Oxytocin-induced labor augments IL-1beta-stimulated lung fluid absorption in fetal guinea pig lungs

We tested the hypothesis that oxytocin-induced labor augmented IL-1beta-induced/-stimulated lung fluid absorption in preterm guinea pig fetuses. IL-1beta was administered subcutaneously daily to timed-pregnant guinea pigs for 3 days with and without simultaneous cortisol synthesis inhibition by metyrapone. At day 3, oxytocin was administered, and fetuses were delivered by abdominal hysterotomy at 61 and by oxytocin-induced birth at 68 days gestation. Delivered fetuses were instilled with isosmolar 5% albumin into the lungs, and lung fluid movement was measured over 1 h by mass balance. Lung fluid absorption was induced in 61-day and stimulated in 68-day gestation lungs by IL-1beta. Labor induction by oxytocin augmented IL-1beta-induced/-stimulated lung fluid absorption. Metyrapone pretreatment did not affect oxytocin-induced/-stimulated lung fluid absorption, while completely blocking IL-1beta-induced/-stimulated fluid absorption. Fetal lung fluid absorption, when present, was always propranolol and amiloride sensitive, suggesting that beta-adrenoceptor stimulation and amiloride-sensitive sodium channels were critical for fluid absorption. Epithelial sodium channel and Na-K-ATPase subunit expressions were both increased by IL-1beta, but not further by oxytocin. Our results indicate that IL-1beta release into the maternal blood circulation positively affects lung maturation due to the IL-1beta-induced release of cortisol and thus prepares the lungs for the epinephrine surge associated with labor.     

Ca(2+)-dependent stimulation of alveolar fluid clearance in near-term fetal guinea pigs

We investigated the importance of changes in intracellular Ca(2+) concentration ([Ca(2+)](i)) for amiloride-sensitive alveolar fluid clearance (AFC) in late-gestational guinea pigs. Fetal guinea pigs of 61, 68, and 69 days (term) gestation were investigated under normal conditions and after oxytocin-induced preterm labor. AFC or alveolar fluid secretion was measured using an impermeable tracer technique. At 61 days gestation there was net secretion of fluid into the lungs, and at birth the lungs cleared 49 +/- 7% of the instilled fluid volume over 1 h. Induction of preterm labor with oxytocin induced AFC at 61 days gestation. When present, AFC was inhibited or reversed to net fluid secretion by amiloride (10(-3) M). Inhibition of membrane Ca(2+) channels by verapamil (10(-4) M) or depletion of intracellular Ca(2+) by thapsigargin (10(-5) M) reduced AFC when net AFC was evident. Amiloride lacked an inhibitory effect on AFC when instilled with verapamil or thapsigargin. The results indicate that AFC via amiloride-sensitive pathways develops during late gestation, and that inducing preterm labor precociously may activate such pathways. Our results suggest that Ca(2+) may act as a second messenger in mediating catecholamine-stimulated AFC.     

IL-1beta stimulates alveolar fluid absorption in fetal guinea pig lungs via the hypothalamus-pituitary-adrenal gland axis

We tested the hypothesis that interleukin (IL)-1beta-induced cortisol synthesis stimulates alveolar fluid clearance in preterm fetuses. IL-1beta was administered subcutaneously daily to timed-pregnant guinea pigs for 3 days with and without simultaneous cortisol synthesis inhibition by metyrapone. Fetuses were obtained by abdominal hysterotomy at 61 and 68 days gestation and instilled with isosmolar 5% albumin in the lungs, and alveolar fluid movement was measured over 1 h from the change in alveolar protein concentration. Alveolar fluid clearance was induced at 61 days gestation and stimulated at 68 days gestation by IL-1beta, which both were attenuated by cortisol synthesis inhibition. Plasma ACTH and cortisol concentrations were increased by IL-1beta at both gestational ages, and metyrapone reduced cortisol concentrations. IL-1beta was mostly low or undetectable in both fetal and maternal blood. Prenatal alveolar fluid clearance, when present as well as IL-1beta induced, was always propranolol and amiloride sensitive, suggesting that beta-adrenoceptor stimulation and amiloride-sensitive Na+ channels were critical for fluid absorption. IL-1beta increased lung beta-adrenoceptor density at gestation day 61, and cortisol synthesis inhibition attenuated the increased beta-adrenoceptor density. Epithelial Na+ channel and Na+-K+-ATPase subunit expressions were both increased by IL-1beta and attenuated by cortisol synthesis inhibition. These results may explain why babies delivered preterm after intrauterine inflammation have a reduced risk of developing severe respiratory distress.     

Distal air space epithelial fluid clearance in near-term rat fetuses is fast and requires endogenous catecholamines

Knowledge about the conversion of the epithelium in the distal air spaces of the lung from secretion to absorption is imperative to the understanding of postnatal lung development; little such information is available in rats. Distal air space fluid clearance was therefore measured in 21- to 22-day gestation rat fetuses and newborn (40 h) rats. Distal air space fluid clearance was measured from the increase in (131)I-albumin concentration in an isosmolar, physiological solution instilled into the developing lungs. There was no net fluid movement across the distal air space epithelium in the lungs of 21-day gestation fetuses. Twenty-four hours later, distal air space fluid was cleared at a rapid rate in the 22-day gestation fetuses. Within the first 40 h after birth, the rate rapidly declined to adult levels. The high distal air space fluid clearance at 22 days gestation and at 40 h after birth was mediated by beta-adrenergic receptors as demonstrated by elevated plasma epinephrine levels and inhibition by propranolol. Interestingly, the elevated distal air space fluid clearance in the 22-day gestation fetuses was only minimally amiloride sensitive; however, amiloride sensitivity increased over the first 40 h after birth. In conclusion, these studies demonstrate that 1) rapid rates of net alveolar fluid clearance occur late in gestation in the rat and 2) this clearance is driven by elevations of endogenous epinephrine.     

Effect of tracheostomy on lung development in fetal lambs

The effects of fetal tracheostomy on lung development in lambs have been investigated. Seven ewes, all with twin fetuses, were given a general anesthetic. One fetus in each set of twins was tracheostomized and the other fetus was sham operated (117-122 days gestation). The fetuses were delivered by cesarean section between 137 and 140 days gestation. Fetal tracheostomy decreased lung weight and volume, altered DNA concentration and the structural development of the acinus, and decreased lung distensibility. However, tissue and airway saturated phosphatidylcholine and lung stability during deflation were not significantly affected by fetal tracheostomy. It seems that tracheostomy in fetal lambs alters lung growth but does not affect the formation or release of surfactant. These data support the hypothesis that lung volume is actively maintained and lung growth promoted by the secretion of lung fluid against the resistance of the upper airway in fetal lambs.     

Role of primary and secondary maternal viremia in transplacental guinea pig cytomegalovirus transfer.

The modulation of the outcome of intrauterine guinea pig cytomegalovirus (GPCMV) infection by maternal viremia was investigated in the guinea pig model. Virus assay and in situ hybridization were used to study GPCMV infection of maternal blood, placentas, and fetuses following inoculation of pregnant guinea pigs by the subcutaneous, intracardiac, or intranasal route. Animals were inoculated in early gestation and were evaluated every 7 to 10 days throughout pregnancy. Although placental and fetal infections occurred in all groups examined, transfer of GPCMV to placentas and fetuses was most efficient in mothers inoculated subcutaneously. Primary viremia was followed by virus clearance from blood and by an episode of secondary viremia in the three groups of mothers examined. Placental and fetal infections in animals infected subcutaneously or intracardially were first detected at the time of primary viremia, persisted throughout gestation, and increased during secondary viremia. In contrast, placental and fetal infections in animals inoculated intranasally were demonstrated primarily during secondary viremia. Fetal infection was detected in all mothers with detectable primary and secondary viremia but in only 33% of mothers that experienced only primary viremia. These results suggest that secondary maternal viremia is associated with increased placental and fetal GPCMV infections.     

Impaired cortical processing of inspiratory loads in children with chronic respiratory defects

Background

We tested the hypothesis that maternal interleukin-1β (IL-1β) pretreatment and induction of fetal cortisol synthesis activates MAP kinases and thereby affects lung fluid absorption in preterm guinea pigs.

Methods

IL-1β was administered subcutaneously daily to timed-pregnant guinea pigs for three days. Fetuses were obtained by abdominal hysterotomy and instilled with isosmolar 5% albumin into the lungs and lung fluid movement was measured over 1 h by mass balance. MAP kinase expression was measured by western blot.

Results

Lung fluid absorption was induced at 61 days (D) gestation and stimulated at 68D gestation by IL-1β. Maternal IL-1β pretreatment upregulated ERK and upstream MEK expression at both 61 and 68D gestation, albeit being much more pronounced at 61D gestation. U0126 instillation completely blocked IL-1β-induced lung fluid absorption as well as IL-1β-induced/stimulated ERK expression. Cortisol synthesis inhibition by metyrapone attenuated ERK expression and lung fluid absorption in IL-1β-pretreated fetal lungs. JNK expression after maternal IL-1β pretreatment remained unaffected at either gestation age.

Conclusion

These data implicate the ERK MAP kinase pathway as being important for IL-1β induction/stimulation of lung fluid absorption in fetal guinea pigs.     

Effects of norepinephrine on lung liquid production by in vitro lungs from fetal guinea pigs

Lungs from near-term fetal guinea pigs (61 +/- 2 days of gestation) were supported in vitro for 3 h; lung liquid production was monitored by a dye dilution method. Untreated control preparations produced fluid at 1.38 +/- 0.30 mL x kg(-1) body weight x h(-1), with no significant change (ANOVA; regression analysis); those given 1.24 x 10(-9) or 1.24 x 10(-8) M norepinephrine during the middle hour showed no significant change, but those given concentrations between 5.24 x 10(-8) and 1.24 x 10(-5) M all showed significant reductions or fluid reabsorption (based on 42 fetuses). The responses showed a linear relationship with the log concentration (r = 0.97). They appeared to involve alpha-adrenoreceptors, since responses to 10(-7) M norepinephrine were unaffected by 10(-6) M propranolol, but those to 10(-7) and 1.24 x 10(-6) M norepinephrine were abolished by 10(-6) and 1.78 x 10(-5) M phentolamine, respectively (based on 48 fetuses). Activation was through alpha2-adrenoreceptors, since responses to 10(-7) and 10(-5) M norepinephrine were abolished by 10(-4) M yohimbine, but not by 10(-5) M prazosin (based on 60 fetuses). The results show that norepinephrine is able to reduce lung liquid production when at plasma levels present at birth, and that it can produce reabsorption; unlike epinephrine, there was no reduction in responses at high concentrations. This work reintroduces a neglected factor, norepinephrine, into possible controls of lung liquid reabsorption, and opens up the potential for neural controls.     

Pharmacokinetics of ethanol and its metabolite, acetaldehyde, and fetolethality in the third-trimester pregnant guinea pig for oral administration of acute, multiple-dose ethanol

The pharmacokinetics of ethanol and its metabolite, acetaldehyde, were determined in the third-trimester pregnant guinea pig (56-59 days gestation) for oral intubation of four doses of 1 g ethanol/kg maternal body weight, administered at 1-h intervals. Animals (n = 4-7) were sacrificed at each of selected times during the 26-h study. Ethanol and acetaldehyde concentrations were determined by headspace gas-liquid chromatography. The maternal and fetal blood ethanol concentration-time curves were virtually superimposable, which indicated unimpeded bidirectional placental transfer of ethanol in the maternal-fetal unit. The blood and brain ethanol concentrations were similar in each of the maternal and fetal compartments during the study, which indicated rapid equilibrium distribution of ethanol. There was accumulation of ethanol in the amniotic fluid resulting in higher ethanol concentration compared with maternal and fetal blood during the elimination phase, which indicated that the amniotic fluid may serve as a reservoir for ethanol in utero. Acetaldehyde was measurable in all the biological fluids and tissues at concentrations that were at least 1,000-fold less than the respective ethanol concentrations and were variable. There was ethanol-induced fetolethality that was delayed and variable among animals, and was 55% at 23 h. At this time interval, the ethanol concentrations in maternal blood and brain, fetal brain, and amniotic fluid were 35- to 53-fold greater and the acetaldehyde concentrations in maternal blood and fetal brain were four- to five-fold higher in the animals with dead fetuses compared with the guinea pigs with live litters. These data indicated that decreased ethanol elimination from the maternal-fetal unit was related temporally to the fetolethality.     

Subacute inhalation of cigarette smoke by pregnant and lactating rodents: AHH changes in perinatal tissues

To study the transplacental acquisition of tobacco smoke products and the effects on fetal tissue enzymes, pregnant rats, guinea pigs, and hamsters were exposed to freshly generated cigarette smoke via a nose-only inhalation system on a daily basis through the latter one-third (guinea pigs) or latter half (rats, hamsters) of the gestational period. Following euthanasia on the day of parturition, microsomal aryl hydrocarbon hydroxylase (AHH) activities were determined in the lungs, livers, and kidneys of both dams and fetuses. The possible acquisition of tobacco smoke products via the milk was studied by exposing lactating dams to cigarette smoke daily for either 4 or 14 days (rats), 4 or 7 days (guinea pigs), or 10 days (hamsters), with analysis of tissues from the euthanized pups for AHH. Pups were also exposed directly (nose only) to cigarette smoke. In the treated pregnant and lactating rat, maternal pulmonary, hepatic, and renal AHH was significantly increased but only fetal lung and the liver of 14-day-old pups showed a marked induction of AHH activity. In the pregnant and lactating guinea pig, only the pulmonary and renal AHH activities were increased following exposure, whereas in the fetuses and nursing pups, none of the tissue AHH activities was significantly altered by exposure. In the pregnant and lactating hamster, only the pulmonary AHH was increased following exposure to cigarette smoke, whereas the activity in fetal and pup tissues remained unchanged from the levels observed in control animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies on the growth of the fetal guinea pig. Changes in plasma hormone concentration during normal and abnormal growth

The endocrine changes associated with fetal growth retardation caused by unilateral uterine artery ligation of guinea pigs at day 30 of pregnancy were studied. Plasma hormone levels in fetuses that, about 20 or 30 days later, were 35-50% of normal size were measured by radioimmunoassay. The small fetuses were severely hypoglycaemic and hypoinsulinaemic; both showing close correlation and relationship to the degree of growth retardation. Plasma thyroid and cortisol and concentrations were much lower than normal and that glucagon and androstenedione were much higher. Plasma growth hormone level appeared to be unaffected by growth retardation. The developmental changes in glucagon and thyroid hormone concentrations were consistent with a delay in the timing of prenatal events in growth-retarded fetuses. However the late cortisol rise, although somewhat blunted, still occurred at 58-60 in the small fetal guinea pigs.     

Effects of phrenic nerve section on the respiratory system of fetal lambs

We investigated the effects of phrenic nerve section (PNS) on the respiratory system of fetal lambs. Seven ewes, three of which had twin fetuses, were given a general anesthetic. The thoracic phrenic nerves were cut in two singleton fetuses and in one fetus in each set of twins (116-121 days); two singleton fetuses and one fetus in each set of twins underwent the same procedure except for PNS. Fetal arterial blood pressure, heart rate, and arterial pH and blood gas tensions were the same in both groups. Phrenic nerve section eliminated fetal breathing movements and decreased airway fluid volume, lung weight, and total lung DNA (P less than 0.05). However, PNS did not affect production of tracheal fluid or percent dry weight of the lungs. Furthermore, PNS did not affect the concentration of saturated phosphatidylcholine in the lung or its flux in tracheal fluid. We conclude that PNS in fetal lambs retards lung growth but does not affect tracheal fluid production or formation and release of surfactant.     

Lack of amiloride-sensitive transport across alveolar and respiratory epithelium of iNOS(-/-) mice in vivo

The extent to which endogenously generated nitric oxide alters Na(+) transport across the mammalian alveolar epithelium in vivo has not been documented. Herein we measured alveolar fluid clearance and nasal potential differences in mice lacking the inducible form of nitric oxide synthase [iNOS; iNOS(-/-)] and their corresponding wild-type controls [iNOS(+/+)]. Alveolar fluid clearance values in iNOS(+/+) and iNOS(-/-) anesthetized mice with normal oxygenation and acid-base balance were ~30% of instilled fluid/30 min. In both groups of mice, fluid absorption was dependent on vectorial Na(+) movement. Amiloride (1.5 mM) decreased alveolar fluid clearance in iNOS(+/+) mice by 61%, whereas forskolin (50 microM) increased alveolar fluid clearance by 55% by stimulating amiloride-insensitive pathways. Neither agent altered alveolar fluid clearance in iNOS(-/-) mice. Hyperoxia upregulated iNOS expression in iNOS(+/+) mice and decreased their amiloride-sensitive component of alveolar fluid clearance but had no effect on the corresponding values in iNOS(-/-) mice. Nasal potential difference measurements were consistent with alveolar fluid clearance in that both groups of mice had similar baseline values, which were amiloride sensitive in the iNOS(+/+) but not in the iNOS(-/-) mice. These data suggest that nitric oxide produced by iNOS under basal conditions plays an important role in regulating amiloride-sensitive Na(+) channels in alveolar and airway epithelia.     

The effects of arginine vasopressin and epinephrine on lung liquid production in fetal goats

The effects of arginine vasopressin (AVP) and epinephrine on lung liquid secretion were investigated in 67 acute fetal goats (116 days of gestation to term) with intact umbilical cords after caesarean section. Secretion was measured by an impermeant tracer technique. AVP was infused intravenously (1.6-39.2 mU/(kg.min); 2 h) into 26 fetuses. All fetuses below 130 days of gestation, except one, showed no response. All above 133 days reduced secretion, or turned to reabsorption, except at the lowest infusion rate. The effect persisted, and usually increased postinfusion. Expansion of the lungs with saline did not change the response. The percentage reductions were linearly related to the logarithm of the infusion rate (threshold, 1.42 mU/(kg.min]. The absolute reductions were linearly related to fetal weight. Epinephrine was infused intravenously (0.30-6.72 micrograms/(kg.min); 1-2 h) into 12 fetuses. All fetuses (118 days to term) reduced secretion or reabsorbed by the second hour. At the highest infusion rate, reabsorption was immediate; at the lowest, secretion increased slightly, then fell significantly in the second hour. Epinephrine acted at levels considered physiological at delivery in the sheep. AVP appears to act at plasma levels found in most vaginal deliveries; it may augment epinephrine-induced reabsorption during stress, and help long-term removal of lung fluid.     

Effects of exogenous steroids on androgen receptors in fetal guinea pig brain

We treated pregnant guinea pigs on Day 50 of gestation with 10 mg testosterone propionate (TP), obtaining fetuses 2, 4, 8, or 18 h later as well as after 5 days of treatment. In a second group of pregnant guinea pigs, dihydrotestosterone propionate (DHTP), estradiol benzoate (E2B), progesterone (P), or cortisol was given 2 h before obtaining fetuses. Although TP treatment elevated fetal serum T (p less than 0.05), brain cytosolic androgen receptor (ARc) content was unchanged in fetuses of either sex. In female fetuses, nuclear androgen receptors (ARn) increased 10-fold in medial-basal hypothalamus (MBH) and preoptic area (POA) at 2 and 4 h (respectively) after treatment, while fetal male ARn content was unchanged. Maternal injection of other steroids (E2B, P, or cortisol, but not DHTP) significantly increased these hormones in the fetus 2 h later (p less than 0.05). Only androgens affected fetal androgen receptor (AR) content. While TP increased ARn in female MBH, DHTP decreased ARc in fetal anterior pituitary of both sexes. In this latter case, a metabolite of DHT may mediate the effects. We conclude that T crosses the guinea pig placenta and activates ARn in POA and MBH of female fetuses; male ARn appear to be maximally occupied by endogenous T. Steroids of other classes do not induce AR responses in fetal guinea pig brain. These AR changes may represent an initial cellular mechanism in brain sexual differentiation.     

