Several studies have suggested that infants to succumb to sudden infant death syndrome (SIDS), have abnormalities in central cardiorespiratory control mechanisms. Pathologic data suggest these infants suffer from chronic hypoxemia. Clinically, these infants do not appear hypoxic prior to death. Presumably, the cardiorespiratory control abnormalities lead to hypoxic events, particularly during sleep. However, sleep studies have failed to adequately recognize those infants at risk. Alternatively, chronic intrauterine hypoxia may alter newborn ventilatory control mechanisms predisposing these infants to sudden death. An animal model of chronic intrauterine hypoxia (CIH) has been developed in the rabbit. Pregnant rabbit does are reared in 12% oxygen environment from 14-28 days gestation, the animals are then returned to room air and are permitted to litter in a normal fashion (31 days). Individual rabbit pups are removed from the litter at specified postnatal ages. Ventilation is measured in a pressure plethtysmograpy. Hypoxic and hypercapnic challenges are presented to the animals and their responses recorded. At the completion of the ventilatory studies, the animal is euthanized and the brains are removed for study. Alternatively, intermittent fetal hypoxemia is induced pharmacologically by injections of cocaine hydrochloride. Preliminary studies in both models have shown significant alterations in minute ventilation between control and experimental animals which are less than 48 hours of age. Also, dramatic neuropaatholoogic changes, neuronal eosinophilia, nuclear pyknosis and frank necrosis have been seen in the experimental groups. This proposal is intended to further characterize both the ventilatory and neuroptholgic changes. Peripheral chemoreceptor, neurotransmitter and cerebral blood flow studies will be performed to elucidate the underlying mechanisms responsible for these changes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08NS001303-01
Application #
3084198
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Project Start
1988-09-01
Project End
1993-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033