Biology of the neonate最新文献

Beta-adrenergic receptor (betaAR) activation has been shown to maintain heart rate during hypoxia and to rescue the fetus from the fetal lethality that occurs in the absence of norepinephrine. This study examines whether the same subtype of betaAR is responsible for survival and heart rate regulation. It also investigates which betaARs are located on the early fetal heart and whether they can be directly activated during hypoxia. Cultured E12.5 mouse fetuses were treated with subtype-specific betaAR antagonists to pharmacologically block betaARs during a hypoxic insult. Hypoxia alone reduced heart rate by 35-40% compared to prehypoxic levels. During hypoxia, heart rate was further reduced by 31% in the presence of a beta(1)AR antagonist, CGP20712A, at 100 nM, but not with a beta2 (ICI118551)- or a beta3 (SR59230A)-specific antagonist at 100 nM. Survival in utero was also mediated by beta1ARs. A beta1 partial agonist, xamoterol, rescued 74% of catecholamine-deficient (tyrosine-hydroxylase-null) pups to birth, a survival rate equivalent to that with a nonspecific betaAR agonist, isoproterenol (87%). Receptor autoradiography showed that beta1ARs were only found on the mouse heart at E12.5, while beta2ARs were localized to the liver and vasculature. To determine if the response to hypoxia was intrinsic to the heart, isolated fetal hearts were incubated under hypoxic conditions in the presence of a betaAR agonist. Heart rate was reduced to 25-30% by hypoxia alone, but was restored to 63% of prehypoxic levels with 100 nM isoproterenol. Restoration was completely prevented if beta1ARs were blocked with CGP20712A at 300 nM, a concentration that blocks beta1ARs, but not beta2- or beta3ARs. Our results demonstrate that beta1ARs are located on the heart of early fetal mice and that beta1AR stimulation maintains fetal heart rate during hypoxia and mediates survival in vivo.

Current standard therapy for persistent pulmonary hypertension of the newborn (PPHN) consists of optimal lung inflation, hemodynamic support and selective vasodilation with inhaled nitric oxide (iNO). However, not all infants will respond. Milrinone, a phosphodiesterase (PDE) III inhibitor, is routinely used in pediatric cardiac intensive care units to improve inotropy and reduce afterload. Although its use in post-operative cardiac failure has been proven in a randomized trial, it has not been reported to be beneficial in PPHN. We report four cases with severe PPHN treated with a combination of iNO and Milrinone. All four cases were unresponsive to therapy including iNO, with a mean oxygenation index (OI) of 40 (standard deviation (SD) 12)) before Milrinone. Substantial improvement in OI (mean of 28; SD 16) was followed by extubation and survival. However, of 4 patients, 2 developed serious intraventricular hemorrhages (IVHs), and 1 had a small IVH. To clarify the risk benefit ratio, of death versus survival with impairment, a randomized controlled trial is needed.

Abnormalities of limbs are important features of some syndromes recognizable at birth. The purpose of this study was to establish normal standards of limbs including arm length, arm circumference, upper arm length, lower arm length, leg length, thigh circumference, upper leg length, and lower leg length. 10,226 infants (5,422 males, 4,804 females) with gestation 28-42 weeks from 12 hospitals were included. The LMS method using maximum penalized likelihood was used to perform model fitting of the anthropometric centiles for these parameters. This study provided the first set of references for the limbs of the infants by gestation and gender. Racial differences were found when comparing with other populations. The parameters are useful for evaluation of morphologic disorders involving the limbs.

Background: Administration of hydrocortisone and relatively high doses of dexamethasone increase blood pressure in volume- and pressor-resistant hypotensive preterm infants. However, little is known about the temporal relationship of dexamethasone administration and the improvement in blood pressure and the weaning of pressors/inotropes. Furthermore, there are no sufficient data available on whether a smaller dose of dexamethasone would also be effective in treating refractory hypotension.

Objective: To study the cardiovascular responses to low-dose dexamethasone in very low birth weight neonates with volume- and pressor-resistant hypotension.

Methods: Retrospective database review. Twenty-four preterm neonates (gestational age 26 (23-34) weeks; birth weight 801 (457-1,180) g; postnatal age 2 (1-24) days, medians (ranges)) who remained hypotensive despite volume administration and combined dopamine and dobutamine treatment at >or=30 microg/kg/min received dexamethasone 0.1 mg/kg followed by 0.05 mg/kg intravenously every 12 h for 5 additional doses if still on pressors >or=8 microg/kg/min.

Results: Two hours after the first dose of dexamethasone the mean blood pressure increased from 30 +/- 5 to 34 +/- 6 mm Hg (p < 0.001) and remained elevated at 4, 6, 12, and 24 h after treatment was started (p < 0.001). Six hours after the initial dose of dexamethasone the pressor/inotrope requirement decreased from 34 +/- 9 to 24 +/- 13 microg/kg/min (p = 0.001) and continued to decrease at 12 and 24 h (p < 0.001). Urine output also increased significantly during the first 6 h after dexamethasone (p < 0.001).

Conclusions: Low-dose dexamethasone rapidly increases blood pressure and decreases pressor requirements in very low birth weight neonates with volume- and pressor-resistant hypotension.

Background: Cardiac troponins T (cTnT) and I (cTnI) are well-established markers in detecting myocardial ischemic damage in adults. Perinatal asphyxia is associated with cardiac dysfunction.

Objectives: To evaluate serum concentrations of cTnI in asphyxiated neonates and to investigate whether cTnI is correlated with the traditional markers of asphyxia.

Methods: Blood samples were collected from 13 asphyxiated neonates (umbilical artery pH<7.18 and either a 1-min Apgar score<4 or a 5-min Apgar score<7) and 39 controls. Data on gestation, birth weight, sex, Apgar scores, mode of delivery, umbilical pH, creatinine, serum activity of aspartate and alanine aminotransferase, and QTc interval were investigated.

Results: Median (range) cTnI concentrations were significantly higher in asphyxiated neonates with respect to healthy infants: 0.36 microg/l (0.05-11) versus 0.04 microg/l (0.04-0.06); p<0.01. In asphyxiated babies, no statistically significant correlations were found between concentrations of cTnI and the other markers of asphyxia.

Conclusions: In asphyxiated neonates, cTnI concentrations are higher with respect to healthy infants, suggesting the presence of myocardial damage in this group of high-risk patients. cTnI does not correlate with the traditional markers of asphyxia.

Background: Dysfunctional inflammatory responses have been implicated in several neonatal inflammatory disorders following infection and hypoxia.

Objectives: We aimed to study the effects of in vitro hypoxia and heat shock (HS) on normal adult and newborn neutrophil migration (CD11b) and persistence (apoptosis) following lipopolysaccharide (LPS) stimulation.

Methods: The mechanism for altered LPS responses was assessed at the level of the LPS signalling receptors, Toll-like receptor-4 (TLR-4), TLR-2 and CD14 expression in normal neonates and adults.

Results: In adults, although hypoxia delayed neutrophil apoptosis, LPS enhanced this response. In contrast, HS (42 degrees C) increased adult apoptotic rates and abrogated the LPS responses. Both hypoxia and HS prevented the LPS-induced increase in adult CD11b although it was unaltered in neonates. Adult TLR-4 neutrophil expression was increased by LPS and hypoxia, and decreased in HS, possibly explaining their variable LPS responsiveness. In contrast, neonatal neutrophils were LPS hyporesponsive which may be mediated by failure of TLR-4 upregulation with LPS.

Conclusions: Neonates do not have increased LPS responsiveness in hypoxia or heat shock in vitro, which may prevent hyperinflammation and thereby minimise tissue damage in inflammation or infection.

Preterm infants exposed to mechanical ventilation often develop airway dysfunction and bronchopulmonary dysplasia. The mechanisms of mechanical ventilation-induced airway injury are currently unknown. This study correlates the age-related effects of mechanical ventilation on airway function with structural alterations at the tissue, cellular, ultrastructural, and molecular levels. Mechanically ventilated and nonventilated tracheal rings were obtained from premature and newborn lambs. In tissue baths, the passive and active length-tension relationships and dose-response characteristics of the tracheal rings were determined. Fixed tracheal rings were digested and the resulting isolated smooth muscle cells measured. Rings were analyzed by light and electron microscopy. Additionally, protein was extracted from the tracheal smooth muscle and myosin heavy chain isoforms were separated by SDS-polyacrylamide gel electrophoresis and analyzed by densitometry. Mechanical ventilation resulted in a significant decrease of both the slope of the passive length-stress relationship and of maximal force generation, with both effects being most pronounced in the newborn age group. These age-related functional alterations correlated with a decrease in smooth muscle cell length and a disruption of ultrastructural architecture, which were also most pronounced in the older groups. Furthermore, mechanical ventilation resulted in epithelial denudation at all ages. There were no acute statistically significant effects of mechanical ventilation on myosin heavy chain isoform expression. This study demonstrates age-related effects of mechanical ventilation on the passive and active characteristics of tracheal function and provides a structural analysis of potential mechanisms. The mechanisms behind these functional differences involve ultrastructural changes in cell length, tissue matrix, and disruption of epithelial integrity. These findings help elucidate the pathogenesis of ventilator-induced airway injury.

Introduction: Diabetes mellitus (DM) during pregnancy is associated with an increased risk for poor reproduction and a high rate of congenital malformations. The gerbil Psammomys obesus is a unique model for nutritionally induced Type 2 DM (T2DM) that enabled us to study the outcome of uncontrolled T2DM during pregnancy.

Methods: Female Psammomys on low-energy (LE) or high energy (HE) diet were studied. The blood glucose levels and weights of pregnant animals were determined. The offspring from the different groups were followed-up to weaning.

Results: Most of the HE-diet animals were diabetic (77%). There were no differences in the pregnancy rates in animals on both diets (32.7% in HE vs. 38.3% in LE). Pregnancy of the HE-diet group was longer than the LE-diet group (26.7 vs. 26.1 days), and litter average was reduced (2.7 vs. 3.0). At birth, the offspring of the HE-diet dams weighed less (5.2 vs. 7.2 g) and had smaller crown rump length (4.0 vs. 4.6 cm) These offspring also presented a 1-3 days delay in neuro-developmental parameters (first turn over, hair appearance, eye-opening and response to noise). However, from the fourth week of life they became diabetic, and from the third week they weighed more than the LE offspring.

Conclusion: HE-diet caused diabetes, maternal complications and altered reproduction in Psammomys animals. The offspring of diabetic Psammomys presented birth weight and length changes as well as developmental delay.

The purpose of this review article is to document from the literature values of blood/plasma glucose concentration and associated clinical signs and conditions in newborn infants (both term and preterm) that indicate a reasonable clinical probability that hypoglycemia is a proximate cause of acute and/or sustained neurological injury and to review the physiological and pathophysiological responses to hypoglycemia that may influence the ultimate outcome of newborns with low blood glucose. Our overall conclusion is that there is inadequate information in the literature to define any one value of glucose below which irreparable hypoglycemic injury to the central nervous system occurs, at any one time or for any defined period of time, in a population of infants or in any given infant. Clinical signs of prolonged and severe neurological disturbance (coma, seizures), extremely and persistently low plasma/blood glucose concentrations (0 to <1.0 mmol/l [0 to <18-20 mg/dl] for more than 1-2 h), and the absence of other obvious central nervous system (CNS) pathology (hypoxia-ischemia, intracranial hemorrhage, infection, etc.) are important for the diagnosis of injury due to glucose deficiency. Specific conditions, such as persistent hyperinsulinemia with severe hypoglycemic episodes that include seizures, also contribute to the diagnosis of hypoglycemic injury. Such lack of definitive measures of injury specific to glucose deficiency indicates that clinicians should be on the alert for infants at risk of hypoglycemia and for clinical signs and conditions that might herald severe hypoglycemia; they should have a low threshold for investigating and diagnosing 'hypoglycemia' with frequent measurements of plasma/blood glucose concentration; and they should treat low glucose concentrations promptly and maintain them in a safe range. Because there is no conclusive evidence or consensus in the literature that defines an absolute value or duration of 'hypoglycemia' that must occur, with our without related clinical complications, to produce neurological injury, clinicians should consider the information currently available, determine a 'target' plasma or blood glucose concentration that is acceptable, and treat infants with glucose concentrations below this value accordingly. Our intent in this review article is to highlight the studies relevant to this issue and help clinicians formulate a safe and, hopefully, effective strategy for the diagnosis and treatment of hypoglycemia.

Background: Among newborns who die, those who have cerebral white matter damage are more likely than others to have thymus involution and low thymus weights.

Objective: We sought to evaluate in a population of preterm newborns who did not die if those who developed a cerebral white matter damage (as defined by an echolucency) are more likely than others to have thymus involution as assessed on chest radiographs.

Method: The 89 infants whose data were evaluated were born before the 28th week of gestation, had at least one chest radiograph within the first 2 days of life (to determine thymus size), and at least one cranial ultrasonogram to assess for white matter echolucency.

Results: Eighty-five percent of these infants had a small thymus within the first 2 weeks of life. Median time to thymus involution in those born before the 26th week of gestation was 36 h, and in those born during or after the 26th week of gestation was 140 h. Infants who developed involution before the median time in their respective gestational age groups were classified as early involuters (group 1) and were compared to their peers with late/no involution (group 2). Infants with an echolucency were more likely to have had early involution than infants without an echolucency (89% vs. 44%) (p = 0.01). This relationship was not distorted by potential confounders. The echolucency odds ratio associated with early thymus involution was consistently above 8 in all strata of the sample.

Conclusion: These results are consistent with the possibility that early thymus involution and neonatal white matter damage are not independent phenomena and may have common antecedents.