Abstract â–¡ 74

The ability to rapidly adjust to changes in environmental, state, and/or metabolic conditions while maintaining tightly controlled homeostasis is one of the major adaptive mechanisms underlying survival in living creatures. Sophisticated systems have evolved to allow for preservation of such homeostasis. However, these systems may not be fully integrated or operational during the initial stages of postnatal life, thereby leading to the emergence of vulnerable states under certain circumstances. Examples of such situations include the onset of apnea and/or bradycardia during sleep. Sleep states exert major effects on moment-to-moment expression of breathing, cardiac rhythm and output, and autonomic control, as well as on evoked responses to specific challenges. The momentary changes are typically disproportionate to metabolic demands; thus, a portion of the variation associated with state reflects neural processes other than mechanisms essential for homeostasis, and, in some instances, may compromise vital needs. For example, transient blood pressure increase suppresses respiratory activity (preferentially in the upper airway musculature, and thus a particular danger for airway obstruction), slows breath-to-breath timing, and induces arousal, while lowering blood pressure stimulates ventilation. Conversely, respiratory efforts vary cardiac rate, with cardiac acceleration accompanying inspiration and deceleration associated with expiration. Both the pressor effects on breathing, and respiratory modulation of cardiac rate are accentuated by sleep. A large number of motor or vocalization events, central or obstructive apnea during sleep, or increased inspiratory or expiratory loading can initiate large blood pressure changes, which then can reflexively modify subsequent motor events. Hypoxia developing from inadequate ventilation initiates a substantial reorganization of metabolic rate and sympathetic outflow, with consequences to heart rate, blood pressure, and body temperature. Reaction to provocative challenges are superimposed on levels of background rate and variability which vary remarkably with age and state. The multiplicity of central systems whose function is to preserve homeostasis, and the elevated number of interdependencies occurring between functionally-related structures in the central network usually ensure proper activation of back-up defense systems and overall system stability during state transitions. However, perturbations can coincide with normally functioning transitional states, and can lead to disrupted responses or to generation of vulnerable states. The characteristics of such developmental changes are dictated at least in part, by environmental, metabolic, state conditions and overall neuronal activity of each network compartment, thereby creating infinite permutation possibilities in the overall network, i.e., individual and temporal variabilities. Thus, careful consideration of behavioral states and autonomic nervous system developmental stages must be incorporated in experimental or clinical settings to allow for improved understanding and interpretation of central cardiovascular and respiratory control mechanisms and their responses to particular stimuli.

Supported by NIH HD-01072, HD-22506, HD-22695, HL-22418, MCJ-229163, and the American Lung Association CI-002-N.