Modeling of autonomic control in sleep-disordered breathing

There is ample evidence to support the notion that chronic exposure to repetitive episodes of interrupted breathing during sleep can lead to systemic hypertension, heart failure, myocardial infarction and stroke. Recent studies have suggested that abnormal autonomic control may be the common factor linking sleep-disordered breathing (SDB) to these cardiovascular diseases. We have developed a closed-loop minimal model that enables the delineation of the major physiological mechanisms responsible for changes in autonomic system function in SDB, and also forms the basis for a noninvasive technique that enables the early detection of cardiovascular control abnormalities. The model is "minimal" in the sense that all its parameters can be estimated through analysis of the data measured noninvasively from a single experimental procedure. Parameter estimation is enhanced by broadening the frequency content of the subject's ventilatory pattern, either through voluntary control of breathing or involuntary control using ventilator assistance. Although the original form of the model is linear and time-invariant, extensions of the model include the incorporation of nonlinear dynamics in the autonomic control of heart rate, and allowing the transfer functions of the model components to assume time-varying characteristics. The various versions of the model have been applied to different populations of subjects with SDB under different conditions (e.g. supine wakefulness, orthostatic stress, sleep). Our cumulative findings suggest that the minimal model approach provides a more sensitive means of detecting abnormalities in autonomic cardiovascular control in SDB, compared to univariate analysis of heart rate variability or blood pressure variability.