ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Ca2+transients were examined in embryonic chick hearts with an experimentally induced cardiac neural crest-related outflow tract defect known as persistent truncus arteriosus (PTA). In all of the animal models of neural crest-related heart defects, prenatal mortality is too high to be attributed to structural defects of the heart alone, suggesting that there is altered development of the myocardium. Earlier reports indicating reduced L-type Ca2+current in hearts with PTA suggest that poor viability may be related to impairment of cardiac excitation-contraction coupling. To test this hypothesis, direct measurements of the systolic Ca2+transient in fura-2-loaded myocytes from normal hearts and hearts with PTA were carried out. We found that Ca2-transients were severely depressed in hearts with PTA and difficult to measure above background noise unless signal averaged or treated with isoproterenol (ISO). We confirmed that the reduced Ca2+transients were due, at least partly, to a reduction in L-type Ca2+current. In addition we found that although ISO could raise the L-type current in hearts with PTA to the level found in normal hearts in the absence of ISO, it could not fully restore the Ca2+transient. Furthermore, caffeine-stimulated Ca2+transients were diminished in size and the time-to-peak and the decaying phase were significantly slowed. Interestingly, these observations were not accompanied by a reduction in the number of Ca2+release channels. These results indicated an impairment of SR function in addition to the reduction in L-type Ca2+current. These results strongly support our hypothesis that the poor viability of embryos with PTA is due to impaired cardiac excitation-contraction coupling.

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Effective attenuation of pulmonary vasoconstriction is essential during early postnatal development when increased pulmonary vascular resistance (PVR) may lead to a resumption of right-to-left shunting across fetal channels. In addition, modulation of venous resistance contributes to normal lung fluid balance. This study was designed to identify the relative modulating effects of endothelium-derived nitric oxide (EDNO) and dilator prostaglandins (PG) on normoxic and hypoxic pulmonary vasomotor tone in young newborns. Total and segmental PVR were measured using inflow-outflow and double occlusion techniques in isolated lungs of 6-h-old lambs studied under control conditions or after blocking PG and/or EDNO synthesis with indomethacin and/orNω-nitro-L-arginine, respectively. During normoxia, both indomethacin andNω-nitro-L-arginine were required to increase total PVR, but EDNO appeared to have the greater modulating effect. Indomethacin markedly enhanced hypoxic pulmonary vasoconstriction of large and small arteries and small veins, whereasNω-nitro-L-arginine caused a lesser, but significant, increase in hypoxic pulmonary vasoconstriction of small arteries and veins, suggesting that dilator PG played the dominant modulating role during hypoxia. In addition, PG synthesis appeared to be enhanced after inhibition of EDNO synthesis. In contrast, indomethacin caused a decrease in venous resistance, suggesting that constrictor prostanoids had a greater effect than dilator PG on this segment. EDNO had a modest modulating effect on venous resistance in these lungs. These data suggest that dilator PG and EDNO exert complementary effects in attenuating total and segmental PVR during normoxia and hypoxia in 6-h-old lamb lungs.

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Chronic lung disease in neonates results from both lung injury and inadequate repair processes. Little is known about the growth factors involved in lung injury and repair, but vascular endothelial growth factor (VEGF) has recently been reported in several animal models of lung injury. VEGF is an endothelial cell-specific mitogen, which is also known as vascular permeability factor because of its ability to induce vascular leak in some tissues. Chronic lung disease is complicated by increased vascular permeability, which can be improved by avoidance of hypoxia and in some cases by dexamethasone therapy. In many cells, hypoxia stimulates VEGF expression. Also, in some cases, dexamethasone blocks VEGF expression. This study examined the role of hypoxia and dexamethasone in regulating the expression of VEGF in pulmonary artery smooth muscle cells. An ovine VEGF cDNA fragment (453 bp) was cloned and found to be highly homologous to known human sequences for VEGF165. Sheep pulmonary artery smooth muscle cells were cultured and exposed to room air, hypoxia, and dexamethasone, alone or in combination for 6 h. At baseline these cells expressed VEGF mRNA at approximately 3.9 kb. The half-life of VEGF mRNA in the smooth muscle cells was 171 min, more than 3-fold longer than previous reports for epithelial cells. Exposure to hypoxia caused a 3-fold increase in mRNA abundance, primarily through transcriptional up-regulation. Dexamethasone blocked the hypoxia-induced increase in VEGF mRNA. The results demonstrate that hypoxia and dexamethasone are regulators of VEGF expression in ovine pulmonary artery smooth muscle cells. It is not known whether VEGF derived from these cells is involved in lung injury and/or normal homeostatsis.

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The purpose of the present study was to determine developmental changes in the effect of respiratory acidosis on vascular smooth muscle contraction. Vessel diameter, intracellular pH (pHi), and calcium concentration ([Ca]i) were measured in a cannulated preparation of the small mesenteric artery of newborn and adult rabbits. In the artery precontracted by high KCl, acidosis caused a vasorelaxation both in the newborn and the adult; the vasorelaxation was greater in the newborn than in the adult. The fura-2 fluorescence ratio, an indicator of[Ca]i, decreased transiently during acidosis and the decrease was similar in the two age groups. In the artery precontracted by norepinephrine, acidosis caused a transient vasoconstriction in the adult and a vasorelaxation in the newborn. In these vessels, the fura-2 fluorescence ratio increased transiently during acidosis; the increase was similar in the two groups. Upon induction of acidosis, pHifell rapidly in the artery precontracted by norepinephrine or high KCl, and the depression of pHiwas similar in the two groups. In the skinned smooth muscle preparation, a tension-[Ca] relationship curve at pH 7.1 was not significantly different from that at pH 6.8 in the adult. In the newborn, the tension-[Ca] curve at pH 6.8 was shifted to the right, compared with that at pH 7.1. These data suggest that the vasorelaxant effect of respiratory acidosis in the premature vessel is greater than in the adult. The greater vasorelaxation in the newborn cannot be explained by the age-related difference in pHior [Ca]iduring acidosis. The greater sensitivity of myofibrils to low pHiin the newborn may, at least in part, be responsible for the greater vasorelaxation in this age group.

