Alcohol dependence compromises vagal output measured before sleep onset, which correlates with loss of delta sleep and with morning reports of sleep impairments. Testing of interventions that target sympathovagal balance might identify new strategies for partial amelioration of the sleep disturbances and impairments in daytime functioning observed in persons with alcohol dependence.

Cocaine dependence is associated with an increased risk of infectious diseases. The innate immune system triggers effector pathways to combat microbial pathogens through expression of tumor necrosis factor-␣ (TNF-␣) and interleukin-6 (IL-6). It is not known whether cocaine alters the capacity of monocytes to respond to a bacterial challenge in humans. In cocaine-dependent volunteers and control subjects, we analyzed monocyte TNF-␣ and IL-6 expression at rest and in response to the bacterial ligand, lipopolysaccharide (LPS), over a 24-h period. In addition, the in vivo effects of cocaine (40 mg) versus placebo on monocyte expression of TNF-␣ and IL-6 were profiled over 48 h. Cocaine-dependent volunteers showed a decrease in the capacity of monocytes to express TNF-␣ and IL-6 compared with control subjects. Moreover, acute infusion of cocaine induced a further decline in the responsiveness of monocytes to LPS, which persisted after cocaine had cleared from the blood. Heart rate variability analyses showed that increases of sympathetic activity along with vagal withdrawal were associated with decreases in monocyte expression of TNF-␣. Cocaine alters autonomic activity and induces protracted decreases in innate immune mechanisms. Targeting sympathovagal balance might represent a novel strategy for partial amelioration of impairments of innate immunity in cocaine dependence.

We performed time-varying spectral analyses of heart rate variability (HRV) and blood pressure variability (BPV) recorded from 16 normal humans during acoustically induced arousals from sleep. Time-varying autoregressive modeling was employed to estimate the time courses of high-frequency HRV power, low-frequency HRV power, the ratio between low-frequency and high-frequency HRV power, and low-frequency power of systolic BPV. To delineate the influence of respiration on HRV, we also computed respiratory airflow high-frequency power, the modified ratio of low-frequency to high-frequency HRV power, and the average transfer gain between respiration and heart rate. During cortical arousal, muscle sympathetic nerve activity and heart rate increased and returned rapidly to baseline, but systolic blood pressure, the ratio between low-frequency and high-frequency HRV power, low-frequency HRV power, the modified ratio of low-frequency to high-frequency HRV power, and low-frequency power of systolic BPV displayed increases that remained above baseline up to 40 s after arousal. High-frequency HRV power and airflow high-frequency power showed concommitant decreases to levels below baseline, whereas the average transfer gain between respiration and heart rate remained unchanged. These findings suggest that 1) arousal-induced changes in parasympathetic activity are strongly coupled to respiratory pattern and 2) the sympathoexcitatory cardiovascular effects of arousal are relatively long lasting and may accumulate if repetitive arousals occur in close succession.

Background-In alcohol dependence, markers of inflammation are associated with increases in rapid eye movement (REM) sleep, which is thought to be a prognostic indicator of alcohol relapse. This study was undertaken to test whether blockade of biologically active tumor necrosis factor-α (TNF-α) normalizes REM sleep in alcohol-dependent adults.

Respiration, R-R interval, blood pressure, and other polysomnographic variables were recorded in eight normal subjects and nine patients with untreated obstructive sleep apnea syndrome in wakefulness and sleep. To increase respiratory and cardiovascular variability, a computer-controlled ventilator delivered randomly modulated inspiratory pressures that were superimposed on a baseline continuous positive airway pressure. A mathematical model allowed heart rate variability to be partitioned into a component mediated by respiratory-cardiac coupling and one mediated by the baroreflexes. Respiratory-cardiac coupling gain was lower in patients versus normal subjects (36.9 +/- 3.3 versus 66.1 +/- 5.6 milliseconds L-1, p < 0.03). Baroreflex gain in patients was also depressed relative to normal subjects (2.3 +/- 0.4 versus 4.9 +/- 0.7 milliseconds mm Hg-1; p < 0.02). Baroreflex gain increased two- to threefold from wakefulness to sleep in normal subjects, but was relatively unaffected by state change in patients. Along with results derived from spectral analysis of cardiovascular variability, these findings confirm previous reports that obstructive sleep apnea syndrome is associated with reduced parasympathetic and elevated sympathetic activity. The model-based approach provides a more precise characterization of heart rate variability that can be employed in conjunction with spectral analysis for the noninvasive detection and assessment of autonomic cardiovascular abnormality in obstructive sleep apnea syndrome.