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Query: UMLS:C0020440 (hypercapnia)
 7,939 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the entry of 3H-bilirubin and 125I-albumin into brain regions in young rats during short-term (1 h) hyperbilirubinemia. Bilirubin enters the brain both under control, displacer (sulfisoxazole 50 mg/kg), hypercarbic (PCO2 18-21 kPa; pH approximately 6.9), and hyperosmolar (serum osmolality approximately 400 mosm/l) conditions. No significant differences in bilirubin uptake were found between brain regions. Thus preferential staining of basal ganglia ('kernicterus') may not be a phenomenon related to uptake. Albumin does not cross the blood-brain barrier under control or displacer conditions, but does enter the brain to some extent in hypercarbia, and to a greater extent in hyperosmolality. During control and displacer conditions, only unbound bilirubin appears to enter the brain. In hypercarbia bilirubin enters primarily in the unbound form, but some is also albumin-bound. In hyperosmolality a significant fraction of the bilirubin entering the brain is albumin-bound.
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PMID:Effects of sulfisoxazole, hypercarbia, and hyperosmolality on entry of bilirubin and albumin into brain regions in young rats. 250 67

In recent studies of bilirubin encephalopathy, in situ flushing of the cerebral vessels has been used to clear blood from the brain. The effectiveness of such procedures has not been adequately documented. Herein young, male Sprague-Dawley rats were given about 750 KBq of 51Cr-labelled rat erythrocytes 3 min prior to sacrifice. There were four experimental groups: control, displacer (sulfisoxazole), hyperosmolality, and hypercarbia. Half of the rats in each group had the brain vasculature flushed in situ, while the remaining rat brains were not flushed. The brains were dissected into seven regions, and the radioactivity in the tissues was compared to that of blood drawn from the rats immediately before death. Significant amounts of blood (22-42%) remained after in situ flushing. Retention was significantly higher in the hyperosmolar animals, and significantly lower in the hypercarbic animals as compared to controls. Interregional differences in blood volumes per gram wet weight were significant without, but not with flushing. Similar observations were made using 125I-IgM as a marker for the plasma compartment. In studies of brain uptake of substances with high plasma concentrations, substance remaining within the cerebral vessels may contribute significantly to the apparent brain uptake values.
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PMID:Cerebral blood volumes in young rats with and without in situ saline flushing of cerebral vasculature. Implications for in vivo studies of brain substance uptake. 275 81

Despite intensive investigation it remains uncertain how bilirubin enters the brain and how it exerts a toxic effect on neurones. Studies of induced hyperbilirubinemia in animal models in vivo have failed to reproduce bilirubin encephalopathy without additional factors such as hypoxia, asphyxia, hypercapnia, and disruption of the blood-brain barrier. The aim of this study was to investigate, using 31P NMRS, whether hyperbilirubinemia alone or in association with hyperosmolar opening of the blood-brain barrier caused any disturbance of cerebral energy metabolism in vivo. Spectra were acquired using a surface coil positioned over the right cerebral hemisphere of anaesthetized adult rats placed in the bore of a 1.9 Tesla magnet. Hyperbilirubinemia alone at a maximum mean serum concentration of 1063 +/- 175 mumol/L (mean +/- SD, n = 7) caused no apparent disruption in brain energy metabolism. However, in combination with hyperosmolar blood-brain barrier opening a serum bilirubin concentration of 483 +/- 52 mumol/L (mean +/- SD, n = 9) was associated with a reduction in PCr/(PCr + Pi) ratio from 0.68 +/- 0.06 to 0.44 +/- 0.14 (mean +/- SD, p less than 0.001). A significant correlation was demonstrated between cerebral hemisphere bilirubin content and the reduction in PCr/(PCr + Pi) (r = 0.84, n = 9, p less than 0.01). These results demonstrate in vivo a disruptive effect of bilirubin on cerebral energy metabolism in the presence of an open BBB. This mode of entry and mechanism of toxicity may be factors in the pathophysiology of bilirubin encephalopathy in the newborn infant.
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PMID:The effects of bilirubin on brain energy metabolism during hyperosmolar opening of the blood-brain barrier: an in vivo study using 31P nuclear magnetic resonance spectroscopy. 279 49

