The majority of sudden infant death syndrome (SIDS) occurs between 2 and 4 months of age. In this age period several of the control systems regulating vital functions are still being developed and stabilized. Some of these control systems, such as control of breathing and sleep control are extremely complex and involve several organs. Asynchronous development of one or more parts of a control system may lead to failure, such as the inability to abort apnea. Failure to abort apnea will lead to progressive hypoxia and finally to cardiovascular collapse and death. This application proposes to utilize a chronic, unanesthetized lamb preparation as an animal model for SIDS. Laryngeal chemoreceptor reflex (LCR) stimulation will be used to induce reflex apnea. The animal model will allow us to test a wide variety of hypotheses in the proposed pathogenesis of SIDS involving factors modulating reflex apnea response, such as arousal from sleep, peripheral and central chemoreceptors, hypoxia, prematurity, bundling and the effects of maternal and passive smoking. The effect of these factors on reflex apnea will be assessed during wakefulness and sleep in chronically instrumented, unanesthetized premature and term newborn lambs as well as in older lambs. The response to LCR stimulation will be studied in carotid body denervated and in lambs with chemically inhibited peripheral and/or central chemoreceptors. The role of delayed and reversed postnatal reset of the carotid body oxygen sensitivity reflex apnea will be assessed. Our previous studies have shown that beta-adrenergic agonists reduce the LCR response and that alcohol enhances the LCR response in newborn lambs. Further, carotid body denervation (CBD) and lack of arousal during sleep increase the reflex apnea response. We propose to gain further knowledge about factors that interrupt apnea. A better understanding of these mechanisms could eventually lead to identification of potential SIDS victims and to the prevention of their demise.

Project Start
1986-12-01
Project End
1991-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203