摘要:

We investigated the effects of prenatal dexamethasone treatment on indicators of cardiac maturation: heart weight/body weight ratios, myosin heavy chain (MHC) expression, cell proliferation, and extracellular matirix. We administered dexamethasone, a synthetic glucocorticoid (approximately 48μg/d, 3-wk slow release pellets), to pregnant rats (n= 8) beginning at 17 d postconception. Control dams were unmanipulated (n= 8). After approximately 4-5 d of dexamethasone exposure, hearts were collected from neonatal rats (12-24 h after birth). The prenatal dexamethasone treatment produced smaller pups with larger heart/body weight ratios, accompanied by a higher proliferative index and a reduction in extracellular matrix in the ventricles (with lowest values in the septal region) compared with control pups. We also report that, although there were no sex differences in body mass or heart and heart/body weight ratios, females had a greater proportion of cells synthesizing DNA in the heart. In addition, ventricles of male pups treated with dexamethasone contained lower levels of α-MHC mRNA, as reflected in a sex by treatment interaction. The changes in each parameter are consistent with delayed maturation. Our findings suggest that exposure to excess glucocorticoidsin uterocan affect cardiac development in potentially detrimental ways and that assessment of cardiac function should be closely monitored when such circumstances arise.Abbreviations: MHC,myosin heavy chain;BrdU,bromodeoxyuridine;ECM,extracellular matrix

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:

Severe neonatal aspiration of meconium is frequently complicated by fatal pulmonary hypertension. The protective effect of an i.v. bolus of methylprednisolone on meconium aspiration-induced hypertensive lung injury was studied in anesthetized pigs with adapted lung circulation. Eleven 10-wk-old pigs received 3 mL/kg 20% human meconium via the endotracheal tube. Five of them were pretreated with 30 mg/kg methylprednisolone 30 min before aspiration. Ventilator settings were adjusted to keep arterial Po2above 8 kPa and arterial Pco2below 5 kPa. Meconium insufflation induced a biphasic pulmonary pressor response during the 6 h follow-up. Methylprednisolone tended to prevent the early (0-1 h) increase in pulmonary artery pressure and inhibited significantly the second phase (1-6 h) progressive rise in pulmonary artery pressure and pulmonary vascular resistance. This inhibition of resistance increase was most profound in the postarterial segment of the lung circulation, as determined by pulmonary artery occlusion. Additionally, the methylprednisolone pretreated group demonstrated a significant decrease in venous admixture together with improved oxygenation during the late phase after the insult, and further showed evidence of diminished lung edema formation. Although meconium aspiration-induced fall in blood leukocyte concentration was inhibited by methylprednisolone pretreatment, no histologic difference was found in pulmonary leukocyte sequestration. Our results thus show that in adapted porcine lungs methylprednisolone pretreatment improves oxygenation and attenuates the meconium aspiration-induced pulmonary hypertensive response by preventing the increase in the postarterial resistance.Abbreviations: MPAP,mean pulmonary artery pressure;PWP,pulmonary wedge pressure;CVP,central venous pressure;PAOP,pulmonary arterial occlusion pressure;MABP,mean arterial blood pressure;CO,cardiac output;PVR,pulmonary vascular resistance;Ra, pulmonary arterial resistance;Rv, pulmonary postarterial resistance;˙Qva/˙Qt, venous admixture;Fio2, fraction of inspired oxygen

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

To investigate whether nitric oxide (NO) is involved in surfactant-induced systemic and pulmonary vasodilatation in newborn piglets with surfactant deficiency, 2-6-d-old piglets were subjected to repeated saline lung lavages. They were then randomly assigned to one of two groups (seven in each group): theNω-nitro-L-arginine methyl ester (L-NAME) group received 3 mg/kg L-NAME i.v. 45 min before endotracheal instillation of 200 mg/kg porcine surfactant; the saline group received saline i.v. at the same time point, and instillation of 200 mg/kg surfactant. Mean arterial blood pressure, systemic vascular resistance, pulmonary arterial pressure, and pulmonary vascular resistance increased significantly after injection of L-NAME (allp< 0.01), whereas the cardiac index decreased significantly (p< 0.05). Saline injection did not change any variable. Significant decreases in mean arterial blood pressure (from a mean± SD of 66 ± 10 to 53 ± 9 mm Hg,p< 0.01), pulmonary arterial pressure (from 29 ± 6 to 23 ± 6 mm Hg,p< 0.01), and systemic vascular resistance (from 0.40 ± 0.13 to 0.33 ± 0.12 mm Hg/mL/min/kg,p< 0.05) were observed only in the saline group after surfactant instillation, whereas the decrease in pulmonary vascular resistance was not significant after surfactant instillation (p= 0.06). In contrast to the saline group, these variables were not modified in the L-NAME group after surfactant instillation. We conclude that the vasodilatory effect of porcine surfactant instillation in newborn piglets with surfactant deficiency is associated with activation of NO synthase.Abbreviations: a/A ratio,arterial/alveolar ratio of oxygen tension;CO,cardiac output;CVP,central venous pressure;Fio2, fraction of inspired oxygen;I:E ratio,ratio between inspiration and expiration times;L-NAME,Nω-nitro-L-arginine methyl ester;MABP,mean arterial blood pressure;NO,nitric oxide;Paco2, arterial tension of carbon dioxide;Pao2, arterial tension of oxygen;RDS,respiratory distress syndrome

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The effects of breathing normal saline, salmeterol, fenoterol, ipratropium bromide, or formoterol, and of i.v. infusion of theophylline on oxygen consumption (˙Vo2), carbon dioxide production (˙Vco2), minute ventilation (˙Ve), heart and respiratory rates, and end-tidal carbon dioxide tension (PETco2) have been defined in 10 anesthetized, intubated rhesus monkeys (mean age 7.0 y, weight 10.2 kg).˙Vo2increased over control by +17.1% after salmeterol (p< 0.001), +33.3% after fenoterol (p< 0.001), +23.7% after formoterol (p< 0.001), +3.9% after theophylline (p< 0.01), but did not change after ipratropium bromide and normal saline. Ve increased by 63.0% after fenoterol (p< 0.001), 49.8% after formoterol (p< 0.001), 31.7% after salmeterol (p< 0.01), and 29.7% after theophylline (p< 0.001), but not after ipratropium bromide or normal saline. Heart rate response was greatest after fenoterol, formoterol, and salmeterol, respectively. PETco2dropped dramatically after theophylline (-15.7%,p< 0.001), but not at all with any of the inhaled β2-adrenoceptor agonists. In seven animals, salbutamol (albuterol) caused an increase in ˙Ve and˙Vo2of 50.1% and 45.9%, respectively, whereas in the presence of aβ2-adrenoceptor antagonist {racemic or (+/-)-propranolol (0.1 mg/kg i.v.)}, inhaled salbutamol (2.5 mg/mL for 10 min) could not increase˙Ve (+6.2%,p> 0.05) and ˙Vo2(+1.6%,p> 0.05). The increase in ˙Vo2and ˙Ve after administration of β2-agonists may be partly the result of direct stimulation of the respiratory center and partly a response to increased metabolic rate. The dramatic increase in ˙Vo2and ˙Ve after salbutamol was suppressed in the presence of propranolol, which is consistent with aβ-receptor-mediated mechanism.Abbreviations: PETco2, end-tidal carbon dioxide tension;Vco2, carbon dioxide production;˙Ve,minute ventilation;˙Vo2, total body oxygen consumption;˙Vo2resp, oxygen cost of breathing;Sao2, arterial oxygen saturation

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Changes in arterial Pco2(Paco2) and body temperature normally occurring at the moment of birth may play a role in the initiation and maintenance of continuous breathing. To clarify these mechanisms, five chronically instrumented fetal lambs were connected to an extracorporeal membrane oxygenation (ECMO) system. ECMO was initiatedin uteroat a flow rate sufficient to support the fetus totally, the umbilical cord was occluded, and the fetuses were delivered into a warm isotonic saline bath. Breathing activity was present periodically before connection to the ECMO system and on ECMO during fetal normocapnia and normoxia. Near delivery there were no breathing movements, because all ewes were in labor. After delivering the fetuses into the warm saline bath, breathing movements remained episodic, being absent during high voltage electrocortical activity, whereas fetal Paco2remained constant. However, after 36-192 min, breathing activity became present continuously in all animals, at a time when fetal central temperature decreased. Once initiated, continuous breathing could be stopped by reducing the Paco2. We conclude that maintenance of fetal Paco2and a slow decrease in central temperature after cord occlusion delays the establishment of continuous breathing, and that the level of Paco2is important in the maintenance of breathing activity during early postnatal life.Abbreviations: ECMO,extracorporeal membrane oxygenation;HV,high voltage;LV,low voltage;ECoG,electrocortical activity;EMG,electromyogram

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Recent reports suggest an important role for pulmonary surfactant in maintaining the patency of narrow conducting airways. The hypothesis that surfactant dysfunction is an important factor in respiratory syncytial virus(RSV) infection was tested in a mouse model. Mice, inoculated with either a low or a high dose of RSV, were subjected to bronchoalveolar lavage (BAL), and the fluids were analyzed for percentage of inflammatory cells and concentrations of proteins and phospholipids. After concentration of the surfactant by centrifugation, its function was analyzed with a capillary surfactometer. RSV infection resulted in a dose-dependent disruption of surfactant function (p< 0.0001). BAL fluid supernatants were added to calf lung surfactant extract (CLSE) to examine whether surfactant inhibiting agents were present. Indeed, BAL fluid supernatants of RSV-infected mice disrupted the normal function of calf lung surfactant extract in a dose dependent way (p< 0.0001), indicating the presence of inhibitors. Protein concentrations were increased in BAL fluids of RSV-infected miceversuscontrol mice (p< 0.0001), and were inversely related to surfactant function (r= -0.44,p= 0.0004), suggesting an inhibitory effect of proteins. Protein concentration also correlated with the percentage of inflammatory cells(r= 0.51,p= 0.004). Phospholipid concentrations were not affected by the RSV infection. The results of these studies strongly suggest that a disruption of pulmonary surfactant function, most likely due to inhibition from inflammatory proteins, is important for the pathophysiology of RSV infection.Abbreviations: BAL,bronchoalveolar lavage;CLSE,calf lung surfactant extract;pfu,plaque-forming unit;RSV,respiratory syncytial virus

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Hypoxia-induced brain cell membrane lipid peroxidation can be caused by free radicals that are produced during hypoxia. Recently, the production of nitric oxide (NO), a free radical, has been shown to be increased during cerebral hypoxia-ischemia. The present study tested the hypothesis that inhibition of NO synthase (NOS) reduced hypoxia-induced modifications of Na+,K+-ATPase activity, lipid peroxidation, and[3H]MK-801 binding to theN-methyl-D-aspartate (NMDA) receptor in cerebral cortical tissue of newborn piglets. Studies were performed in 26 newborn piglets. Cerebral NOS was inhibited by the i.v. administration of 25 or 50 mg/kgNω-nitro-L-arginine(NNLA) over 30 min. Control animals received normal saline. Six groups of piglets were thus created (normoxia, no NNLA; normoxia + NNLA 25 mg/kg; normoxia + NNLA 50 mg/kg; hypoxia, no NNLA; hypoxia + NNLA 25 mg/kg; hypoxia + NNLA 50 mg/kg). One hour after the start of NNLA or saline infusion, hypoxia was induced by lowering the Fio2to 0.07 in the three hypoxia groups, whereas in the three other groups normoxia was maintained. After 60 min of hypoxia, the brain was taken out and frozen. NOS activity, Na+,K+-ATPase activity, conjugated dienes, and [3H]MK-801 binding to the NMDA receptor of cerebral cortical tissue were determined. NOS activity was reduced to 34% of its baseline value with NNLA 25 mg/kg, and to 19-27% of its baseline value with NNLA 50 mg/kg, respectively. Administration of NNLA did neither significantly alter the hypoxia-induced production of conjugated dienes, indicating lipid peroxidation nor the decrease of Na+,K+-ATPase activity after hypoxia. [3H]MK-801 binding studies of the NMDA receptor, however, showed that NNLA preservedBmaxandKdafter hypoxia. We conclude that inhibition of NOS does not change the hypoxia-induced decrease of Na+,K+-ATPase activity and production of conjugated dienes in brain cell membranes. Inhibition of NOS preserved the binding of[3H]MK-801 to the NMDA receptor after hypoxia.Abbreviations:Bmax, maximum number of receptors;NMDA,N-methyl-D-aspartate;NNLA,Nω-nitro-L-arginine;NO,nitric oxide;NO+, nitrosonium ion;NOS,nitric oxide synthase

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Although the pathogenesis of necrotizing enterocolitis remains uncertain, ischemia appears to be an important contributing factor to the development of this disorder. Reperfusion plays a major role in ischemia-related injury, and oxygen free radicals produced during reperfusion most likely contribute to the injury. These oxidants can be generated during prostanoid metabolism, which increases during reperfusion of ischemic gut in adult subjects. The present study was designed to:1) examine the effects of superior mesenteric artery occlusion,e.g.ischemia and reperfusionin vivoon the development of histopathologic intestinal injury;2) determine whether products of arachidonic acid metabolism,e.g.prostanoids are increased during reperfusion of ischemic gut; and3) determine whether oxygen free radical scavengers attenuate the injury in newborn pigs. Chronically catheterized placebo-pretreated newborn pigs exposed to ischemia-reperfusion, placebo-pretreated nonischemic control pigs, and polyethylene glycol-superoxide dismutase (SOD) plus polyethylene glycol-catalase (CAT)-pretreated, ischemic pigs were studied by examining changes in intestinal circulation, oxygenation, prostanoids, and tissue injury. In the placebo-pretreated pigs, intestinal blood flow decreased to very low levels during superior mesenteric artery occlusion. During reperfusion, blood flow increased, but remained below baseline. After ischemia, oxygen uptake returned to values that were similar to baseline. Intestinal efflux of the vasodilator 6-keto-prostaglandin F1αwas evident (p< 0.05versusno or zero efflux) during early reperfusion. Histopathologic scoring of terminal ileal samples showed significant mucosal necrosis, surface epithelial disruption, lamina propria congestion and hemorrhage, submucosal hemorrhage, edema, and increases in cells compared with the placebo-pretreated nonischemic pigs. In the SOD plus CAT-pretreated ischemic pigs, changes in intestinal blood flow, oxygen uptake, 6-keto-prostaglandin F1αefflux, and the pattern of the ileal tissue injury did not differ significantly from the placebo-pretreated ischemic pigs. In summary, superior mesenteric artery occlusion for 1 h and reperfusion for 2 h resulted in severe intestinal ischemia, early postocclusive limited increases in intestinal perfusion and oxygen uptake, efflux of vasodilating prostanoids during early reperfusion, and signs of ischemic tissue injury in the placebo- and SOD plus CAT-pretreated pigs. This study demonstrates that, after superior mesenteric artery occlusion and reperfusion, severe intestinal tissue injury is detectedin vivo,prostanoid efflux increases, and SOD plus CAT given just before occlusion does not attenuate the extent of injury in newborn pigs.Abbreviations: ANOVA,analysis of variance;Cao2, arterial oxygen content;-˙V,intestinal efflux;+˙V,intestinal influx;˙Vo2, oxygen uptake;CAT,catalase;SOD,superoxide dismutase;Cpvo2, portal venous oxygen content;PG,prostaglandin

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Previous investigations in rats older than 7 d have shown that apical sodium-dependent bile acid transport in the ileum is abruptly expressed at the time of weaning, whereas it is constitutively expressed in the kidney. The current study was designed to characterize the expression of sodium-dependent bile acid transport in late gestation and in the immediate postnatal period in the rat. Sodium-dependent bile acid transport was measured by rapid filtration using [3H]taurocholate and crude brush border membrane vesicles. Apica sodium-dependent bile acid transporter (ASBT) and ileal lipid binding protein(ILBP) expression were analyzed by Western and Northern blotting. Ileal bile acid content was measured by gas chromatography/mass spectrometry. In the ileum significantly greater sodium-dependent taurocholate uptake was measured in fetal d 22 (E22) membrane vesicles compared with postnatal d 7 (E22 17.0± 5.7, P7 3.9 ± 2.1 pmol/mg/60 s mean ± SD,n= 3,p= 0.02). Gas chromatography/mass spectrometry revealed significant quantities of ileal bile acids at E22. Western and northern blotting of fetal ileum revealed ASBT but not ILBP. ASBT expression was suppressed by P7 and then reinduced by P21, whereas ILBP appeared to be first expressed postnatally. In contrast ASBT expression in the kidney was less age-dependent. Therefore, it appears that functional expression of the ASBT gene in the rat ileum is biphasic with a prenatal onset of expression, followed by repression in the early postnatal period and then marked reinduction at weaning.Abbreviations: ASBT,apical sodium-dependent bile acid transporter;ILBP,ileal lipid binding protein;E,embryonic (fetal) day; P, postnatal day;BBMV,brush border membrane vesicle;GC/MS,gas chromatography/mass spectrometry

ISSN:0031-3998    

出版商:OVID    

年代:1997

数据来源: OVID