ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Near infrared spectroscopy (NIRS) shows large changes in cerebral oxyhemoglobin (Hbo2), deoxyhemoglobin (Hb), and oxidation state of cytochromeaa3(Cyto2) in infants undergoing cardiopulmonary bypass and deep hypothermic circulatory arrest (CPB-DHCA). To evaluate the physiologic significance of these clinical NIRS measurements, we applied the technique in a piglet model of CPB-DHCA. After an initial stabilization period on CPB, animals (n= 8) were cooled to 15°C, subjected to DHCA for 1 h, then reperfused with rewarming and monitored for 180 min. NIRS measurements were compared with determinations of cerebral blood flow (CBF). During cooling, Cyto2decreased markedly, whereas Hbo2increased. DHCA was associated with a sharp decrease in Hbo2, a corresponding increase in Hb, and a smaller, less consistent further decrease in Cyto2. NIRS measurements recovered toward baseline with reperfusion. CBF decreased during cooling and recovered to baseline levels with reperfusion. These findings are consistent with existing human data and show that1) cooling is associated with increased oxygenation of cerebral hemoglobin despite a reduction in CBF;2) Cyto2becomes more reduced during cooling, consistent with a net cellular oxygen deficit; and3) DHCA is associated with rapid cerebral hemoglobin deoxygenation and a small further reduction of Cyto2.Abbreviations: CPB,cardiopulmonary bypass;CA,cardiac arrest;DHCA,deep hypothermic circulatory arrest;CBF,cerebral blood flow;MAP,mean arterial blood pressure;NIRS,near infrared spectroscopy;dpf,differential path length factor;Hbo2, oxygenated Hb;Hb,deoxygenated Hb;HbT,total Hb;Cyto2, oxidation state of cytochromeaa3;MRS,magnetic resonance spectroscopy;PCr,phosphocreatine;pHi, intracellular pH

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Platelet-activating factor (PAF) is overproduced in ischemic brain. Although postischemic PAF antagonist administration protects the mature brain in some models, little is known about the effects of PAF antagonists in the immature brain. We hypothesized that the PAF antagonist BN 52021 would attenuate perinatal cerebral hypoxic-ischemic injury. To elicit focal hypoxic-ischemic brain injury, 7-d-old (P7) rats (n= 111) underwent right carotid ligation, followed by 2.5-3.25 h of hypoxia (fractional concentration of inspired O2= 0.08). BN 52021 neuroprotection was evaluated in three groups of experiments:1) 25 mg/kg/dose, 0 and 2 h posthypoxia;2), 25 mg/kg/dose immediately before and 1 h after hypoxia; and3) posthypoxia-ischemia treatment with BN 52021 12.5, 25, or 50 mg/kg/dose in 2 doses 0 and 2 h after hypoxia. All experiments included concurrent vehicle-injected controls. To quantitate severity of injury, bilateral regional cross-sectional areas (groups 1 and 2) or hemisphere weights (group 3) were evaluated on P12. Both preand posthypoxic treatment with BN 52021 (25 mg/kg/dose, two serial doses) decreased the incidence of cerebral infarction from 90% to about 30% (p< 0.02, Fisher's exact test). Measurement of cross-sectional areas confirmed neuroprotection and indicated some benefit of pre- over posthypoxic-ischemic treatment in hippocampus and cortex. Over the dose range tested, the neuroprotective effect of BN 52021 administration was not dose-dependent. In contrast, BN 52021 did not attenuateN-methyl-D-asparate-induced hippocampal excitotoxic injury in P7 rats. Either prophylactic or“rescue” administration of PAF antagonists decreases the incidence and severity of brain injury associated with an episode of perinatal cerebral hypoxia-ischemia.Abbreviations: EAA,excitatory amino acid;PAF,platelet-activating factor;P7, P8, P12,postnatal d 7, 8, 12;Fio2, fractional concentration of inspired oxygen;NMDA,N-methyl-D-aspartate;ANOVA,analysis of variance;MK-801,(+)-5-methyl-10,11-dihydro-5H-dibenzo{a,d} cyclohepten-5-10-imine maleate;NBQX,2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Bilirubin neurotoxicity can be mediated by numerous mechanisms due to its increased permeability in neuronal membranes. The present study tests the hypothesis that a prolonged bilirubin infusion modifies theN-methyl-D-aspartate (NMDA) receptor/ion channel complex in the cerebral cortex of newborn piglets. Studies were performed in seven control and six bilirubin-exposed piglets, 2-4 d of age. Piglets in the bilirubin group received a 35 mg/kg bolus of bilirubin followed by a 4-h infusion (25 mg/kg/h) of a buffer solution containing 0.1 N NaOH, 5% human albumin, and 0.055 Na2HPO4with 3 mg/mL bilirubin. The final mean bilirubin concentration in the bilirubin group was 495.9 ± 85.5 μmol/L (29.0± 5.0 mg/dL). The control group received a bilirubin-free buffer solution. Sulfisoxazole was administered to animals in both groups. P2membrane fractions were prepared from the cerebral cortex. [3H]MK-801 binding assays were performed to study NMDA receptor modification. TheBmaxin the control and bilirubin groups were 1.20 ± 0.10 (mean ± SD) and 1.32 ± 0.14 pmol/mg protein, respectively. The value forKdin the control brains was 6.97± 0.80 nM compared with 4.80 ± 0.28 nM in the bilirubin-exposed brains (p< 0.001). [3H]Glutamate binding studies did not show a significant difference in theBmaxandKdfor the NMDA-specific glutamate site in the two groups. The results show thatin vivoexposure to bilirubin increases the affinity of the receptor (decreasedKd) for [3H]MK-801, indicating that bilirubin modifies the function of the NMDA receptor/ion channel complex in the brain of the newborn piglet. We speculate that the affinity of bilirubin for neuronal membranes leads to bilirubin-mediated neurotoxicity, resulting in either short- or long-term disruption of neuronal function.Abbreviations: NMDA,N-methyl-D-aspartate;Bmax, total number of receptors;Pao2, partial pressure of arterial O2;Paco2, partial pressure of arterial CO2

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Nestin is an intermediate filament protein found in CNS progenitor cells. Nestin reappears in CNS tumor cells and reactive astrocytes after CNS injury. In this study we investigated whether nestin could be detected in the cerebrospinal fluid (CSF) of newborn infants and whether expression levels change with gestational age (GA) and/or brain injury. Using Western blot analysis, we examined the expression of nestin in the CSF of newborn infants(GA 25-42 wk) with asphyxia (n= 14), periventricular leukomalacia and peri(intra)ventricular hemorrhage (n= 7), and in a control group (n= 11). Protein extract from the periventricular brain tissue of a 1-wk-old infant was also analyzed. Nestin was detected in all the CSF samples and in the protein extract from the periventricular brain tissue. Although the CSF levels of nestin expression did not change with increasing GA, the asphyxia group had significantly lower levels of nestin in the CSF. An unexpected finding was that brain-derived nestin had an apparent molecular mass of approximately 240 kD, whereas all analyzed CSF samples contained two nestin-immunoreactive proteins at 200 and 220 kD. Experimental deglycosylation of the 240-kD form reduced the molecular mass to 220 kD, indicating that nestin undergoes a specific deglycosylation upon release into the CSF.Abbreviations: CSF,cerebrospinal fluid;IF,intermediate filament;PVL,periventricular leukomalacia;PIVH,peri(intra)ventricular hemorrhage;GA,gestational age;PCR,polymerase chain reaction

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

In the neonatal lung, hyperoxic exposure is associated with induction of various genes and critical antioxidants. Heme oxygenase, specifically the HO-1 isoenzyme, is regulated in oxidant stress and may also serve to limit oxidative damage. However, it is not known whether neonatal lung HO-1 is regulated in hyperoxia specifically and, if so, what type of regulation occurs. Therefore, we attempted to answer these questions using newly born(< 12 h) Wistar rats exposed to hyperoxia for 3 d. Neonatal rat lungs were evaluated daily for total HO activity, immunore-active HO-1 protein, and steady state levels of HO-1 mRNA and compared with air-exposed controls. In neonatal rats, we noted an increased lung HO activity after 3 d of hyperoxic exposure. Additionally, evaluation of HO activity after immunoprecipitation of HO-1 protein suggested that HO-1 contributed most of the increase in lung total HO activity observed in hyperoxia. Nonetheless, we did not see a significant difference in immunoreactive HO-1 protein in neonatal lungs after 3 d of hyperoxic exposure, although we did so on d 2. Also, in contrast with previous reports, we did not detect any significant differences in steady state levels of HO-1 mRNA on any day of hyperoxic exposure compared with air. We therefore conclude that neonatal rat lung HO-1 is regulated in hyperoxia and speculate that the regulation of neonatal lung HO-1 occurs by posttranscriptional mechanisms, at least within the first days of hyperoxic exposure.Abbreviations: HO,heme oxygenase;TBS,Tris-buffered saline;GAPD,glyceraldehyde-3-phosphate dehydrogenase;Do, preexposure control;CCR,NADPH-cytochromec2P450 reductase;PCR,polymerase chain reaction;UVA,UV long wavelength

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Previous studies have shown that i.v. endotoxin infusion causes gastrointestinal dysfunction and intestinal injury in piglets. The aim of this study was to investigate the effects of endotoxin on intestinal myoelectric activity in newborn swine and to correlate this with gastrointestinal and hemodynamic events. Three pairs of electrodes were implanted in the jejunal wall of piglets, and after recovery, intestinal myoelectric activity was continuously recorded in the conscious, fasted condition. The intestinal myoelectric activity on the control day showed regular, repeating migrating myoelectric complex (MMC) cycles, each of which was composed of the classic phases I, II, and III. Mean cycle duration was 67.0 ± 18.7 min(±SD), and phase III comprised 9.1 ± 2.2% of each cycle. On the next day, infusion of 30 μg/kg endotoxin caused an initial, prolonged quiescent period and delayed the appearance of the first postendotoxin phase III complex. After the quiescent period, there was a period of irregular spiking activity followed by several shortened MMC cycles (47.9 ± 22.7 min,p< 0.01versuscontrol) with a prolongation of the percentage of time spent in phase III (15.4 ± 11.3%,p< 0.01). Endotoxin thus produced biphasic alterations in intestinal myoelectric activity characterized by an initial quiescence followed by increased gastrointestinal smooth muscle activity. Animals developed diarrhea, hypotension, and tachycardia about 1 h after endotoxin infusion in temporal association with increased spiking activity and MMC cycling. These studies are the first to show this biphasic response to endotoxin.Abbreviations: IMA,intestinal myoelectric activity;MMC,migrating myoelectric complex;Psa,systemic artery pressure;mPsa,mean systemic artery pressure

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

The release of endogenous vasoconstrictors together with changes in the vascular responses are central to the pathophysiology of sepsis. The effects ofin vitroincubation for 20 h with heat-killed group B Streptococcus (GBS, 3 × 107colonyforming units mL-1) on the vasoconstrictor responses to noradrenaline (NA, 10-8to 10-4M), the thromboxane A2analog 9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F2α(U46619; 10-10M to 10-6M) and endothelin-1 (ET-1, 10-11to 3 × 10-9M) were evaluated on isolated intrapulmonary and mesenteric arteries from 10-17-d-old piglets. The incubation with GBS reduced the maximal contractile response to NA and ET-1 (p< 0.01) in both arteries. The nitric oxide (NO) synthase (NOS) inhibitorNω-nitro-L-arginine methyl ester (L-NAME; 10-4M) completely reversed this hyporesponsiveness. GBS-treated mesenteric arteries also showed a significant reduction of the maximal contractions induced by U46619 (p< 0.05) and this effect was inhibited by 10-4M L-NAME. In contrast, the maximal contractile responses to U46619 were similar in control and in GBS-treated pulmonary arteries. Addition of L-NAME did not modify the contractile responses to U46619 in GBS-treated pulmonary arteries. In conclusion, GBS-treated systemic arteries from neonatal piglets showed decreased responses to NA, U46619, and ET-1 due to enhanced NO release. GBS-treated pulmonary arteries also exhibited decreased responses to NA and ET-1 but not to U46619. Induction of NOS in vascular smooth muscle may play a key role in the hypotension and loss of systemic vascular responsiveness that occurs in GBS sepsis. The absence of pulmonary hyporesponsiveness to U46619 may partially explain the coexistence during sepsis of pulmonary hypertension and lung NOS induction.Abbreviations: GBS,Group B Streptococcus;LPS,lipopolysaccharide;ET-1,endothelin-1;TXA2, thromboxane A2;NO,nitric oxide;iNOS,inducible nitric oxide synthase;NA,noradrenaline;U46619,9,11-dideoxy-11α,9α-epoxymethanoprostaglandin F2α;L-NAME,Nω-nitro-L-arginine methyl ester;cfu,colony-forming units

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID

摘要:

Passage of meconiumin uteroand subsequent pulmonary aspiration of meconium admixed with amniotic fluid is a major cause of neonatal respiratory distress. Airway clearance is the first defense of the lung, and clearance is dependent on the bulk physical (rheologic) as well as the surface properties of airway material. We therefore evaluated the surface adhesive properties and the transport properties of freshly passed meconium and of two dilutions of reconstituted, blended, meconium as used to mimic the effect of meconium passage into the amniotic fluid in animal models of meconium aspiration syndrome. Reconstituted and fresh meconium had similar physical and transport properties, including an extremely high interfacial (adhesion) tension and very poor transportability by either airflow or cilia. The similarities between the freshly passed and reconstituted meconium suggest that the latter is an adequate substitute for use in animal models of meconium aspiration syndrome. The high adhesiveness of meconium suggests a potential role for surfactant administration as an adhesive to improve airway clearance after meconium aspiration.Abbreviations: MCTR,mucociliary transportability;CTR,cough (airflow) transportability

ISSN:0031-3998    

出版商:OVID    

年代:1996

数据来源: OVID