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Nearly two decades ago, we evaluated ten patients with obstructive sleep apnea (OSA). We determined that alarming nocturnal oscillations in arterial pressure and sympathetic nerve activity (SNA) were caused by regulatory coupling and neural interactions among SNA, apnea, and ventilation. Patients with OSA exhibited high levels of SNA when awake, during normal ventilation, and during normoxia, which contributed to hypertension and organ damage. Additionally, we achieved a beneficial and potentially lifesaving reduction in SNA through the application of continuous positive airway pressure (CPAP), which remains a primary therapeutic approach for patients with OSA. With these results in hindsight, we herein discuss three concepts with functional and therapeutic relevance to the integrative neurobiology of autonomic cardiovascular control and to the mechanisms involved in excessive sympathoexcitation in OSA.
Neural reflex interactions determine optimal autonomic cardiovascular response
An integrated autonomic response to com- bined stress signals is essential for optimal adjustment. For example, in the cardiovas- cular system, circulatory responses are typi- cally mediated through activation of the sympathetic and parasympathetic branches of the autonomic system and serve to maintain blood flow and oxygen delivery to vital organs (1, 2).
The oxygen-conserving reflex. Responses to obstructive sleep apnea (OSA) are triggered by hypoxia and apnea. During hypoxia, chemoreceptor activation promotes hyper- ventilation to enhance oxygen delivery to blood, which is followed by sympathetical- ly mediated vasoconstriction to redistrib- ute oxygenated blood flow to vital organs (1, 2) and parasympathetically activated bradycardia to reduce myocardial oxygen demand (3). Within each respiratory cycle, the cardiovascular response is maximal during expiration and suppressed during inspiration (4); however, this inhibitory coupling of respiratory afferent nerves with the chemoreceptor-mediated excita- tion of both sympathetic and parasym- pathetic efferents is dysfunctional during apnea (1, 3). Apnea unbridles an intense cardiovascular response in order to main- tain oxygen delivery, reduce cardiac oxy- gen demand, and promote survival. This is an oxygen-conserving reflex, similar to the evolutionarily conserved diving reflex in seals and ducks, that occurs in humans during facial immersion and apnea (5-7). Unfortunately, this physiologic response to hypoxia becomes pathological when the enhanced sympathoexcitation is sustained over years, as is the case in OSA.
Baroreceptor-chemoreceptor interaction. Sev- eral sensory signals converge during stress, resulting in an integrated reflex response. We have reported several...