摘要:

Cerebral hypoxia-ischemia remains a major cause of acute perinatal brain injury, leading ultimately to neurologic dysfunction manifest as cerebral palsy, mental retardation, and epilepsy. Research in experimental animals over the past 10 or more years has expanded greatly our understanding of the cellular and molecular events that occur during a hypoxic-ischemic insult to brain, and recent discoveries have suggested that metabolic pertubations arising in the recovery period after resuscitation contribute substantially to the nature and extent of neuronal destruction. The review focuses on those neurochemical processes responsible for the maintenance of cellular homeostasis and how these mechanisms fail in hypoxia-ischemia to culminate in brain damage. Knowledge of these critical events has opened new avenues of potential therapy for the fetus and newborn infant subjected to cerebral hypoxia-ischemia to prevent the serious delayed effects of perinatal brain injury.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

To evaluate the relationship between brain blood flow and ventilatory response to hypoxia, seventeen sedated, spontaneously breathing newborn piglets were studied. Minute ventilation (&OV0312;E) was measured by pneumotachograph, cardiac output by thermodilution and total brain and brain stem blood flows with radiolabeled microspheres. Measurements were performed while the animals were breathing room air and after 10 min of hypoxia induced by breathing 10% O2. Two patterns of ventilatory response to hypoxia were observed in the study animals. All animals increased&OV0312;Eduring the 1st min of hypoxia, but nine (mean ± SD; age 5 ± 1.3 d; wt 1828 ± 437 g) sustained increased &OV0312;Eafter 10 min of hypoxia (↑&OV0312;Egroup). The remaining eight animals (age 5 ± 1.2 d; wt 1751 ± 168 g) had decreased &OV0312;Eat 10 min of hypoxia to values less than their room air baseline (↓&OV0312;Egroup). The decrease in PaO2during hypoxia was similar in both groups, however the PaCO2decreased significantly only in the ↑&OV0312;Egroup. Although cardiac output increased significantly during hypoxia in both groups, the values during normoxia and hypoxia were lower in the ↓&OV0312;Egroup (p<0.001). Arterial blood pressure increased significantly during hypoxia only in the ↑&OV0312;Egroup. The increase in total brain and brain stem blood flows with hypoxia was similar in both groups, despite the two different patterns of ventilatory response to hypoxia. These data suggest that in this animal model the distinct patterns of ventilatory response to hypoxia are not related to the changes in total brain or brain stem blood flows that occur during hypoxia.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Cytotoxic free radicals are generated during cerebral hypoxia-ischemia and reperfusion. We studied the efficacy of allopurinol, a xanthine oxidase inhibitor and free radical scavenger, in reducing posthypoxic-ischemic damage in the developing brain of 7-d-old rat pups. Hypoxic- ischemic injury to the right cerebral hemisphere was produced by ligation of the right common carotid artery followed by 3 h of hypoxia with 8% oxygen. Thirty to 45 min before the hypoxia, the rats received either allopurinol (dose=130-138 mg/kg) or an equal vol of saline (0.2 mL). Some pups were killed at 42 h of recovery for measurement of cerebral hemispheric water content, whereas others were killed at 30 or more d for neuropathologic examination. A total of 18 allopurinol treated rats had significantly less water content in the right hemisphere (89.07 ± 0.32%) than 23 saline-treated animals (91.64 ± 0.25%, mean ± SEM,p<0.0001). Rank scoring of neuropathologic alterations revealed that the allopurinol treated rats were less damaged (p=0.001). Only two of 13 brains from the allopurinol group suffered infarction compared to 10 of the 14 saline-treated animals. The results indicate that allopurinol reduces both cerebral edema and the extent of perinatal hypoxic-ischemic brain damage.