Cholinergic reactivity of cerebral arteries in the developing fetal and newborn lamb.

Cerebral arteries of newborn pigs and baboons constrict to acetylcholine, suggesting that endothelium-dependent dilator mechanisms may be lacking in immature cerebral arteries. The present study tested this possibility in the immature sheep by examining the response of cerebral arterioles in fetal and newborn sheep to endothelium-dependent dilator, acetylcholine. Pial arteriolar diameter was measured in 9 anaesthetized foetuses in utero (4 preterm, 90-111 days gestation and 5 term, 128-143 days gestation) and in 5 anaesthetized, newborn lambs (14 days) using a closed cranial window with intravital microscopy. Application of acetylcholine to the pial surface induced dose-dependent increase in pial arteriolar diameter in all age groups; EC50 for acetylcholine was 0.10 +/- 0.03, 0.28 +/- 0.08 and 0.26 +/- 0.17 microM for preterm fetal, term fetal, and newborn lambs, respectively. The data demonstrate a sensitive dilator response to acetylcholine in immature fetuses as well as newborn lambs suggesting that cholinergic-mediated release of endothelium-dependent relaxing factor is functional early in gestation. The contractile response to acetylcholine observed in newborn pigs and premature baboons may reflect a species difference rather than maturational lack of endothelium-dependent dilator mechanisms.     

Decline in lung liquid volume and secretion rate during oligohydramnios in fetal sheep

Reduced amniotic fluid volume often results in fetal lung hypoplasia. Our aim was to examine the effects of prolonged drainage of amniotic and allantoic fluids on lung liquid volume (Vl), secretion rate (Vs), and tracheal flow rate (Vtr) in fetal sheep. In five experimental animals, amniotic and allantoic fluids were drained from 107 to 135 days of gestation. The volume of fluid drained from the experimental animals was 411.8 +/- 24.4 ml/day (n = 140). In six control animals, amniotic fluid volume was 747.7 +/- 89.7 ml (n = 15). Wet and dry lung weights were 20-25% lower in experimental fetuses than in control fetuses. Fetal hemoglobin, O2 saturation, arterial PO2, pH, and hematocrit were unchanged by drainage. During the drainage period, Vl was up to 65% lower, Vs was up to 35% lower, and Vtr was up to 40% lower in experimental fetuses than in control fetuses. We conclude that prolonged drainage of amniotic and allantoic fluids decreases Vl, Vs, and Vtr in fetal sheep. These findings indicate that fetal lung hypoplasia associated with oligohydramnios may be the result of a prolonged reduction in Vl.     

无菌豚鼠与普通豚鼠血液学参数的比较

目的对普通级豚鼠进行剖宫产,培育无菌豚鼠模型,并比较无菌豚鼠和普通级豚鼠的血液学参数。方法行子宫摘除术摘除子宫,在无菌隔离器中将子宫剥离取仔,用人工哺乳的方法将仔豚鼠培育成无菌豚鼠,并在固定的周期检测豚鼠的无菌情况。采用全血细胞计数分析仪、全自动血液生化分析仪测定无菌豚鼠、普通豚鼠的血常规和血生化参数。用SPSS12.0进行统计分析。结果无菌豚鼠和普通豚鼠在白细胞(WBC)、嗜碱性粒细胞数(BA#)、单核细胞百分比(MO)、血红蛋白浓度(MCHC)、中性粒细胞数(NE#)、嗜酸性粒细胞数(EO#)、淋巴细胞数(LY#)七个血常规指标上有差异显著性,其他指标没有显著性差异;谷丙转氨酶(ALT)、乳酸脱氢酶(LDH)、总蛋白(TP)、白蛋白(ALB)、葡萄糖(GLU)、总胆固醇(CHO)、总胆红素(TBIL)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)、球蛋白(GLO)、A/G、K、Na、谷酰转肽酶(GGT)15个指标上差异有显著性,其他指标差异无显著性。结论通过规范的子宫摘除术和人工喂养的方法获得符合标准的无菌豚鼠,与普通豚鼠在多项血液学指标上差异有显著性。     

