Sudden infant Death Syndrome (SIDS) remains the most frequent cause of death in young infants. While the etiology of SIDS remains largely unknown an abnormality of cardio-respiratory control ('autonomic dysfunction') has been suggested. While the autonomic nervous system is known to be immature at birth there are little data regarding normal postnatal maturation of autonomic regulation of cardiac function and virtually none regarding external factors which may perturb this developmental process. Utilizing a newborn canine model, we plan to first characterize the normal time course and sequence of postnatal maturation of cardiac autonomic effector responses. This will be accomplished by tracking over the first 3 months of life well defined indices of parasympathetic and sympathetic function that have been reported to be altered at birth. These indices include: 1. The magnitude and time course of changes in heart rate, AV nodal conduction and atrial refractoriness in response to tonic (3-20 Hz) vagal stimulation. 2. The amplitude and configuration of phase response curves (PRCs) for heart rate and AV nodal conduction generated in response to brief, critically timed vagal stimuli. 3. The magnitude and direction of change in vagal responses as a function of concomitant electrical sympathetic stimulation (sympathetic-parasympathetic interactions). 4. The chronotropic response of the sinus node and AV junctional pacemaker to alpha and beta-adrenergic agonists. 5. The effects of the autonomic co- transmitters vasoactive intestinal peptide on heart rate and neuropeptide Y on evoked parasympathetic responses. After defining normal maturation, studies will then be performed to elucidate how low birth weight, exposure to hypoxia, hypothermia, and elevated levels of corticosteroids (a neurohumoral correlate of stress) may modify the expression of autonomic effector responses. These studies are expected to yield insight into normal and abnormal developmental processes that are relevant to an understanding of Sudden Infant Death Syndrome.