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We have investigated the impaired secretion response of neonatal platelets. We compared the response of washed neonatal and adult platelets to thrombin and collagen, and to specific activators of calcium flux (inositol trisphosphate) and protein kinase C activation (oleoylacetyl glycerol). Neonatal platelets show no impairment of aggregation, secretion of [14C]serotonin or phosphorylation of specific intracellular proteins in response to thrombin, inositol trisphosphate, or oleoyl-acetyl glycerol. However, neonatal platelets have a markedly decreased response to collagen. To further evaluate this deficient response, we examined specific aspects of the collagen activation pathway. Collagen-platelet interaction as measured by adhesion of platelets to collagen-coated dishes showed no difference in adhesion of neonatal platelets compared to adult controls (20.1 ±11.6versus18.6 ± 9.3%). The presence of GPIa/ Ila, a Mg2+-dependent collagen receptor, was evaluated by flow cytometric analysis of binding of fluorescein-tagged monoclonal antibody, 6F1 (directed against GPIa/IIa). There was no difference either in the percent of platelets that bound antibody (80versus81%) or in the mean fluorescence intensity of the adult and neonatal samples. Phosphoinositide hydrolysis was decreased in neonatal platelets in response to collagen but normal in response to thrombin. Neonatal platelets released more arachidonic acid than adult platelets in response to thrombin (29.5 ± 3.2versus19.6 ± 1.8%) but less than adult platelets in response to 10 µg/mL collagen (3.2 ± 1.1versus9.3 ± 3.0%). Thromboxane B2production was also decreased in response to collagen (52.7 ± 12.6versus101.4 ± 18.7 ng/mL). These results suggest that the deficient collagen response in neonatal platelets may lie in transduction of the collagen signal to phospholipases A2and C.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Despite the serious pulmonary manifestations of early onset group B streptococcal (GBS) sepsis, it is not known whether the organism distributes into lung tissue and whether adverse pulmonary hemodynamic abnormalities relate to an interaction between the organism and target cells in the pulmonary vascular bed. Accordingly, this study evaluated the distribution and fate of GBS in the lung, liver, and spleen of anesthetized infant piglets and in isolated, salt solution-perfused piglet lung preparations. GBS were radiolabeled with111Indium-oxine and infused at a dose of 108organisms/kg/min for 15 min into anesthetized piglets ranging in age from 5-10 d. Forty-five min after termination of the infusion, animals were killed and specimens of lung, liver, spleen, and blood were excised and the relative deposition and viability of GBS were determined. Most of the recovered bacteria were detected in the lung (53.2 ± 3.9%) followed by the liver (41.4 ± 2.0%) and spleen (2.2 ± 0.38%). GBS detected in the blood was estimated to be only 3.2 ± 1.0% of the infused dose. Viability of GBS was least in the lung (21.4 ± 2.6%) relative to the liver (45.7 ± 11.2%) and spleen (83.4 ± 19.5%). After a 60-min GBS infusion, transmission electron microscopy localized the organism within pulmonary intravascular macrophages in the lung; there was no evidence for bacterial interaction with either neutrophils or endothelial cells. In the liver, GBS was found exclusively in Kupffer cells. In isolated piglet lungs perfused at a constant flow rate with blood-free physiologic salt solution, GBS (106to 108organisms/mL) provoked concentration-dependent increases in pulmonary vascular resistance. Transmission electron microscopic examination of isolated lungs indicated that GBS was localized within pulmonary intravascular macrophages, again with no apparent intractions between the organism and other cellular residents of the pulmonary vascular bed. These results indicate that GBS distributes into lung and liver where resident intravascular phagocytes, possibly pulmonary intravascular macrophages and Kupffer cells, respectively, contribute to killing of the organism. In addition, because GBS evokes pulmonary hypertension in isolated piglet lung preparations, it appears that cardiopulmonary disturbances in the intact animal could be initiated by a direct interaction between GBS and resident lung cells without obligatory participation by other organ systems.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Both thromboxane A2and oxygen-derived free radicals appear to play central roles in group B streptococcus (GBS)-induced pulmonary hypertension in piglets. This study tested the hypothesis that GBS promotes oxygen radical-dependent thromboxane accumulation and pulmonary hypertension in infant piglets. Piglets 4-12 d old were anesthetized and prepared for assessment of pulmonary arterial pressure and arterial blood gases. In control animals, GBS (108organisms/kg/min for 15 min) increased mean pulmonary artery pressure by 30 ± 1.5 torr and reduced arterial PO2by 100 ± 20 torr. Thromboxane A2, radioimmunoassayed in venous blood as thromboxane B2, increased by 2452 ± 800 pg/mL. A second group of piglets was treated with dimethylthiourea (DMTU: 750 mg/kg), a putative oxygen radical scavenger. In these animals, GBS increased pulmonary arterial pressure by only 7 ± 1 torr and reduced arterial PO2by a modest 10 ± 8 torr. Importantly, thromboxane B2content in venous blood failed to increase above control levels in DMTU-treated animals. The protective effects of DMTU in GBS-treated piglets could not be ascribed to inhibition of cyclooxygenase or thromboxane synthase because the oxygen radical scavenger failed to attenuate increases in pulmonary arterial pressure and venous thromboxane B2content or reductions in arterial PO2caused by i.v. infusions of arachidonic acid. DMTU also did not ameliorate pulmonary hypertension evoked by the thromboxane mimetic U44069, thereby suggesting that the scavenger did not act as an end-organ antagonist of thromboxane receptors. These observations suggest that GBS promotes accumulation of thromboxane A2and attendant pulmonary hypertension through an oxygen radical-dependent mechanism.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Selected metabolic, hematologic, and immunologic functions were evaluated in 3- to 6-mo-old Finish infants who received whole-cell pertussis-component diphtheria and tetanus toxoids and pertussis vaccine, adsorbed (DTP) vaccine, and in 4- to 6-y-old Los Angeles children who received either a licensed DTP vaccine or an acellular pertussis component DTP vaccine. One d after immunization, there was an increase in total leukocytes and neutrophils and a decrease in lymphocytes in all vaccinees. In 4- to 6-y-old children the leukocytosis and neutrophilia were greater in recipients who received the standard DTP vaccine than in vaccinees who received an acellular pertussis component DTP vaccine. In infants there was an increase in the mean plasma insulin concentration but no change in the glucose concentration 24 h after immunization; no increase in the mean plasma insulin was noted in the 4- to 6-y-old children. Three 4- to 6-y-old vaccinees had higher circulating immune complex concentrations after immunization and two of these children had high clinical reaction scores. The etiology of adverse reactions after DTP immunization is multifactorial. In contrast with findings in animals, our findings do not demonstrate a clinically significant effect due to lymphocytosis-promoting factor on glucose metabolism in vaccinated children. Neutrophilia in vaccinees is probably due to endotoxin, and some reactions may be due to circulating immune complexes.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Sera from 3 of 30 adults vaccinated withHaemophilus influenzaetype b polysaccharide vaccine (Hib PS) had poor complement-mediated bactericidal activity despite the presence of anti-Hib PS antibody concentrations of 8.6 to 20.5 µg/niL. These “nonkiller” antibodies killed <0.4 log cfu/mL compared to >3 logs with all but one of the other sera. To investigate the basis of this poor functional activity, we characterized in detail the IgG antibodies to Hib PS present in two of the nonkiller sera, and compared the results with two of the “killer” sera. The latter were selected based on comparable levels of total antibody to Hib PS. No consistent differences were found between the relative proportions of IgG or IgA antibody to total anti-Hib PS antibody, or the respective ratios of IgG1 to IgG2 antibody in the nonkiller and killer sera. IgG fractions, and IgG affinity purified antibody to Hib PS were prepared. When tested at 2 µg/mL of antibody, the IgG fractions from the two nonkiller sera had much lower bactericidal activity than the corresponding fractions from the killer sera (3 logs less killing), and the former also had lower complement-mediated opsonic activity (20 and 13% uptake by human PMN compared to 62 and 93%). These data show the striking variability in the functional activity of vaccine-induced antibody to Hib PS. Antibody functional activity is likely to be affected by a number of factors but one important variable appears to be avidity since the IgG anti-Hib PS antibody from the two nonkiller sera had 2- to 5-fold lower avidity than the IgG antibody from the two killer sera. Therefore, measurement of antibody avidity in studies of Hib vaccine immunogenicity would be informative

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Total IgG concentrations, IgG antibody concentrations to pooledEscherichia coliantigens, and IgG anti-E. coliantibody avidity were measured in cord and maternal serum samples collected from 52 mother-infant pairs after premature delivery (mean gestational age 28 wk, range 23-33 wk). The mean IgG anti-E. coliantibody concentration in cord serum (1.86 relative units/mL) was markedly lower than in maternal serum (5.42 relative units/mL) at this gestation (p<0.0001). Cord serum IgG anti-E. coliantibody concentrations correlated closely with maternal IgG anti-E. coliconcentrations when controlled for the effect of gestational age (partial correlation coefficient 0.89;p<0.001) but only weakly with gestational age when controlled for maternal IgG antibody concentrations (partial correlation coefficient 0.23;p=0.06). The mean ratio of cord to maternal IgG anti-E. coliantibody concentrations was considerably lower than the mean ratio for total IgG concentrations (0.34 versus 0.72;p<0.001). The mean avidity of IgG antibody for the pooledE. coliantigens was significantly greater in cord serum than in maternal serum (2.45versus1.99M;p<0.0001). There was a close correlation between cord and maternal antibody avidity (r=0.70;p<0.001), but cord IgG antibody avidity did not correlate with gestational age (r=-0.07;p=0.61), nor with cord IgG anti-E. coliantibody concentrations (r=0.10;p=0.50). Heat stable serum opsonic activity for the pooledE. coliantigens per unit of IgG antibody, measured by augmentation of normal neutrophil iodination responses, was 2-fold greater in cord serum than maternal serum for the 20 serum pairs tested. Heat stable opsonic activity per unit of IgG antibody correlated closely with IgG antibody avidity in cord and maternal sera (r=0.96 and 0.94, respectively). These findings suggest that there is selective transplacental transport of high avidity antibody with enhanced opsonic activity for these antigens early in the 3rd trimester of pregnancy.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

At birth, pulmonary vascular resistance decreases dramatically, allowing pulmonary blood flow to increase and oxygen exchange to occur in the lungs. To determine the extent to which ventilation of the fetus's lungs, oxygenation of the lungs, and umbilical cord occlusion can account for this decrease in resistance, we studied 16 chronically instrumented, near-term sheep fetuses inutero. We performed the experiment in a sequential fashion: we first studied the effects of ventilation alone (without oxygenation) on pulmonary vascular resistance and blood flow, and then determined the additive effects of oxygenation and cord occlusion. We calculated pulmonary vascular resistance from measurements of vascular pressures and measurements of pulmonary blood flow obtained by injecting radionuclide-labeled microspheres. We found that ventilation alone caused a large but variable increase in pulmonary blood flow, to 401% of control, no change in pulmonary arterial pressure, and a doubling of left atrial pressure. Thus, pulmonary vascular resistance fell dramatically, to 34% of control. Oxygenation caused a modest further increase in pulmonary blood flow and a decrease in mean pulmonary arterial pressure, so resistance fell to 10% of control. Umbilical cord occlusion caused no further changes in pressure, flow, or resistance. Unexpectedly, the fetuses' pulmonary blood flow responses to ventilation fell into two groups: the mean increase was maximal in eight of the 16 fetuses but was only 20% of the cumulative increase in the other eight. We found no differences between the two groups of fetuses to explain their different responses. We conclude that ventilation and oxygenation together can account for the decrease in pulmonary vascular resistance to levels that occur at birth. Moreover, ventilation alone can account for most of this decrease.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID