摘要:

Cystic fibrosis (CF) causes early death for most homozygotes, yet has a carrier frequency among Caucasians of about 4–5%, suggesting a heterozygote advantage. The major defect in the CF gene is a three-base deletion leading to loss of a phenylalanine residue at position 508 (ΔF508) that accounts for about 68% of CF alleles in the North American population; the remaining 32% appears to consist of a large assortment of mutations. Sweat secretion in response to β-adrenergic stimulation is completely lacking in CF homozygotes and is reduced to 1/2 normal in heterozygotes. To determine if this secretory process is affected by different CF alleles, we used the polymerase chain reaction technique with DNA obtained from peripheral leukocytes to determine retrospectively the presence or absence of the ΔF508 allele in 20 CF heterozygotes for whom sweat responses to β-adrenergic stimulation had previously been determined. Twelve of 20 subjects (60%) were positive for the ΔF508 mutation. The variance in sweat responses was not reduced in the ΔF508 group, relative to the non-ΔF508 group, but a gender/allele interaction was noted.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We studied chloride efflux from isolated rabbit pancreatic acini in suspension, by loading with36Cl to steady state and rapidly washing acini by filtration to determine36Cl cpm/μg DNA remaining. Linear loss of acinar chloride occurred over 5 min (k = 0.038 ± 0.008 min-1,n= 5). Forskolin (5 x 10-5M) increased the rate of chloride efflux (k = 0.100 ± 0.016 min-1,n= 5,p< 0.001) 2.6-fold. At 5 min, forskolin increased acinar cAMP levels (1065 ± 254versus7 ± 2 pmol/mL,n= 5,p< 0.005) and percentage of chloride efflux (37.4 ± 2.3versus26.0 ± 2.2%,n= 13,p< 0.005). The chloride channel inhibitor anthracene-9-carboxylic acid (10-3M) had no effect on chloride loss from acini exposed to vehicle (30.9 ± 1.9versus29.9 ± 2.3%,n= 4), but completely inhibited forskolin-stimulated efflux at 5 min (40.0 ± 2.4versus29.3 ± 2.4%,n5,p, < 0.005). Manipulation of extracellular calcium concentration demonstrated that chloride efflux was not coupled to zymogen granule amylase release. Secretin (10-7M) increased acinar cAMP levels (68 ± 22versus7± 2 pmol/mL,n= 5,p< 0.05) and significantly increased the loss of chloride from acini (34.9 ± 1.4versus26.1 ± 1.7%,n= 7,p< 0.005) without affecting amylase release. Secretagogue-stimulated amylase release by cholecystokinin octapeptide (10-8M) and carbamylcholine (10-5M), did not increase chloride efflux at 5 min. Our findings demonstrate that pancreatic acini possess a chloride efflux pathway that is conductive, cAMP responsive, and distinct from zymogen granule membrane conductance.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Because of cocaine's possible effect on the incidence of respiratory distress syndrome in offspring of cocaine-addicted mothers, we have studied the effects of maternal exposure to cocaine on the functional anatomy of fetal rabbit lungs. Pregnant dams were injected s.c. daily with either cocaine (18 mg/kg) or an equal volume of 0.9% NaCl at 24, 25, and 26 d gestation. Cocaine metabolites were confirmed both in urine of treated dams and in fetal amniotic fluid. Serum cortisol levels were higher in treated dams than in controls. Fetuses were delivered through hysterotomy at 27 d. Tracheas were cannulated and a volume-pressure diagram was obtained during initial lung inflation-deflation. Volume was measured for 2 min at each pressure (P) increment of 5 cm H2O. Body weights and dry lung weights were comparable between the two groups. In contrast, cocaine-exposed lungs differed from controls as follows:I) wet lung weights were lower (0.79versus0.89 g,p< 0.02);2) opening pressure was lower (P25versusP35);3) volume (ml/kg) was higher in treated animals at each pressure step (p< 0.05);4) end-deflation volume at P0 was higher (30.4versus0.8 mL/kg,p< 0.001); and5) bubbles released from saccules by micropuncture, which were stable by Pattle's criteria, had estimated surface tension near zero (controls produced no stable bubbles). Light micrographs of cocaine-exposed fetuses revealed more secondary septa and thinner septal walls than controls. We conclude that fetal exposure to cocaine results in increased lung distensibility and stability, induction of low surface tension, and morphologic transformations, each of which is consistent with accelerated lung maturation. The cortisol surge suggests a steroid-mediated mechanism for this effect.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Endothelium-derived relaxing factor (EDRF), believed to be nitric oxide or a compound that releases nitric oxide, has been previously identified in the pulmonary and systemic vasculature of the new born guinea pig using isolated arterial rings. The aim of our study was to determine if EDRF regulates vasomotor tone at the level of resistance vessels in the neonatal pulmonary circulation. Isolated lungs from guinea pigs (1–3 d old,n= 4–8/protocol) were ventilated with room air and perfused with a Krebs-Henseleit solution containing albumin at a constant flow. Angiotensin II (AII, 6 nM) was added to the perfusate to give a stable elevation in mean pulmonary artery pressure (PAP) from 7.0 ± 1.1 to 19.7 ± 1.5 torr, a 182 ± 32% (mean ± SEM) increase above baseline. Addition of bradykinin (BK, 10 nM) or L-arginine (2 mM) markedly reduced the All-induced elevation in PAP. At the steady state response to BK (33% above baseline), addition of Hb (10 μM, binds EDRF), NG-monomethyl-L-arginine (NMA, 100 μM, blocks EDRF production), NMA (200 μM), or NMA + Hb, reversed the effect of BK to the following levels of PAP above baseline: 77 ± 5, 94 ± 24, 163 ± 20, or 246± 25%, respectively (p< 0.05). Indomethacin had no effect on BK-induced vasodilation. In separate studies, NMA (200 μM) increased baseline PAP by 46 ± 13% and NMA pretreatment raised the AII-pressor response (AII 6 nM) from 133 ± 49 to 306 ± 65% above baseline PAP. NMA (200 μM) pretreatment also inhibited the dilator action of submaximal doses of BK on the AII-induced elevation of PAP. We conclude that, in the isolated neonatal guinea pig lung, EDRF plays an important role in the:l) control of baseline PAP,2) vasoreactivity of AII. and3) dilator mechanism of BK, EDRF may play an important role in the pulmonary hemo-dynamick adjustments at birth.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Reactive oxygen metabolites appear to modulate pulmonary vascular changes. To study the effects of free radical formationin vivo, we investigated five groups of young pigs by recording hemodynamic changes after xanthine oxidase infusion alone and after pretreatment with hypoxanthine or possible blocking agents. The pulmonary vascular pressure increased rapidly in the groups without inhibition reaching maximum levels 25 min after the start of the experiment. The pulmonary artery blood flow declined toward minimum values at the same time. Compared to baseline levels, the calculated vascular lung resistance increased by 300% when the pigs were pretreated with hypoxanthine, and by 150% when xanthine oxidase was given alone. These findings suggest enhanced pulmonary vasoconstriction as a result of high initial hypoxanthine levels probably capable of forming larger quantities of oxygen radicals. The vascular reaction was attenuated when the pigs were pretreated with indomethacin (cyclooxygenase inhibitor) or allopurinol (xanthine oxidase inhibitor). Furthermore, the presence of catalase (hydrogen peroxide scavenger) reduced the pulmonary vasoconstriction significantly. We observed less decline in arterial oxygen tension and oxygen saturation when the animals had been pretreated with inhibitory agents, compared to the blood gas changes found in the xanthine oxidase group. The systemic pressure recordings in the carotid artery remained at baseline levels in all groups. We conclude that oxygen radicals formed by the hypoxanthine-xanthine oxidase system produce severe pulmonary vascular constriction in young pigs.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

