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11. |
In UteroVentilation Augments the Left Ventricular Response to Isoproterenol and Volume Loading in Fetal Sheep |
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Pediatric Research,
Volume 29,
Issue 5,
1991,
Page 466-472
DAVID TEITEL,
MICHIEL DALINGHAUS,
STEVEN CASSIDY,
BRUCE PAYNE,
ABRAHAM RUDOLPH,
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摘要:
In its normal circulatory environment, the fetal left ventricle can maximally increase output less than 2-fold, in contrast to the nearly 3-fold increase that occurs at birth. Several studies have attributed this finding to fetal myocardial “immaturity,‘’ and speculated that there is a rapid maturation of the myocardium in the perinatal period. We investigated the importance of the circulatory environment itself, rather than myocardial immaturity, by measuring left ventricular output (LVO) duringin uterooxygen ventilation and isoproterenol infusion. We studied seven near-term fetal sheep ≥2 d after placement of intravascular catheters, an endotracheal tube, and an electromagnetic flow transducer around the ascending aorta. We measured hemodynamic variables in the presence and absence of all combinations of oxygen ventilation, isoproterenol infusion, and volume infusion. Baseline LVO was normal (133 ± 27 mL·kg-1min-1). Individually, oxygen ventilation (136 ± 11 mL·kg-1·min-1,p< 0.001) and isoproterenol (48 ± 11 mL·kg-1·min-1,p< 0.05) increased LVO significantly; volume infusion did not. Their cumulative effect increased LVO nearly 3-fold (to 387 ± 98 mL·kg-1·min-1), similar to levels seen in the newborn lamb. Mean left atrial pressure increased above right during oxygen ventilation (from 0.05 ± 0.54 kPa to 0.82 ± 0.39 kPa,p≤ 0.0001). We conclude that the previously observed limitation in maximal LVO in the near-term fetus is primarily caused by its circulatory environment rather than relative myocardial immaturity, and speculate that a prominent Starling response is uncovered by decreases in left ventricular after-load and right ventricular constraint.
ISSN:0031-3998
出版商:OVID
年代:1991
数据来源: OVID
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12. |
The End‐Systolic Pressure‐Volume Relationship in the Newborn LambEffects of Loading and Inotropic Interventions |
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Pediatric Research,
Volume 29,
Issue 5,
1991,
Page 473-482
DAVID TEITEL,
R. KLAUTZ,
P. STEENDUK,
E. van der VELDE,
F. van BEL,
J. BAAN,
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摘要:
Indices of global systolic performance of the newborn left ventricle exceed those of the adult, despite isolated tissue studies showing immature contractile mechanisms. To evaluate contractilityin situ, we investigated the end-systolic pressure-volume relationship (ESPVR) by the conductance technique in nine newborn lambs. After percutaneous placement of catheters, we generated ESPVR by inferior vena cava occlusion, aortic occlusion, and volume infusion in two control states, during three levels of dobutamine infusion, and after propranolol. We performed linear and nonlinear regression analyses of the end-systolic points and derived the slope (Ees) and volume at 14 kPa pressure. We found that reliable ESPVR could be obtained in almost all inferior vena cava and aortic occlusions (50 of 51 in each), but in only 18 of 27 volume infusions. Overall, linear regressions adequately defined the ESPVR (75 of 102 were not statistically different than nonlinear regressions; of those different, the mean linear R2was 0.934 ± 0.048). By multiple regression analysis, neither Eesnor volume at 14 kPa significantly changed with dobutamine, but both changed after propranolol (23% less than control and 54% greater, respectively), supporting previous studies showing a limited contractile reserve in the newborn secondary to high resting β-adrenergic tone. Neither Eesnor volume at 14 kPa was different between control states. However, Eeswas 25% less steep when generated by inferior vena cava than by aortic occlusion. We conclude that the ESPVR can be generated reliably and reproducibly in the newborn lamb and is relatively linear and sensitive to changes in contractility, but that it is also sensitive to the technique of load intervention.
ISSN:0031-3998
出版商:OVID
年代:1991
数据来源: OVID
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13. |
Vascular Lactic Acid Infusions Do Not Alter the Incidence of Fetal Breathing Movements or Their Inhibition by Acute Hypoxemia |
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Pediatric Research,
Volume 29,
Issue 5,
1991,
Page 483-486
A. HOHIMER,
JOHN BISSONNETTE,
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摘要:
Hypoxemia transiently inhibits the incidence of fetal breathing movements (FBM), but their incidence returns to normal after several hours despite maintained hypoxemia. We hypothesized that the lactic acidosis associated with prolonged systemic hypoxemia might mediate the adaptation of the hypoxemic inhibition of FBM. In sheep fetuses, the incidence of FBM was measured in a control hour and during 6 h of i.v. infusion of L-lactic acid, which raised the blood lactate concentrations to levels seen with moderate hypoxemia. FBM were observed at the same incidence as during control during each of the first 4 h (all approximately 40%). In the 5th h of lactic acid infusion, fetal hypoxemia was induced by lowering maternal inspired oxygen fraction and FBM occurred only 8 ± 1% (SEM) of that hour. In a subsequent normoxemic recovery hour, the incidence of FBM remained below control levels. In the same animals on a different day, a similar hypoxemia induced without the acid infusion caused a comparable inhibition of FBM, but the incidence of FBM returned to the control level in a subsequent recovery hour. A moderate peripheral lactic acidosis does not blunt the inhibition of FBM evoked by acute hypoxemia and is not a likely explanation for the return of FBM during prolonged hypoxemia but actually might mediate some of the inhibition.
ISSN:0031-3998
出版商:OVID
年代:1991
数据来源: OVID
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14. |
Immunohistochemical Study on Perinatal Development of Rat Superoxide Dismutases in Lungs and Kidneys |
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Pediatric Research,
Volume 29,
Issue 5,
1991,
Page 487-491
KOHTARO ASAYAMA,
HIDEMASA HAYASHIBE,
KAZUSHIGE DOBASHI,
NORIHIKO UCHIDA,
MAKIO KOBAYASHI,
AKIRA KAWAOI,
KIYOHIKO KATO,
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摘要:
It has been reported that levels of antioxidant enzymes are low in fetal rat lungs and kidneys, and that they increase rapidly during late gestation. Among the antioxidant enzymes, both copper-zinc and manganese superoxide dismutases (CuZnSOD and MnSOD) are assumed to play a key role in protection against oxidative tissue injury. To determine the nature of the rapid perinatal increase in CuZnSOD and MnSOD, immunoenzyme staining was performed in the lungs and kidneys of fetal (d 18 and 20 of gestation) and neonatal (d 22) rats. The CuZnSOD and MnSOD in the homogenates were assayed by RIA, and they were found to be higher in the neonatal organs than in the respective fetal organs. The neonatal bronchiolar epithelium was stained for both CuZnSOD and MnSOD more intensely than the fetal one. The CuZnSOD staining in the neonatal alveolar wall was more intense than that in the fetal one. There was a significant reactivity for MnSOD in the neonatal, but not in the fetal, alveolar walls. In the kidneys, the reactivities for CuZnSOD and MnSOD were confined to the undifferentiated tubules. Although the tubules were increased in numbers in the neonatal kidneys, the intensity of the staining for both CuZnSOD and MnSOD was unchanged. The histo-chemical study disclosed that CuZnSOD and MnSOD increased in the kidneys in a manner different from that in the lungs. The low concentration of both CuZnSOD and MnSOD in the fetal lung tissues may contribute to the vulnerability to oxygen toxicity. Such changes in the concentrations is specific tissues were not delineated in the kidneys.