Effects of fetal ovine adrenalectomy on sympathetic and baroreflex responses at birth

Studies were performed to test the hypothesis that the absence of adrenal glucocorticoids late in gestation alters sympathetic and baroreflex responses before and immediately after birth. Fetal sheep at 130-131 days gestation (term 145 days) were subjected to bilateral adrenalectomy before the normal prepartum increase in plasma cortisol levels. One group of fetuses (n = 5) received physiological cortisol replacement with a continuous infusion of hydrocortisone (2 mg x day(-1) x kg(-1) for 10 days), whereas the other group received 0.9% NaCl vehicle (n = 5). All animals underwent a second surgery 48 h before the study for placement of a renal nerve recording electrode. Heart rate (HR), mean arterial blood pressure (MABP), renal sympathetic nerve activity (RSNA), and baroreflex control of HR and RSNA were studied before and after cesarean section delivery. At the time of study (140-141 days gestation), fetal plasma cortisol concentration was undetectable in adrenalectomized (ADX) fetuses and 58 +/- 9 ng/ml in animals receiving cortisol replacement (ADX + F). Fetal and newborn MABP was significantly greater in ADX + F relative to ADX animals. One hour after delivery, MABP increased 13 +/- 3 mmHg and RSNA increased 91 +/- 12% above fetal values in ADX + F (both P < 0.05) but remained unchanged in ADX lambs. The midpoint pressures of the fetal HR and RSNA baroreflex function curves were significantly greater in ADX + F (54 +/- 3 and 56 +/- 3 mmHg for HR and RSNA curves, respectively) than ADX fetuses (45 +/- 2 and 46 +/- 3 mmHg). After delivery, the baroreflex curves reset toward higher pressure in ADX + F but not ADX lambs. These results suggest that adrenal glucocorticoids contribute to cardiovascular regulation in the late-gestation fetus and newborn by modulating arterial baroreflex function and sympathetic activity.     

Alveolar epithelial fluid transport and the resolution of clinically severe hydrostatic pulmonary edema.

To characterize the rate and regulation of alveolar fluid clearance in the uninjured human lung, pulmonary edema fluid and plasma were sampled within the first 4 h after tracheal intubation in 65 mechanically ventilated patients with severe hydrostatic pulmonary edema. Alveolar fluid clearance was calculated from the change in pulmonary edema fluid protein concentration over time. Overall, 75% of patients had intact alveolar fluid clearance (>/=3%/h). Maximal alveolar fluid clearance (>/=14%/h) was present in 38% of patients, with a mean rate of 25 +/- 12%/h. Hemodynamic factors (including pulmonary arterial wedge pressure and left ventricular ejection fraction) and plasma epinephrine levels did not correlate with impaired or intact alveolar fluid clearance. Impaired alveolar fluid clearance was associated with a lower arterial pH and a higher Simplified Acute Physiology Score II. These factors may be markers of systemic hypoperfusion, which has been reported to impair alveolar fluid clearance by oxidant-mediated mechanisms. Finally, intact alveolar fluid clearance was associated with a greater improvement in oxygenation at 24 h along with a trend toward shorter duration of mechanical ventilation and an 18% lower hospital mortality. In summary, alveolar fluid clearance in humans may be rapid in the absence of alveolar epithelial injury. Catecholamine-independent factors are important in the regulation of alveolar fluid clearance in patients with severe hydrostatic pulmonary edema.