To define respiratory effects of peripheral acidemia during early development, we injected lactic acid (LA) into the jugular vein of 32 1− to 7-d-old rabbit pups and four adult rabbits. The body weight of newborns varied between 67 ± 17 g in 1-d-old and 119.8± 33.7 g in 7-d-old animalsversus4 ± 0.1 kg in adults. Animals were anesthetized with ketamine (30 mg/kg) and urethane (0.6–1.2 g/kg), tracheotomized, and breathed spontaneously. Diaphragmatic electromyogram, tidal volume, esophageal pressure, and arterial pressure were recorded. In adult rabbits, a LA dose of 0.25 mM/kg elicited an increase in the rate of breathing with no change or a decrease in tidal volume (early response), followed by a deep and fast respiration (late response). The same LA dose had no effect or provoked only the late response in 1-and 2-d-old rabbits and led to the early and late responses in older newborns. The early response was abolished and the late response was diminished after vagotomy. Our results suggest that the early response is mediated by vagal afferents and the late response, althoughmodified by vagal input, is of an extravagal origin. It is suggested that acidemia may be involved in the transient tachypnea syndrome in new born infants. Possible contribution of vagal nonmyelinated endings in triggering the early response to LA is discussed.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The response of cerebral blood volume (CBVR) to a small induced change in arterial carbon dioxide tension was studied by near-infrared spectroscopy in 17 newborn infants born from 26 wk of gestation to term. All 17 infants were undergoing mechanical ventilation but had apparently normal brains. The CBVR per kPa change in arterial carbon dioxide tension within the range 3.9 to 9.6 kPa was calculated from the change in total cerebral Hb concentration ([TCHb]) using the equation: ΔCBV = Δ[TCHb] x 0.89/[H] where [H] is the large vessel Hb concentration. A least-squares regression line with 95% confidence limits was derived for CBVR against gestational age. A highly significant linear increase in CBVR was found: mean CBVR from the regression increased from 0.07 mL·100 g-1·kPa-1at 26 wk to 0.51 mL·100 g-1·kPa-1at 40 wk.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Glucocorticoid therapy is frequently used in perinatology and neonatology for its beneficial pulmonary effects. We investigated the influence of neonatal glucocorticoid administration on brain damage caused by a concurrent episode of cerebral hypoxia-ischemia. Various doses of dexamethasone in several treatment schedules were administered to 7-d-old rats that were also subjected to unilateral cerebral hypoxia-ischemia. In 79% of control rats, a large unilateral cerebral infarction occurred, whereas all rats pretreated with dexamethasone in doses of 0.01 to 0.5 mg/kg/d for 3 d had no infarction (p< 0.001). The neuroprotective effect of dexamethasone pretreatment was dose- and time-dependent. Treatment with dexamethasone after the insult or with lower doses before the insult did not prevent infarction. The neuroprotective effect was not immediate: single doses 0 to 3 h prehypoxia were not effective but a single dose 24 h before hypoxiaischemia prevented cerebral infarction. The results demonstrate that glucocorticoid administration in the neonatal period, even in low doses, protects the brain during subsequent periods of hypoxia-ischemia.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

To determine the relative importance of patent ductus arteriosus, indomethacin, and intestinal distension as factors that promote terminal ileum ischemia, eight near-term fetal lambs were surgically prepared byin situcannulation of the proximal and distal ends of a loop of terminal ileum, formalin infiltration of the ductus arteriosus, and placement of a snare around the ductus arteriosus to control its patency. The incisions were closed; the lambs were delivered and mechanically ventilated. Terminal ileum blood flow and oxygen consumption were measured after the loop of ileum had been distended with 0.9% NaCl to luminal pressures of 1–2, 7, and 18 mm Hg (0.13–0.26, 0.93, and 2.38 kPa) (pressures observed in the intestinal lumen after feeding and during pathologic conditions). The effect of these pressures on terminal ileum blood flow and oxygen consumption was examined:I) with ductus closed,2) with ductus open, and3) 1 h after administration of indomethacin (0.3 mg/kg; 0.8 μmol/kg) with ductus closed. Both open ductus and indomethacin produced a significant decrease in intestinal blood flow. This occurred over the entire range of luminal pressures examined. In all three study conditions, terminal ileum blood flow fell commensurate with a fall in perfusion pressure. Despite this absence of pressure-flow autoregulation, oxygen consumption was maintained when the ductus was closed or open. In contrast, indomethacin inhibited the ability of the terminal ileum to autoregulate its oxygen consumption. These findings suggest that both open ductus and indomethacin present an increased risk of intestinal ischemia. We hypothesize that indomethacin's beneficial effect on ductus closure may be counterbalanced by its negative effect on intestinal perfusion and metabolism.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Previous studies demonstrated that the time required for oxygen uptake, CO2production, and minute ventilation to return to baseline levels after 1-min bursts of exercise is different in children compared with adults. To test the hypothesis that the heart rate (HR) recovery time after exercise is also different in children compared with adults, we examined HR in 10 children (range 7–11 y old) and 12 adults (26–42 y old) for 10 min after 1 min of cycle ergometer exercise. Each subject exercised at work rates corresponding to 80% of the lactate or anaerobic threshold (AT), 50% of the difference between AT and maximal O2uptake (Δ), 100% of maximal uptake, and 125% of maximal uptake. Gas exchange was measured breath by breath. In adults, the HR recovery time increased significantly with work intensity as judged by the time constant of a single exponential curve fit to postburst-exercise HR [23 ± 8 (SD) s at 80% AT, 55 ± 16 at 50%Δ, 74 ± 13 at 100% of maximal uptake, and 83 ± 20 at 125% of maximal uptake]. HR recovery time tended to increase with work intensity in children (16 ± 7, 20 ± 4, 23 ± 7, and 27 ± 9; for 80%AT, 50%Δ, 100% of maximal uptake, and 125% of maximal uptake respectively), but to a much smaller extent, and the HR recovery time was significantly smaller in children in the high-intensity (above AT) range of exercise (p < 0.001). Despite the markedly faster recoveries in children, the time course of the O2, pulse (Vo2/HR) was indistinguishable between children and adults. These data suggest that the regulation of HR after high-intensity exercise is different in children compared with adults, and that the pulsatile delivery of O2to the tissues is controlled during the growth period.

ISSN:0031-3998    

出版商:OVID    

年代:1991

数据来源: OVID