A model of experimental neonatal hyperbilirubinemia in the rat has been developed using the vitamin K analogue Synkayvite. Synkayvite was administered to neonatal rats 24 hours after birth and bilirubin levels, hematocrit, hemoglobin, methemoglobin, and reduced glutathione were analyzed at predetermined time intervals over the first fourteen days of life. Synkayvite administration increased bilirubin levels more than twice control neonates within one-half hour of injection. This elevation in treated animals initially declined to bilirubin values one and one-half of controls, remained at this plateau approximately three days then declined to levels equal to controls and adult values 14 days following Synkayvite treatment. Synkayvite caused slight neonatal hemolysis reflected by no decrease in red blood cells, no hematocrit decrease and no hemoglobin increase. Control and treated neonates had elevated methemoglobin values and depressed reduced glutathione values. Untreated Sprague Dawley neonates 1 day to 14 days old were evaluated for the red cell parameters; hematocrit, hemoglobin, methemoglobin, reduced glutathione, methemoglobin reduction and glutathione reductase. High neonatal methemoglobin levels during the first 2 days of life decreased to adult levels by 14 days and low reduced glutathione values during the first 2 days increased to adult values by 14 days of age. Normal neonatal red cell ability to reduce methemoglobin increased as the rat's age increased from 1 day to 14 days. Glutathione reductase activity of red blood cells did not change from 1 day of age to 14 days of age and similar to values reported in human erythrocytes. The Synkayvite treated neonatal rat model does not precisely replicate human infant hyperbilirubinemia since bilirubin levels rise to 1.2 mg/dl, 8-16 times lower than in the human hyperbilirubinemic neonate (10-20 mg/dl). However, Synkayvite administered with other treatments that influence bilirubin formation, such as plasma protein binding, hepatic protein binding or glucuronide conjugation may result in a model which imitates hyperbilirubinemia in humans. A simple neonate rat jaundice model reflecting the human neonate condition would be useful for studies into the biological, physiological effects and the potential for detrimental effects on the neuropsychological development of infants with elevated bilirubin levels.
| Identifer | oai:union.ndltd.org:UMASS/oai:scholarworks.umass.edu:dissertations-7771 |
| Date | 01 January 1990 |
| Creators | Gilbert, Charles Edward |
| Publisher | ScholarWorks@UMass Amherst |
| Source Sets | University of Massachusetts, Amherst |
| Language | English |
| Detected Language | English |
| Type | text |
| Source | Doctoral Dissertations Available from Proquest |
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