ISSN:0031-3998
出版商:OVID
年代:1991
数据来源: OVID
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15. |
Caffeine Acetylator Phenotyping during Maturation in Infants |
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Pediatric Research,
Volume 29,
Issue 5,
1991,
Page 492-495
ANN PARIENTE-KHAYAT,
GERARD PONS,
ELISABETH REY,
MARIE-ODILE RICHARD,
PHILIPPE D'THIS,
CLAUDE MORAN,
JEAN BADOUAL,
GEORGES OLIVE,
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摘要:
Caffeine acetylator phenotype was studied during maturation in 54 8− to 447-d-old children hospitalized for minor disease (group A) and in five 3− to 630-d-old children with Pierre Robin syndrome (group B). In group A, the children received 2.5 mg/kg caffeine orally once between birth and 15 mo. Group B patients were chronically treated with caffeine (2.3 to 15.8 mg/kg/d) for prevention of apneas, and the acetylator phenotype was serially determined. Phenotyping was performed on a spot urine sample collected 2–6 h after drug administration. Caffeine metabolites [5-acetylamino-6-formylamino-3-methyl uracil (AFMU), 1-methylxanthine, 1-methyluric acid, 1,7-methyluric acid, and 1,7-methylxanthine) were measured using HPLC. Acetylator phenotype was determined on the basis of AFMU/1-methylxanthine (ratio 1) and AFMU/AFMU + 1-methyluric acid + 1-methylxanthine + 1,7-methylxanthine + 1,7-methyluric acid (ratio 2) molar ratios. In group A, all children were slow acetylators before 83 d of age (ratio 1 < 0.4; ratio 2 < 0.08), whereas older children included slow and fast acetylators. The acetylation molar ratios differed significantly between age groups and increased with age. The cumulative percentage of fast acetylators increased with age but the plateau was not yet reached at 15 mo. In three children, the phenotyping was repeated after 15 mo: the second determination was consistent with the first one. In group B, all children appeared as slow acetylators on the first phenotyping. Four of them appeared subsequently as fast acetylators; one remained a slow acetylator until 11 mo. These results suggest that maturation of caffeine acetylation occurs during at least the first 15 mo of life for fast acetylators but is not detectable in slow acetylators. Acetylator status cannot reliably be determined before at least 15 mo.
ISSN:0031-3998
出版商:OVID
年代:1991
数据来源: OVID
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16. |
Postnatal Mice Have Low Susceptibility to Paracetamol Toxicity |
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Pediatric Research,
Volume 29,
Issue 5,
1991,
Page 496-499
GREGORY ADAMSON,
JOHN PAPADIMITRIOU,
ANDREW HARMAN,
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摘要:
The hepatotoxicity of paracetamol in mice of 2, 3, 8–10, 24–26, 32–34, and 52–54 wk of age was determined by lethality data, histopathologic examination of the liver, and appearance of glutamate-pyruvate transaminase and glutamate-oxaloacetate transaminase activities in the plasma over an 8-h exposure period. At a dose of 300 mg/kg, there was evidence of hepatocytic necrosis and transaminase leakage in the 32− to 34− and 52− to 54-wk-old mice, but lethality was only recorded in the oldest age group. At 500 mg/kg, paracetamol produced 30% lethality in 3-wk-old mice and between 50 and 90% lethality in the adult age groups. There was histologic evidence of hepatocytic necrosis at all of these ages and its extent increased with age. Similarly, there were increases in plasma transaminases in each of these age groups. However, in 2-wk-old mice there was no lethality, no hepatocytic necrosis, and no increase in plasma transaminases. The lack of susceptibility of 2-wk-old mice to paracetamol toxicity was not due to immaturity of the cytochrome P-450 enzymes responsible for metabolism of paracetamol to its reactive metabolite (N-acetyl-p-benzoquinone imine). In fact, the activity of this enzyme pathway in 2-wk-old mice was greater than that in adults. The partial clearance of the glutathione-derived metabolites of paracetamol after a nontoxic (50 mg/kg) dose was 80% greater in 2-wk-old mice than in 8− to 10-wk-old mice. Therefore, despite having greater capacity to generate N-acetyl-p-benzoquinone imine, 2-wk-old mice had no hepatotoxic effects from a dose that killed at least 50% of adult mice. Factors that relate to the detoxification of N-acetyl-p-benzoquinone imine in the liver are implicated in the lesser susceptibility of postnatal mice to paracetamol toxicity.
