POSTNATAL MATURATION OF CARDIOVASCULAR REGULATORY SYSTEM

Suny Downstate Medical Center, Brooklyn NY

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Abstract

DESCRIPTION (Verbatim from the application): The overall goal of this proposal is to provide physiological and anatomical indices of maturation within neural networks involved in cardiorespiratory (CV-RESP) regulation. We shall focus on brainstem circuit neurons that mediate the CV-RESP responses to hypercapnic stress because: (a) this circuit plays an essential role in the maintenance of blood/gas homeostasis and (b) evidence suggesting that maladaptive responses to hypercapnic stimulation may be involved in the pathogenesis of Sudden Infant Death Syndrome (SIDS).The swine model of early development will be used to test the hypothesis that CV-RESP responses to prolonged hypercapnia are: (a) age-related, (b) modulated by peripheral afferent inputs, and (c) mediated by central a2-adrenoceptors. We also hypothesize that the network response to hypercapnia involves area postrema, nucleus tractus solitarii, and their synaptic targets within sympathetic (SYMP) control regions of the lateral medullary reticular formation. We shall test our hypothesis that catecholaminergic cell areas of the piglet medulla, previously shown to be activated by (a) CO2 and (b) hypotension, play crucial roles in the coordinated response. Of special significance are a subset of epinephrinergic neurons located in the SYMP premotor region of the rostral ventrolateral medulla. The effects of prolonged hypercapnia on SYMP outflow from at least two different segmental levels will be recorded, simultaneously with phrenic (PHR) activity. lEG expression will be quantitated with respect to age and brain stem sites. Age-related alterations in physiologic and neqronal responses to hypercapnia will be assessed following blockade of central alpha-2 receptors. Peripheral denervation will determine the importance of peripheral afferent inputs versus central effects ofhypercapnia at different ages. The correlation between lEG expression and SYMP-PHR outflows should reveal whether age-related changes in CV-RESP brain circuits (suggesting periods of vulnerability), are also observed in SYMP-PHR outflows; thus explaining the absence of a linear pattern of maturation of CV responses with stress. These studies should identify apparent dissociation between level of lEG expression (neuronal activation), SYMP coherence (regulatory outflow) and CV-RESP responses to stress (critical developmental period). The results should help in our understanding of the most vulnerable period in the life of the child and the pathogenesis ('window of opportunity') of SIDS.