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Disproportionate fetal and placental growth are associated with the development of hypertension in the rat and human. Here we report differences in fetal, neonatal, and placental growth, and in metabolism and endocrinology, between the spontaneously hypertensive rat (SHR), a genetic model for human essential hypertension, and the control Wistar-Kyoto (WKY) strain. Gestation in SHR (23 d) was longer than in WKY by 20 h. Body weights were lower in the SHR from fetal d 16 to 20 and on postnatal d 15. However, on fetal d 22 and postnatal d 1, there was no significant difference in body weight between SHR and WKY. SHR placentas were larger than those of WKY at d 20, and by term there was a difference of 30% (p< 0.01). Other indices of disproportionate growth were hypertrophy of the fetal heart and kidney and decreased ponderal index in the SHR neonate. Blood glucose in SHR fetuses was lower than in WKY fetuses (p< 0.05), whereas blood lactate was higher (p< 0.05) and fetal hematocrit was reduced (p< 0.001). These findings suggest undernutrition and placental insufficiency may occur in SHR fetuses. Plasma IGF-II was increased on the last day of gestation in both strains, whereas IGF-I was unaltered. Fetal liver IGFBP-2 mRNA and plasma IGFBP-2 levels were reduced in SHR on fetal d 20 and 22(p< 0.01). Differences in growth and endocrine and metabolic parameters suggest abnormal perinatal physiology in the SHR, which may influence the later development of hypertension.

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Arterial, venous, and intracardiac Doppler flow velocity waveforms were studied in 50 women with a small for gestational age (SGA) fetus according to a cross-sectional study design. No Doppler signals could be obtained in five women for technical reasons. The remaining 45 women were compared with normal control subjects matched for gestational age and maternal parity. The 45 SGA fetuses were divided into birth weight below the 5th centile for gestational age (group I,n= 35) and birth weight between the 5th and 10th centile for gestational age (group II,n= 10). A significant difference in baseline characteristics was found between both SGA subsets and normal controls. In SGA I fetuses, the pulsatility index in the umbilical artery and descending aorta was significantly higher, but lower in the middle cerebral artery when compared with normal controls. At the atrioventricular and venous level (umbilical vein, ductus venosus, and inferior vena cava) reduced time-averaged velocities were established. PIV in the ductus venosus and IVC showed a significant increase. Within the same SGA subset, no relationship could be established between arterial downstream impedance and1) atrioventricular flow velocities and 2) pulsatility index in the ductus venosus and inferior vena cava. Also, no relationship existed between flow velocity waveforms and pregnancy-induced hypertension and admission to the neonatal intensive care unit. Umbilical venous pulsations and absent/reverse flow in the umbilical artery were associated with a high intrauterine mortality rate and low birth weights. In SGA II fetuses, the pulsatility index in the umbilical artery and decending aorta was significantly higher than in normal controls. It can be concluded that fetuses with a birth weight below the 5th centile demonstrate marked changes in arterial, atrioventricular, and venous flow velocity waveforms. Atrioventricular and venous flow velocity waveforms change independently from arterial downstream impedance, suggesting that other factors, such as reduced volume flow and myocardial contraction force, may play a role in the observed changes.

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

A factor V506Arg-Gln mutation is the most common inherited cause of thrombophilia in adults. To date, there are no data regarding the detection of this mutation in neonatal blood or the relationship of this dysfunctional factor V to neonatal thrombosis. This study compared a modified activated protein C resistance functional assay with the PCR-based DNA assay for the factor V mutation in 115 prospectively collected umbilical cord blood samples. The incidence of activated protein C resistance in cord blood was 6%. The sensitivity and specificity of the modified assay for the factor V Leiden mutation was 100%.

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Previous studies have shown that the endogenous inflammatory mediator platelet-activating factor (PAF) plays an important role in the pathophysiology of neonatal necrotizing enterocolitis (NEC). This study was designed to investigate the role of the PAF-degrading enzyme acetylhydrolase(PAF-AH) in a neonatal rat model of NEC. To study the absorption, localization, and activity of human recombinant PAF-AH (rPAF-AH), newborn rats were treated with enteral rPAF-AH, and plasma and intestines were sampled at 8 and 24 h for determination of PAF-AH enzyme activity and rPAF-AH concentration using a specific enzyme-linked immunoassay. To study the effect of rPAF-AH on neonatal NEC, rats were treated with rPAF-AH via the enteral route every 3 h, and then subjected to formula feeding and asphyxia per an established neonatal rat protocol for NEC. Pretreatment with enteral rPAF-AH significantly reduced the incidence of NEC compared with controls (6/26versus19/26,p< 0.001). We found that enteral rPAF-AH administration resulted in significant intestinal PAF-AH activity but no circulating PAF-AH activity despite immunohistochemical localization of the administered rPAF-AH to the intestinal epithelial cells. These findings suggest that rPAF-AH is functional and stable in the gut of neonatal rats. We conclude that enteral administration of rPAF-AH remains locally active and reduces the incidence of NEC in our experimental animal model.

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID