO should be considered for potentially treatable causes of catastrophic heart failure.     

Glycine site of the excitatory amino acid N-methyl-D-aspartate receptor in neonatal and adult brain

The N-methyl-D-aspartate (NMDA) receptor complex in brain is a glutamate receptor subtype with several recognition sites including a glycine site that is able to modulate and activate allosterically the receptor. This receptor may be important in the regulation of developmental synaptic plasticity. The release of glutamate and consequent overstimulation of NMDA receptors that follows hypoxia-ischaemia leads to brain damage. Brain tissue obtained at necropsy was studied in a total of 16 term infants aged less than 1 week to 22 weeks and in four adults aged from 66 to 84 years. Glycine sites were determined in brain sections by the binding of the selective ligand [3H]5,7-dichloro-kynurenic acid and measured by autoradiography. In infant brains the amount of binding to the glycine site was higher in temporal cortex and hippocampus than in basal ganglia and was also higher than in comparable areas of adult brain. The amount of glycine site binding in infant cortex increased with postnatal age. The data suggest that infant brain acquires a relatively high density of NMDA receptors in temporal lobe due to postnatal proliferation of glutamatergic synapses. These findings have therapeutic implications as drugs that reduce NMDA receptor function by blocking the glycine modulatory site would be pertinent to preventing brain damage after hypoxia-ischaemia.     

Phototherapy and neonatal liver function.

Two groups of 'healthy' full-term infants with hyperbilirubinemia exposed to phototherapy for 72 h demonstrated no significant change in serum glutamic pyruvic transaminase (SGPT), isocitric dehydrogenase (SICD), alkaline phosphatase (SAP), heat stable alkaline phosphatase (HSAP), total protein and albumin values; these values were similar to those of a comparable group of control infants without hyperbilirubinemia. The bilirubin levels, however, decreased significantly during this period. In a separate group of full-term infants with hyperbilirubinemia, the bromsulphalein (BSP) test before and after 72 h of phototherapy also demonstrated no signficant alteration; the results were comparable to a control group of infants. Phototherapy, even for a duration of 72 h apparently does not seem to affect liver function in infants with hyperbilirubinemia.     

Short-term malnutrition in neonatal rabbits. I. Brush border enzymes

Seventy-two hour starvation in neonatal rabbits was studied. Fasted animals received no feeds, only water every 8 h for 72 h. Fed animals were suckled by the dam. There was no difference in birth weight, serum albumin, blood urea nitrogen, electrolytes, or urine specific gravity between fed and fasted animals. Weight at 72 hr was less in fasted (p less than 0.01) than fed rabbits. Serum cortisol (p less than 0.05) and corticosterone (p less than 0.01) levels were higher in the fasted group. Proximal and distal small bowel homogenates had less DNA and protein (p less than 0.01) in the fasted group, but the protein/DNA ratio was the same in the proximal and distal small bowel homogenates from both groups. Sucrase (E.C.3.2.1.26) specific activity was significantly increased in proximal small bowel homogenates from the fasted group (p less than 0.01) but was the same in distal small bowel homogenates from both groups. Sucrase total activity per proximal segment was the same in fed and fasted animals but was significantly less per segment in distal small bowel homogenates from fasted animals. Alkaline phosphatase (E.C.3.1.3) total and specific activity was decreased in proximal (p less than 0.01) and distal (p less than 0.05) small bowel homogenates from the fasted group. Lactase (E.C.3.2.1.23) total activity was decreased in proximal and distal (p less than 0.01) small bowel homogenates from the fasted group but lactase specific activity was unchanged. Thus, a brief period of malnutrition in neonatal animals can result in a variety of regional functional changes in the gastrointestinal mucosa.     

ATP-sensitive potassium channels in neonatal and adult rabbit ventricular myocytes.

The properties of the ATP-sensitive potassium (KATP) current were studied in freshly isolated rabbit ventricular myocytes using the patch clamp technique. Removing ATP from the bath (intracellular) solution activated a large K+ conductance in patches from neonatal cells with properties similar to those of KATP channels in other preparations. In membrane patches from neonatal ventricular myocytes, the density of KATP channels was higher than the density of inwardly rectifying K+ channels and the mean patch KATP current was approximately 10 times that of the inwardly rectifying K+ current, at a patch membrane potential of -60 mV. Glibenclamide (10 microM) in the bath solution decreased the number of functional KATP channels, the open-state probability, and the mean patch membrane current. The single-channel conductance of the KATP channel was dependent on the external K+ concentration, and the relationship between channel conductance and external K+ concentration was fit by an exponential equation. In addition, the voltage dependence, channel density, and open-state probability of this channel were compared between neonatal and adult isolated ventricular myocytes. The single-channel conductance and channel density of the KATP channel in neonatal myocytes were significantly smaller than in adult cells. These results suggest that age-related changes occur in the properties of KATP channels.     

Comparative actin polymerization in neonatal and adult bovine neutrophils in vitro.

Neutrophils rely on active reorganization of the cytoskeleton during movement, and functional deficiencies in the cytoskeletal elements may result in impaired neutrophil-mediated host defense. We have compared and quantitated actin polymerization in neonatal (< or = 48 h old) and adult bovine peripheral-blood polymorphonuclear leukocytes (PMN) using fluorescence flow cytometry. Baseline filamentous actin (F-actin) content of neonatal and adult PMN at time zero differed slightly but were not statistically different (p > 0.05). F-actin content of recombinant human C5a (10(-7) M)-stimulated neonatal PMN increased rapidly within 10 s of stimulation to 59.0% over baseline, then declined. F-actin in adult recombinant human C5a-stimulated PMN continued to increase for 30 s and was elevated 87.3% over baseline before subsequently declining. When stimulated with zymosan-activated bovine serum (10%), neonatal (120.7% increase) and adult PMN (115.1% increase) had similar profiles with no significant differences, and both groups reached peak F-actin levels at 30 s after stimulation. Neonatal PMN stimulated with platelet-activating factor (10(-6) M) attained peak F-actin values at 10 s (72.0% increase over baseline), but actin rapidly depolymerized by 30 s poststimulation (reduced to 29.0% increase). Adult PMN stimulated by platelet-activating factor also attained peak values by 10 s (97.6% increase over baseline), but in contrast to neonatal PMN the F-actin remained elevated at 30 s in the adult PMN (still increased 79.5%; p < 0.0.5 compared to neonatal F-actin).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of increased intracranial pressure on blood pressure, heart rate, respiration and catecholamine levels in neonatal and adult rabbits

The effect of increased intracranial pressure (ICP) on heart rate, respiratory rate and blood pressure was measured in 2-day-old and adult rabbits. Neonates and adults exhibited the Cushing reflex with hypertension, bradycardia and decreased respirations when exposed to elevated ICP. Adult animals had a lower threshold of response to elevated ICP, implying a more sensitive adrenergic response compared to neonates. Although control levels of epinephrine and norepinephrine were higher in neonates compared to adults, the ratio of maximum concentration during increased ICP to control concentration was higher in adults (27.0 for epinephrine and 25.2 for norepinephrine in adults: 3.5 for epinephrine and 2.93 for norepinephrine in neonates). Injection of epinephrine was used to induce a maximal sympathetic response in both groups of rabbits studied. In adults, the cardiovascular response was the same after injection of epinephrine or after increasing ICP. In neonates, the blood pressure rise after injection of epinephrine was significantly higher (p less than 0.05) than the blood pressure rise after increasing ICP. The results demonstrate an immature adrenomedullary axis in neonates who have higher resting levels of catecholamines with a relatively smaller increase in catecholamines in response to stress when compared to adults.     

Pulmonary aeration after unilateral fetal ligation of pulmonary artery in neonatal rabbits.

When the pulmonary artery was ligated at the gestational age of 30 days, 9 out of the 17 rabbit fetuses had vital lungs and in 7 of these the lungs were aerated after breathing for 15 min to 1 h. Ligation before this gestational age caused necrotic lungs in all 13 rabbit fetuses. On the basis of this we can conclude that the bronchial circulation is not sufficient to ensure vitality of the fetal lung and the pulmonary circulation does not play a major role in the primary aeration of the lungs at birth.     

Characterization of the beta-adrenergic receptor in isolated human fetal lung type II cells.

Functioning of the beta-adrenergic response system is important for successful transition of the neonate from fetal life to breathing air. We characterized the beta-adrenergic receptors on human fetal lung type II cells, the cell type responsible for many pulmonary responses sensitive to beta-adrenergic stimulation. Type II cells were isolated from human fetal lung explants, and membrane particulates prepared from these cells were used for radioligand binding studies. 125I-iodocyanopindolol, a specific beta-adrenergic antagonist, bound to a single class of saturable, high-affinity binding sites on type II cell membranes with a receptor concentration of 78 +/- 9 fmol receptor/mg membrane protein, a kd of 79 +/- 18 nM, and 958 +/- 120 receptors per cell. Binding was stereoselective with l-propranolol binding with higher affinity than the inactive d-isomer. The binding site had the characteristics of a beta 2-adrenergic receptor. The order of potency of beta-adrenergic agonists was isoproterenol greater than epinephrine much greater than norepinephrine. The beta 2-selective antagonist ICI 118,551 competed for a single class of high-affinity sites. Agonist binding affinity was reduced in the presence of guanyl nucleotides, consistent with receptors coupled to guanine nucleotide binding proteins. beta-Adrenergic agonists also stimulated adenylyl cyclase in these membrane preparations. 125I-iodocyanopindolol binding to membranes prepared from human fetal lung fibroblasts indicated fewer receptors (404 +/- 68) than were present on type II cells. Work by others has suggested a difference in lung function and lung beta-adrenergic receptor concentration between males and females.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of smoking in pregnancy on neonatal lung function.

AIMS: To assess the effects of smoking during pregnancy on lung mechanics and lung volumes in the immediate neonatal period, before infants are exposed to passive smoking. METHODS: Lung function tests were carried out within 72 hours of delivery in infants born to 100 non-smoking and 189 smoking mothers. Lung growth was assessed by plethysmography and lung mechanics using the single breath occlusion technique and oesophageal balloon/pneumotachography. Antenatal maternal serum cotinine values were obtained from 133 mothers. RESULTS: Smoking was associated with a significant reduction in birthweight (mean 256 g, 95% CI 0.164 to 0.392), and length (mean 1.26 cm, 95% CI 0.48 to 2.00). Lung volume was not reduced when related to weight. Smoking was associated with a highly significant reduction in static compliance (Crs). This effect remained significant after relating Crs to weight and lung volume. Regression analyses showed that the Crs association was limited to the boys. Smoking was associated with a small but significant reduction in respiratory system conductance (Grs) (single breath occlusion technique) and total pulmonary conductance (Gp). These associations were limited to girls. CONCLUSIONS: Smoking in pregnancy reduces static compliance in boys and conductance in girls. There was no evidence that maternal smoking adversely affected fetal lung growth.     

Crying vital capacity. Measurement of neonatal lung function.

Serial measurements of crying vital capacity (CVC), expressed as ml/cm chest circumference, were made by reverse plethysmography during the first 2 weeks of life. Clinically normal babies born at term by elective caesarean section had a smaller mean CVC in the first 2 weeks of life compared with clinically normal term babies born vaginally. In contrast, no significant difference was shown between the mean CVC in term babies born vaginally and those born by urgent caesarean section. Clinically normal term babies born by caesarean section (elective and urgent) had a smaller mean percentage rise of CVC in the first 24 hours of life and a significant delayed rise of CVC from 24-48 hours compared with those born vaginally. Clinically normal preterm babies born vaginally had a smaller mean CVC in the first 2 weeks of life compared with term babies born vaginally, and were characterized by a significant rise of CVC from 5-10 days. Babies with hyaline membrane disease (HMD) had a smaller CVC in the first 2 weeks of life compared with clinically normal preterm babies. Babies of various gestational ages with transient tachypnoea (TT) had a smaller mean CVC in the first 2 weeks of life compared with clinically normal term babies, but a similar mean CVC in the first 72 hours of life compared with clinically normal preterm babies. At each postnatal age the mean CVC of babies with HMD was less than the corresponding mean in babies with TT. All babies with TT had a rise in CVC from 24-48 hours, whereas CVC fell in all babies with HMD except one during this period. CVC is a simple, safe, rapid, and noninvasive test of neonatal lung function, and is a valuable aid to other methods of assessing pulmonary function in the neonate with respiratory distress.