ISSN:0031-3998
出版商:OVID
年代:1991
数据来源: OVID
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17. |
Pharmacokinetics and Pharmacodynamics of Nifedipine in Children with Bronchopulmonary Dysplasia and Pulmonary Hypertension |
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Pediatric Research,
Volume 29,
Issue 5,
1991,
Page 500-503
CARY JOHNSON,
ROBERT BEEKMAN,
DARIA KOSTYSHAK,
TRACI NGUYEN,
DOO-MAN OH,
GORDON AMIDON,
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摘要:
The pharmacokinetics and associated pharmacodynamics of nifedipine were studied in nine children aged 5 to 68 mo with bronchopulmonary dysplasia and pulmonary artery hypertension after a single oral dose of 1.44 μmol/kg (0.5 mg/kg). In the cardiac catheterization laboratory, hemodynamic measurements were made in duplicate just before the nifedipine dose and at 5 min and 0.5 and 1.0 h after the dose. The plasma nifedipine concentration was measured by HPLC at each of the above times and at 2.5, 4.0, 6.0, and 8.0 h after the dose. The mean (± SD) maximum plasma concentration and the time to maximum plasma concentration were 243.4 ± 194.5 nmol/L and 1.0 ± 0.8 h, respectively. The mean area under the plasma concentration-time curve was 761 ± 509 nmol·h/L. The mean elimination rate constant and t1/2were 0.456 ± 0.194 h-1and 1.8 ± 0.8 h, respectively. Nifedipine caused a significant (p≤ 0.05) reduction in the mean pulmonary artery pressure by 5 min and in the mean pulmonary vascular resistance index and mean aortic pressure by 30 min, and these reductions remained significant through the 1-h measurement interval. The magnitude of acute hemodynamic response correlated closely with the plasma nifedipine concentrations. No significant change occurred in the mean arterial oxygen saturation or cardiac index during the study period. The percentage changes from baseline in the mean pulmonary artery pressure and mean pulmonary vascular resistance index were approximately double the percentage change in the mean aortic pressure, suggesting that nifedipine had some degree of selective impact on the pulmonary vascular bed. Based on these results, an initial oral maintenance regimen of 1.44 μmol/kg (0.5 mg/kg) every 6 h would be needed for this patient population. If the safety‘ and efficacy after chronic therapy can also be shown, nifedipine may prove to be an important therapeutic addition to the management of children with bronchopulmonary dysplasia and pulmonary hypertension.
ISSN:0031-3998
出版商:OVID
年代:1991
数据来源: OVID
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18. |
Modulation of Neonatal Myelopoiesis in Newborn Rats after 7 Days' Administration of Either Granulocyte‐Monocyte Colony Stimulating Factor or Interleukin‐3 |
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Pediatric Research,
Volume 29,
Issue 5,
1991,
Page 504-509
MITCHELL CAIRO,
DEBBIE MAUSS,
J. PLUNKETT,
STEVEN GILLIS,
CARMELLA DE VEN,
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摘要:
Single-pulse administration of either recombinant human granulocyte-monocyte colony stimulating factor or recombinant human granulocyte colony stimulating factor to newborn rats has previously been demonstrated to increase the peripheral neutrophil count and modulate bone marrow (BM) neutrophil pools. In our present study, we investigated the effects of 7 d of either recombinant murine granulocyte-monocyte colony stimulating factor (rmGM-CSF) (75 μg/kg/d) or recombinant murine IL-3 (rm IL-3) (10 μg/kg/d) on newborn rat myelopoiesis. Sprague Dawley newborn rats (≥24 h) were injected (intraperitoneally) daily for 7 d with either rmGM-CSF, rmIL-3, or PBS/BSA. rmGM-CSF induced a significant increase in the peripheral neutrophil count on d 3 (p< 0.03) and d 7 (p< 0.001) (75% increase). Additionally, rmGM-CSF induced a 50% increase in the BM neutrophil storage pool (p< 0.025). rmIL-3 increased the BM colony forming unit-granulocyte monocyte pool (p< 0.001); however, it failed to increase the peripheral neutrophil count or BM neutrophil storage pool. Neither CSF increased the BM neutrophil proliferate pool or BM colony forming unit-granulocyte monocyte proliferate rate. Additionally, 7 d of rmGM-CSF with or without antibiotics did not synergistically alter the mortality rate after group B streptococcol inoculation. This study suggests that rmIL-3 appears to stimulate more neonatal myeloid committed progenitor cell activity compared with rmGM-CSF. Optimal modulation of neonatal myelopoiesis may require the use of a sequential combination of hematopoietic CSF, namely an early-acting CSF followed by a more lineage myeloid-specific CSF.
