R. Juarez

A Nonlinear Model of Cardiac Autonomic Control in Obstructive Sleep Apnea Syndrome

Using the Volterra–Wiener approach, we employed a minimal model to quantitatively characterize the linear and nonlinear effects of respiration (RCC) and arterial blood pressure (ABR) on heart rate variability (HRV) in normal controls and subjects with moderate-to-severe obstructive sleep apnea syndrome (OSAS). Respiration, R–R interval (RRI), blood pressure (BP) and other polysomnographic variables were recorded in eight normal controls and nine OSAS subjects in wakefulness, Stage 2 and rapid eye-movement sleep. To increase respiratory and cardiovascular variability, a preprogrammed ventilator delivered randomly timed inspiratory pressures that were superimposed on a baseline continuous positive airway pressure. Except for lower resting RRI in OSAS subjects, summary statistical measures of RRI and BP and their variabilities were similar in controls and OSAS. In contrast, RCC and ABR gains were significantly lower in OSAS. Nonlinear ABR gain and the interaction between respiration and blood pressure in modulating RRI were substantially reduced in OSAS. ABR gain increased during sleep in controls but remained unchanged in OSAS. These findings suggest that normotensive OSAS subjects have impaired daytime parasympathetic and sympathetic function. Nonlinear minimal modeling of HRV provides a useful, insightful, and comprehensive approach for the detection and assessment of abnormal autonomic function in OSAS.

Autonomic Cardiovascular Control Following Transient Arousal From Sleep: A Time-Varying Closed-Loop Model

Recent studies suggest that exposure to repetitive episodes of hypoxia and transient arousal can lead to increased risk for cardiovascular disease in patients with obstructive sleep apnea syndrome (OSAS). To obtain an improved understanding of and to quantitatively characterize the autonomic effects of arousal from sleep, a time-varying closed-loop model was used to determine the interrelationships among respiration, heart rate and blood pressure in 8 normal adults. A recursive least squares algorithm was used in combination with the Laguerre expansion technique to estimate the time-varying impulse responses of the 4 model components. We found that during arousal: 1) respiratory-cardiac coupling gain increases in nonrapid-eye movement (NREM) but not in REM sleep; 2) in both NREM and REM sleep, baroreflex gain shows an initial increase, but this is followed by a more sustained decrease below pre-arousal baseline levels, allowing sympathetic tone to be elevated over a relatively long duration; 3) the gains of other model components show increases with arousal that are consistent with the increased sympathetic modulation of systemic vascular resistance and contractility of the heart. These findings establish a normative database against which further measurements of cardiovascular arousal responses in OSAS may be compared.

Time-varying analysis of autonomic control during arousal from sleep in obstructive sleep apnea syndrome

Patients with obstructive sleep apnea syndrome (OSAS) have elevated sympathetic drive and impaired parasympathetic cardiac control during wakefulness and sleep. Previous studies have demonstrated that sympathetic overactivity in OSAS can lead to impaired peripheral vasodilatory responses to hypoxia. The present study was conducted to determine whether the autonomic response to arousal from sleep is also altered in OSAS. In 8 OSAS and 8 normal controls, we performed time-varying spectral analyses of cardiovascular and respiratory variability following acoustically-induced arousal from sleep. In all subjects and in both REM and non-REM sleep, the arousal responses of the spectral parameters representing vagal heart-rate modulation were small or non-existent after accounting for the accompanying changes in respiration. In non-REM sleep, the OSAS subjects showed substantially attenuated cardiac sympathetic responses to arousal but the peripheral vascular response was preserved. In REM sleep, the sympathetic cardiovascular responses to arousal were similar in both subject groups, but these responses were much smaller than those exhibited by normals in non-REM sleep. Our results suggest that OSAS leads primarily to an impairment of the cardiac sympathoexcitatory reaction to arousal from non-REM sleep; however, the normal autonomic cardiovascular response to arousal in REM sleep appears to be preserved.

Effects of arousal from sleep on autonomic cardiovascular control in obstructive sleep apnea syndrome

To determine the importance of arousals from sleep on alterations of the cardiovascular control associated with obstructive sleep apnea syndrome (OSAS) we measured heart-rate, continuous blood pressure and respiration in 5 OSAS patients and 5 control subjects during test procedures performed in overnight sleep. The tests consisted of inducing arousal with acoustic stimuli randomly delivered when subjects were in a stable sleep stage. Time-varying systems identification by means of the Laguerre expansion technique allowed the tracking of arousal-induced changes in the impulse responses of the respiratory sinus arrhythmia (RSA) and baroreflex (ABR) components of the cardiovascular control model. In the control group, significant reductions in ABR gain were detected during arousal. These changes were not observed in the OSAS group. RSA gain increased in controls during arousal, but its time course in OSAS was found to be significantly different. The lack of ABR reaction to arousal in OSAS reflects an impaired baroreflex that results from chronic exposure to repeated apnea episodes usually accompanied by sleep disruption.

Closed-loop minimal model analysis of the cardiovascular response to transient arousal from sleep in healthy humans

In a previous work we reported discrepancies in the cardiovascular response to arousal from NREM sleep between OSAS patients and healthy controls. The long lasting cardiac sympathetic increase observed in normals was not present in the OSAS group, whereas the peripheral vasculature reaction was similar between the two groups. Analysis of REM arousal revealed that there was a similar temporary cardiac sympathetic impairment in the control group. In this work we have implemented a model-based time domain system identification method to assess the mechanisms involved in this reaction to arousal from both NREM and REM sleep in a group of healthy subjects. The use of time-varying techniques has enabled us to characterize the arousal reaction by analyzing the change in shape of the impulse responses of the system. The mechanisms regulating respiration and vascular effects on heart rate (respiratory sinus arrhythmia or RSA and arterial baroreflex or ABR, respectively) were the most affected by NREM arousal, likely as a result of the return of the wakefulness stimulus. The effect observed on the cardiac influence on the vasculature (circulatory dynamics, CID) was attributed to a change in the dominant mechanism prevailing in its dynamics.