The aim of this study was to investigate (i) whether bilirubin encephalopathy with lasting sequelae could be created in a rat model, and (ii) putative differences in brain toxicity between bound and unbound bilirubin. Hyperbilirubinemia was produced by infusing bilirubin 20 mg/kg/h during 3 h into 6-week-old male Sprague-Dawley rats. In addition to the hyperbilirubinemia, different groups were created by exposing the rats to hyperosmolality, hypercarbia, and sulfisoxazole. Three weeks after the infusion the rats were studied in an open-field apparatus during 10 daily sessions of 15 min duration. A data collection program was used to study the following measures of activity: crossings in cage, peeks, rearing, latency to enter field, crossings in middle and in outer field, and time outside cage. The data were subjected to multivariate analyses of variance (MANOVA). Generally, the level of activity was higher in the bilirubin-treated rats as compared to the control animals. The difference in activity between bilirubin-treated and control rats changed systematically both between and within sessions. The data show that both unbound and albumin-bound bilirubin are neurotoxic, but they indicate a more pronounced effect of unbound bilirubin. The sequelae of bilirubin brain toxicity appear to include changes in stimulus processing. This is compatible with findings from neuropsychological tests of children who have had significant neonatal hyperbilirubinemia.
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PMID:Open-field behavior of rats previously subjected to short-term hyperbilirubinemia with or without blood-brain barrier manipulations. 369 Mar 1

Since kernicteric lesions are usually found in the subcortical regions of the brain and these areas also receive the highest blood flow during asphyxia and hypercapnia, we hypothesized that increases in brain bilirubin deposition may be related to increases in brain blood flow. Fourteen piglets underwent a 3-h infusion of bilirubin to maintain total serum bilirubin at approximately 8 mg/dl, during which time blood gases, hemodynamic variables, and brain blood flow were determined. After sacrificing the animals, regional brain bilirubin content was determined. Ten piglets underwent the same protocol; in addition, hypercapnia was induced during the last hour of study (PaCO2 approximately 70 mm Hg). The regional brain blood flow and bilirubin deposition were significantly increased over control values (p less than 0.05) following hypercapnia in the subcortical region and significantly so in the midbrain and cerebellum. In separate groups of control (n = 6) and hypercapnia (n = 6) piglets, 125I-labeled albumin was infused and demonstrated that hypercapnia was not associated with increased regional brain albumin content. We conclude that hypercapnia-induced augmentation in regional brain blood flow is associated with increased deposition brain blood flow is associated with increased deposition of unbound bilirubin. Although the causal relationship between these two observations has not been firmly established, the findings deserve future investigation to clarify the role of brain blood flow, brain bilirubin deposition, and the production of kernicterus in high risk infants.
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PMID:The effects of brain blood flow on brain bilirubin deposition in newborn piglets. 404 Jun 28

In recent years kernicterus at autopsy has been observed in sick premature infants in the absence of markedly elevated levels of serum bilirubin. Potentiating factors have been suggested to explain kernicterus in such a setting. In order to establish which factors are associated with increased risk for kernicterus in these small babies, this retrospective matched control study was undertaken. Thirty-two infants with kernicterus at autopsy were matched for gestational age, birth weight, length of survival, and year of birth to 32 control infants without kernicterus. Multiple historical, clinical, and laboratory factors were compared, including therapy, sepsis, hypothermia, asphyxia as reflected by Apgar score, hematocrit, acidosis, hypercarbia, hypoxia, hypoglycemia, and hyperbilirubinemia. No statistically significant differences between the kernicteric and nonkernicteric infants were demonstrated for any of these factors, including peak total serum bilirubin levels. Multivariant analysis also failed to determine a group of factors associated with increased risk for kernicterus. It was not possible to separate those infants with and without kernicterus at autopsy on the basis of the clinical factors evaluated.
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PMID:Lack of identifiable risk factors for kernicterus. 743 34