ISSN:0031-3998
出版商:OVID
年代:1991
数据来源: OVID
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19. |
Ontogeny of Growth Hormone Releasing Hormone and Insulin‐Like Growth Factors‐I and‐II Messenger RNA in Rat Placenta |
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Pediatric Research,
Volume 29,
Issue 5,
1991,
Page 510-516
ORA PESCOVITZ,
NANCY JOHNSON,
SUSAN BERRY,
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摘要:
Hypothalamic growth hormone releasing hormone (GHRH) stimulates pituitary growth hormone secretion, which is essential for normal postnatal growth. Reports of an immunoreactive and biologically active GHRH-like peptide in placenta led us to investigate placenta) expression of GHRH mRNA. Placentas from d 19 gestation fetal rats were assayed for GHRH-like peptide by ELISA and for GHRH mRNA. Placenta GHRH-like peptide levels averaged 3.7 ± 0.2 ng/g tissue. Dot-blot hybridization revealed the presence of GHRH mRNA in rat placenta in quantities greater than those of the message in rat hypothalamus. Northern gel analysis of poly-A enriched RNA was used to evaluate the specificity of GHRH mRNA hybridization and to determine the size of the placental mRNA. Placental and hypothalamic GHRH mRNA were of nearly identical size, although placental RNA had a broad band of hybridization that extended below that seen in hypothalamus. Further confirmation of homology between placental and hypothalamic GHRH mRNA was determined by an RNAse protection assay, in which a placental protected fragment was identical in size to that resulting from protection of the hypothalamic complementary RNA. The ontogeny of GHRH mRNA in rat placenta was determined by dot-blot hybridization. The message was detected at the earliest date examined, d 7, and increased more than 2-fold by d 14 and 5-fold by d 17. The ontogeny of IGF-I and IGF-II mRNA in placenta was also determined. IGF-1 mRNA was detected at all gestational dates examined, but was highest on d 10, whereas IGF-II mRNA was not detectable on d 7 or 10 but was present on d 14, 17, and 20. We conclude that GHRH mRNA is present in rat placenta at least from d 7 of gestation. Placental expression of GHRH mRNA is concurrent with maximal expression of placental IGF-II, but not IGF-I mRNA. The similar time course of expression for GHRH mRNA and IGF-II leads us to speculate that they may have related functions in the last week of rat gestation.
ISSN:0031-3998
出版商:OVID
年代:1991
数据来源: OVID
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20. |
Local Cerebral Blood Flow in the Newborn RabbitAn Autoradiographic Study of Changes during Development |
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Pediatric Research,
Volume 29,
Issue 5,
1991,
Page 517-517
U. TUOR,
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摘要:
Cerebral ischemia in the neonate is an important cause of hypoxic-ischemic encephalopathy. Thus, it is important to have an economical and readily available animal model in which to study the local control of the cerebral circulation in the perinatal period. This study demonstrates that the newborn rabbit, a rather immature species at birth, is a suitable neonatal model in which to measure local cerebral blood flow with quantitative iodo[14C]antipyrine autoradiography. One or 2 d after birth, local cerebral blood flow in the newborn rabbit is low, but flow varies distinctly between regions [e.g.8.9 ± 1.5 mL kg-1·s-1(53 mL·100 g-1·min-1) in the nucleus tractus solitarius and 3.4 ± 0.7 mL·kg-1·s-1(20 mL·100 g-1·min-1) in the frontal cortex]. During early postnatal development (i.ebetween 1 and 8 d), local cerebral blood flow does not change greatly. However, by 17 d, 22 of 26 brain regions exhibit significant marked increases (200–350%) in local cerebral blood flow when compared with blood flow in the newborn. Between 17 and 40 d postnatally, cerebral blood flow continues to increase in 16 of 26 regions (e.g.thalamic areas). In four of the cerebral cortical areas, elevations in flow continue during the period between 40 d of age and adulthood. In contrast to the generalized increases in flow occurring postnatally, a few brain regions (i.e.within the pons and medulla) exhibit only minor changes in cerebral blood flow. The differential pattern and lower basal levels of cerebral blood flow in the neonate compared with the adult may be important determinants in regional susceptibility of the brain to ischemia.
ISSN:0031-3998
出版商:OVID
年代:1991
数据来源: OVID
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