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. 1999 Mar 1;515(Pt 2):621–628. doi: 10.1111/j.1469-7793.1999.621ac.x

Arousal from sleep shortens sympathetic burst latency in humans

Ailiang Xie *, James B Skatrud *, Dominic S Puleo *, Barbara J Morgan †
PMCID: PMC2269153  PMID: 10050027

Abstract

  1. Bursts of sympathetic activity in muscle nerves are phase-locked to the cardiac cycle by the sinoaortic baroreflexes. Acoustic arousal from non-rapid eye movement (NREM) sleep reduces the normally invariant interval between the R-wave of the electrocardiogram (ECG) and the peak of the corresponding sympathetic burst; however, the effects of other forms of sleep disruption (i.e. spontaneous arousals and apnoea-induced arousals) on this temporal relationship are unknown.

  2. We simultaneously recorded muscle sympathetic nerve activity in the peroneal nerve (intraneural electrodes) and the ECG (surface electrodes) in seven healthy humans and three patients with sleep apnoea syndrome during NREM sleep.

  3. In seven subjects, burst latencies were shortened subsequent to spontaneous K complexes (1.297 ± 0.024 s, mean ± s.e.m.) and spontaneous arousals (1.268 ± 0.044 s) compared with latencies during periods of stable NREM sleep (1.369 ± 0.023 s). In six subjects who demonstrated spontaneous apnoeas during sleep, apnoea per se did not alter burst latency relative to sleep with stable electroencephalogram (EEG) and breathing (1.313 ± 0.038 vs. 1.342 ± 0.026 s); however, following apnoea-induced EEG perturbations, burst latencies were reduced (1.214 ± 0.034 s).

  4. Arousal-induced reduction in sympathetic burst latency may reflect a temporary diminution of baroreflex buffering of sympathetic outflow. If so, the magnitude of arterial pressure perturbations during sleep (e.g. those caused by sleep disordered breathing and periodic leg movements) may be augmented by arousal.

Bursts of sympathetic vasoconstrictor activity in muscle nerves are tightly linked to the cardiac cycle. Because of the influence of the sinoaortic baroreflexes, muscle sympathetic bursts occur predominantly during diastole when arterial pressure is transiently reduced, and they are interrupted or delayed during systole when arterial pressure rises (Delius et al. 1972; Fagius et al. 1985). As a result, there is a reproducible time delay, or latency, from the R-wave of the electrocardiogram to the peak of the corresponding sympathetic burst on the mean voltage neurogram (Delius et al. 1972; Fagius & Wallin, 1980). Under resting conditions, the mean burst latency for muscle vasoconstrictor impulses is quite constant for a given person at a given recording site, irrespective of fluctuations in heart rate (Fagius & Wallin, 1980).

We have previously demonstrated that auditory arousal from sleep reduces sympathetic burst latency (Morgan et al. 1996). Other investigators have observed shortening of this latency during the Valsalva manoeuvre, simulated diving, and slow deep breathing during wakefulness (Fagius et al. 1987). Although the physiological significance of burst latency shortening is unknown, it may reflect an alteration in baroreflex function that would result in weaker or shorter-lived systolic inhibition of sympathetic outflow. The purpose of this study was to determine whether shortening of sympathetic burst latency occurs with spontaneous and apnoea-induced arousals from sleep. Accordingly, in healthy human subjects and patients with sleep apnoea syndrome, we measured burst latency during stable non-rapid eye movement (NREM) sleep and during spontaneous arousals and apnoea-induced arousals from NREM sleep.

METHODS

Subjects

Seven healthy male subjects (age 38 ± 10 years (mean ±s.d.); range 29-58 years) and three male patients with sleep apnoea syndrome (age 45 ± 18 years; range 28-64 years) served as subjects. The healthy subjects were free from cardiovascular, pulmonary and neurological disease, as evaluated by history and physical examination. However, three of the healthy subjects demonstrated a small number of apnoeas (means of 3, 5 and 6 apnoeas per hour of sleep) during the experimental study, which we presume occurred because subjects were required to maintain the supine position during sleep. Sleep apnoea syndrome was confirmed in the three patients by in-laboratory overnight polysomnography (37, 46 and 134 apnoeas per hour of sleep, respectively) and symptoms of habitual snoring, fatigue and daytime sleepiness. Written, informed consent was obtained from all subjects, and the experimental protocol was approved by the Human Subjects Committees at the University of Wisconsin Center for Health Sciences and the Middleton Memorial Veterans Hospital.

General procedures

A single night study was performed with subjects lying supine in a quiet, darkened laboratory between the hours of 23.00 and 03.30 h. Subjects were asked to sleep deprive themselves by obtaining no more than 4 h of sleep on the previous night. The electroencephalogram (EEG) (C4/A1 and O1/A2) and submental electromyogram (EMG) were recorded with surface electrodes to identify sleep stage. The electrocardiogram (ECG) was recorded via surface electrodes placed on the chest. Arterial pressure was monitored continuously by finger-pulse photoplethysmograph (Finapres; Ohmeda, Englewood, CO, USA). Tidal volume was measured with an inductance plethysmograph (Respitrace; Ambulatory Monitoring, Ardsley, NY, USA) that was calibrated against a spirometer using the isovolume manoeuvre technique. Arterial oxygen saturation was measured at the earlobe with a pulse oximeter (Biox 3740; Ohmeda, Madison, WI, USA). All variables were recorded continuously on an 8-channel polygraph (Model 7D; Grass Instruments, Quincy, MA, USA) at a paper speed of 10 mm s−1 and on videotape for subsequent analog-to-digital conversion and computer analysis.

Muscle sympathetic nerve recording

Muscle sympathetic nerve activity was recorded from the peroneal nerve with intraneural microelectrodes using the technique of Vallbo et al. (1979). The neural signals were passed to a differential preamplifier, an amplifier and an integrator (time constant, 100 ms; total gain, 100 000). Placement of the recording electrode within a muscle nerve fascicle was confirmed by: (1) the presence of muscle twitches, not paresthesias, in response to electrical stimulation, (2) the pulse synchronous nature of the nerve activity, (3) the appearance of afferent activity in response to tapping or stretching of muscle, but not gentle stroking of skin, in the appropriate receptive field, and (4) the absence of neural activation in response to arousal stimuli during wakefulness. The filtered and mean voltage neurograms were recorded on the polygraph and on videotape along with the other variables mentioned above. The analog signals of the mean voltage neurogram were then converted to digital form (sampling frequency, 100 Hz) and fed into a computer.

Data analysis

Scoring of sleep stages, K complexes, arousals and sleep apnoeas

Sleep stages were scored according to standard criteria (Rechtschaffen & Kales, 1968). K complexes were defined as sharp negative waves (> 10 μV in amplitude) on the EEG tracing, followed by slower positive components, with the total duration of the complexes exceeding 0.5 s. These EEG events are thought to represent aborted arousals (Johnson & Karpan, 1968). Arousals were defined as abrupt desynchronizations (increases in frequency and voltage) of the EEG lasting 3-15 s, with or without concurrent increases in EMG activity (American Sleep Disorders Association, 1992). K complexes and arousals that occurred without preceding respiratory perturbations were considered spontaneous events. Sleep apnoea was identified by the absence of a tidal volume excursion for at least 10 s. Stable NREM sleep was defined as periods of sleep, at least 2 min in duration, during which there were no changes in sleep stage and no respiratory perturbations.

Identification of sympathetic bursts and measurement of burst latency and morphology

Sympathetic bursts were identified from the mean voltage neurogram using a computer program with a sampling rate of 126 Hz (Birkett et al. 1992). Artifacts caused by unintentional leg movements and static electricity discharge were eliminated by manual editing of the nerve recording. Sympathetic burst latency was measured from the peak of the burst to the appropriate R-wave of the ECG (Fagius & Wallin, 1980). In the range of heart rates observed in this study (52-86 beats min−1), the appropriate R-wave was the one that preceded the burst by one complete cardiac cycle (Fig. 1). This selection method was based on the time required for efferent conduction of sympathetic action potentials from the brainstem to the peroneal nerve recording site (0.9-1.0 s in subjects of average height) (Fagius & Wallin, 1980). Selection of the R-wave immediately preceding the burst would not be appropriate because this method would not allow for sufficient time for nerve conduction to the peripheral recording site. Measurement of burst latency was done via manual positioning of cursors on the computer screen and a custom-written analysis program that allowed a resolution of 0.016 s. Only those bursts with a clear peak were chosen for latency measurement; bursts with plateaus or double peaks were excluded from analysis. To measure burst onset interval and duration, we fitted tangent lines to the leading and trailing edges of each burst. The points of intersection of these tangent lines with the neurogram's baseline were marked as the burst onset and offset, respectively. If the leading or the trailing edge was composed of multiple segments with different slopes, the tangent line was fitted to the segment closest to the baseline. The burst onset interval was defined as the time from the appropriate R-wave of the ECG to the point of burst onset. The burst duration, calculated as the time from burst onset to burst offset, was measured in seconds. Burst amplitude, defined as the deviation of the peak of the burst from the neurogram's baseline, was measured in microvolts. The rate of rise for a burst was calculated as burst amplitude divided by the time from burst onset to the peak of the burst. Because burst amplitude, duration and rate of rise can be affected by the distance from the recording electrode to the nerve fibres under study, these burst morphology characteristics were subjected only to within-subject comparisons.

Figure 1. Polygraphic records of one subject showing the change in sympathetic burst latencies following a spontaneous K complex (A), spontaneous arousal (B) and an apnoea-induced arousal (C).

Figure 1

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Traces from top to bottom: electroencephalogram (EEG), electrocardiogram (ECG), integrated muscle sympathetic nerve activity (MSNA), and tidal volume (VT). * K complex-associated burst; ** spontaneous arousal-associated burst; *** apnoea arousal-associated burst. Numbers above the ECG traces indicate the sympathetic burst latency in seconds.

For each subject, latencies and onset intervals were measured for all sympathetic bursts that occurred during periods of stable NREM sleep, with the exception of bursts that occurred within three cardiac cycles after K complexes and sleep spindles. To evaluate the change in burst latencies and onset intervals associated with K complexes and spontaneous arousals, we examined all bursts that occurred within three cardiac cycles after the EEG perturbations. To evaluate the effects of apnoea and apnoea-induced arousal on burst latencies and onset intervals, we examined all bursts that occurred during apnoeas prior to EEG desynchronizations and all bursts that occurred in late apnoea or hyperpnoea within three cardiac cycles after the EEG change. In addition, to examine the change in burst latency within the course of an apnoea, we divided each apnoea into three equal intervals, termed early, mid and late apnoea. We then calculated mean latencies for bursts that occurred in each interval and in the post-apnoeic hyperpnoea period. Furthermore, we examined the effects of arousal on amplitude, rise rate and duration of sympathetic bursts by measuring these morphology characteristics in all bursts that took place within eight cardiac cycles before and three cardiac cycles after EEG evidence of spontaneous and apnoea-induced arousals.

Statistical analysis

To allow for equal weighting of each subject's data, the within-subject responses were averaged and then these averages were used to compute group mean values. Analysis of variance for repeated measures with Tukey's honestly significant difference post hoc analysis (Tukey, 1994) was used to compare latencies and onset intervals of bursts that followed spontaneous K complexes and arousals with those of bursts that occurred in stable NREM sleep in the seven healthy subjects. The three patients with sleep apnoea syndrome, because of their frequent respiratory perturbations, demonstrated too few spontaneous arousals to allow comparison. The same statistical test was used to compare latencies and onset intervals of bursts that occurred during apnoea and after apnoea-induced arousal with bursts that occurred in stable sleep in the three patients with sleep apnoea syndrome and the three otherwise healthy subjects who demonstrated apnoeas during our experiments. The morphological characteristics of bursts that occurred before and after spontaneous and apnoea-induced arousals were compared by Student's paired t tests. For all sympathetic bursts measured during sleep in each subject, Pearson product-moment coefficients of correlation were used to examine the relationships between: (1) burst latency and burst amplitude, (2) burst latency and length of the previous R-R interval, and (3) burst latency and systolic and diastolic pressures during the preceding cardiac cycle.

Probability values (P) of < 0.05 were considered statistically significant. Unless otherwise stated, data are presented as means ±s.e.m.

RESULTS

Sympathetic burst latency during stable NREM sleep

All ten subjects had at least 1 h of sleep, which was predominantly stage 1 and 2 (90% of the total sleep time). Only three subjects had short periods of stage 3-4 sleep, and none developed rapid eye movement sleep. Mean burst latency for the ten subjects during stable NREM sleep was 1.359 ± 0.023 s.

Effects of spontaneous arousal on sympathetic burst latency

Seven subjects demonstrated spontaneous arousals from sleep. In these subjects, 103 spontaneous K complexes and 31 spontaneous arousals were observed. Bursts occurring after spontaneous K complexes and spontaneous arousals had shortened latencies relative to those occurring in stable NREM sleep (1.297 ± 0.024 s for K complex and 1.268 ± 0.044 s for arousal vs. 1.369 ± 0.023 s for stable NREM sleep, P < 0.05) (Fig 1 and Fig 2). Parallel shortening of burst onset intervals was also observed (0.910 ± 0.028 s for K complex and 0.874 ± 0.045 s for arousal vs. 1.029 ± 0.29 s for stable NREM sleep, P < 0.05).

Figure 2. Comparison of sympathetic burst latency (A) and burst onset interval (B) in stable NREM sleep with those following 103 spontaneous K complexes and 31 spontaneous arousals in 7 healthy subjects.

Figure 2

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Values shown are means ±s.e.m.*P < 0.05vs. stable NREM sleep.

Effects of apnoea and apnoea-induced arousal on burst latency

All three patients with obstructive sleep apnoea syndrome and three subjects previously classified as ‘healthy’ demonstrated spontaneous apnoeas during sleep. In these subjects, burst frequencies, expressed as the percentage of cardiac cycles that contained bursts, were greater during mid and late apnoea (final two-thirds of apnoea duration) than during stable sleep (72 ± 9 vs. 51 ± 8%, P < 0.05). Likewise, burst amplitudes were greater during mid and late apnoea than during stable NREM sleep (1.6 ± 0.4 vs. 1.2 ± 0.3 μV, P < 0.05). The bursts that occurred during apnoea but prior to arousal had latencies that were comparable to those observed during sleep with stable breathing (1.313 ± 0.038 vs. 1.342 ± 0.026 s, P > 0.05) (Fig 1 and Fig 3). In contrast, the bursts that followed apnoea-induced arousals demonstrated shortened burst latency (1.214 ± 0.034 s). Burst onset intervals remained stable during apnoea, but were diminished after apnoea-induced arousal (0.944 ± 0.056 and 0.957 ± 0.057 vs. 0.811 ± 0.049 s, P < 0.05). In the absence of arousal, burst latencies remained stable as apnoeas progressed from the initial cessation of breathing through the post-apnoea hyperpnoeic periods (Fig. 4). Arousals, regardless of whether they occurred during late apnoea or post-apnoea hyperpnoea, were consistently associated with shortened burst latency. The effect of apnoea-induced arousal on burst latency was consistent across all subjects, in whom a wide range of apnoea frequencies was observed (3-86 apnoeas per hour of sleep).

Figure 3. Comparison of sympathetic burst latency (A) and burst onset interval (B) in stable NREM sleep with those that occurred during apnoea (prior to arousal) and following apnoea-induced arousal in 3 patients with sleep apnoea syndrome and 3 healthy subjects who demonstrated apnoeas.

Figure 3

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A total of 97 apnoeas were observed in these 6 subjects. Values shown are means ±s.e.m.*P < 0.05vs. stable NREM sleep.

Figure 4. Burst latencies of all sympathetic bursts that occurred in early, mid and late apnoea and during the post-apnoea hyperpnoea.

Figure 4

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A total of 97 apnoeas were observed in 6 subjects. In late apnoea and hyperpnoea, sympathetic bursts were separated based on whether concomitant EEG evidence of arousal was present (Inline graphic) or absent (□). Values shown are means ±s.e.m.*P < 0.05, arousals vs. all other categories.

Effects of spontaneous and apnoea-induced arousals on burst morphology

In comparison with the amplitudes of pre-arousal bursts, burst amplitudes were increased after spontaneous (3.33 ± 0.72 vs. 2.13 ± 0.44 μV, P < 0.05) and apnoea-induced arousals (2.24 ± 0.62 vs. 1.63 ± 0.41 μV, P < 0.05) (Fig. 5). Likewise, burst durations were longer after spontaneous (0.81 ± 0.06 vs. 0.66 ± 0.04 s, P < 0.05) and apnoea-induced arousals (0.73 ± 0.06 vs. 0.64 ± 0.06 s, P < 0.05). The rate of rise was steeper in post-arousal bursts; however, this effect was statistically significant only for apnoea-induced arousals (7.07 ± 1.70 vs. 5.58 ± 1.26 μV s−1, P < 0.05).

Figure 5. Burst morphology parameters before (Pre) and after (Post) spontaneous and apnoea-induced arousals in 6 subjects.

Figure 5

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The horizontal bars indicate group mean values. *P < 0.05, pre- vs. post-arousal.

Relationship of sympathetic burst latencies with burst amplitudes and R-R intervals

When all sympathetic bursts recorded during sleep were examined, we observed a weak negative correlation between burst latency and burst amplitude (r = -0.367± 0.059, with P < 0.05 in 8 of 10 subjects). No relationship was observed between burst latency and length of the preceding R-R interval (r = 0.184± 0.079, with P < 0.05 in 4 of 10 subjects). Burst latency was not correlated with systolic pressure (r = 0.043± 0.051, with P < 0.05 in 2 of 10 subjects), or diastolic pressure (r = 0.010± 0.074, with P < 0.05 in 2 of 10 subjects) during the preceding cardiac cycle.

DISCUSSION

The major finding of this study is that during NREM sleep, spontaneous arousals and apnoea-induced arousals consistently reduced sympathetic burst latency. The present work extends our previous observation of shortened burst latency following auditory arousals (Morgan et al. 1996) by showing that an abrupt change in sleep state, rather than acoustic stimulation, is likely to be the cause of this interruption in the pulse synchronous rhythm that normally characterizes sympathetic bursts targeted to skeletal muscle. The physiological significance of reduced burst latency is not known; however, reduction in latency may reflect arousal-induced attenuation of baroreflex control of sympathetic outflow that is analogous to the diminished baroreflex control of heart rate caused by mental arousal during wakefulness (Conway et al. 1983).

Critique of methods

A limitation of this study is that we recorded sympathetic discharge only in postganglionic neurones that innervate vascular structures in leg muscle. Although this discharge is representative of sympathetic outflow to skeletal muscle vascular beds elsewhere in the body (Rea & Wallin, 1989), our measurements do not allow inferences about the effects of arousal on sympathetic outflow to other organs and vascular beds.

The amplitude of sympathetic bursts recorded using the microneurographic technique depends on the proximity of the recording electrode to the nerve fibres under study. This distance varies among subjects and can be affected by involuntary leg movements during sleep. For this reason, we limited our analysis of burst amplitude to within-subject comparisons and we excluded from analysis data collection periods in which the neurogram was contaminated with motoneurone and mechanoreceptor afferent activity. Although the possibility of undetectable movement-related shifts in electrode position cannot be ruled out, such shifts would be expected to affect burst amplitude, rather than latency, and therefore cannot account for our very consistent observations of arousal-induced shortening of sympathetic burst latency. Furthermore, we observed shortening of burst latency following K complexes, as well as EEG desynchronizations. K complexes, which are cortical events thought to represent aborted arousal, are much less likely to be associated with concomitant EMG activity (Johnson & Karpan, 1968).

The microneurographic technique yields multiunit recordings of postganglionic action potentials. It is possible that the latencies of arousal-induced bursts appeared shorter, not because the bursts actually occurred early, but merely because of more synchronous arrival of action potentials at the recording site. We observed steeper rates of rise of the bursts that followed spontaneous and apnoea-induced arousals; therefore, enhanced synchronization cannot be ruled out as a cause of shortened burst latency. However, in addition to increased rate of rise, we also observed a decrease in burst onset interval, suggesting the possibility that arousal-induced bursts occurred earlier than expected.

Potential causes of arousal-induced shortening of sympathetic burst latency

In this and a previous study, we have demonstrated that abrupt transition from sleep towards wakefulness shortens sympathetic burst latency regardless of whether arousal occurs spontaneously, is evoked by apnoea, or is caused by an external stimulus (Morgan et al. 1996). Arousal-induced shortening of sympathetic burst latency is observed after both mild (K complexes) and more vigorous (EEG desynchronization) episodes of sleep disruption. In contrast, sleep by itself (i.e.the wakefulness to sleep transition) does not affect sympathetic burst latency (Hornyak et al. 1991; Takeuchi et al. 1994; Morgan et al. 1996). Results of the present study demonstrate that during apnoeas, asphyxia per se does not cause shortening of burst latency. These findings, taken together, indicate that the observed shortening of burst latency is an arousal-related rather than a sleep- or asphyxia-related phenomenon.

Several explanations for the observed arousal-induced shortening of sympathetic burst latency can be postulated. First, the baroreflex stimulation elicited by the previous systole could have been reduced in intensity. Our data argue against this possibility because we found no correlation between burst latency and the length of the preceding R-R interval or the level of systolic or diastolic pressure during the preceding cardiac cycle. Alternatively, the baroreflex stimulation elicited by the previous systole could have been less effective in causing sympathoinhibition because it was bypassed or over-ridden. We have no evidence to refute this possibility; therefore, arousal-induced attenuation of baroreflex function remains a potential explanation for our findings.

It is well known that during wakefulness arousal stimuli evoke increases in sympathetic activity in skin nerve fascicles, but not in muscle nerve fascicles (Vallbo et al. 1979). The current concept is that baroreflex inhibition prevents arousal-induced increases in muscle sympathetic nerve activity, whereas there is no concomitant inhibition of skin sympathetic nerve activity, a neural output not subject to baroreflex regulation. Evidence to support this concept comes from experiments in which arousal stimuli presented during wakefulness caused parallel activation of muscle and skin sympathetic nerve activity under conditions of transient baroreceptor deafferentation (Fagius et al. 1985). We reasoned that the shortened burst latency observed in our subjects may have occurred because arousal from sleep altered baroreflex control of sympathetic outflow. This explanation is consistent with the previous finding that baroreflex control of heart rate is relatively less sensitive in situations where mental attentiveness, or arousal, is high (i.e. reading and mental arithmetic) and more sensitive in situations where arousal is low (i.e. drowsiness and sleep) (Conway et al. 1983).

Correlative data obtained using spike-triggered averaging indicate that sympathetic outflow originates from neurones located in the medulla (Barman & Gebber, 1983; Gebber & Barman, 1985). These neurones are thought to be part of a brainstem oscillator, the output of which is entrained to the cardiac cycle by intermittent inhibitory input from arterial baroreceptors via neurones located in the nucleus of the solitary tract (Gebber, 1980; Ross et al. 1985; Jeske et al. 1993). In our subjects, arousal from sleep interrupted the normal cardiac rhythm of sympathetic outflow. This finding may indicate that arousal triggers bursts of sympathetic activity, originating from suprabulbar regions, that are not subject to baroreflex buffering in the medulla, or that arousal over-rides baroreceptor-mediated inhibition of medullary ‘vasomotor’ neurones, thereby allowing early evolution of sympathetic bursts. Although we cannot support or refute either of these mechanisms on the basis of our data, there is experimental evidence to support both possibilities. Anatomical studies have demonstrated that sympathetic preganglionic neurones in the intermediolateral cell column receive direct innervation from the diencephalon as well as from the brainstem (Strack et al. 1989). Because baroreceptor afferents are known to project exclusively to the nucleus of the solitary tract (Spyer, 1990), neural impulses travelling to the periphery via a route that bypasses the brainstem may not be subject to baroreceptor-mediated modulation. In anesthetized cats, electrical stimulation of the hypothalamic defence area, an intervention that may be analogous to arousal, can disinhibit cells within the solitary tract nucleus that receive inhibitory input from baroreceptors (Mifflin et al. 1988). In a sleeping human, baroreflex-induced bradycardia was reversed when a K complex occurred during phenylephrine-induced blood pressure elevation (Smyth et al. 1969).

Another possibility is that arousal-induced shortening of burst latency is caused by an alteration in efferent conduction time of sympathetic impulses. The existence of several populations of descending spinal fibres with different conduction velocities provides an anatomical base for this proposition (Jänig & Szulczyk, 1979; Dembowsky et al. 1985). Wallin et al. (1994) observed an inverse relationship between burst amplitude and burst latency during lower body negative pressure. They postulated that when the tonic level of sympathetic activity is enhanced, burst latency could be shortened by variable recruitment of sympathetic fibres with different conduction velocities in a manner analogous to the ‘size principle’ in α-motoneurones (Hennemann & Mendell, 1981). Two lines of evidence suggest that differential recruitment under conditions of heightened sympathetic discharge is not the primary reason for the arousal-induced shortening of burst latency observed in our study. First, we found only a weak correlation between burst amplitude and burst latency in all sympathetic bursts recorded during sleep. Second, even though the frequency and amplitude of sympathetic bursts increased substantially during apnoea, burst latency remained constant until EEG evidence of arousal occurred.

Consequences of arousal-induced alterations in sympathetic outflow and burst latency

K complexes are thought to represent abortive arousals (Roth et al. 1956); nevertheless, they elicit abrupt increases in sympathetic outflow to muscle and skin, heart rate and blood pressure (Hornyak et al. 1991; Takeuchi et al. 1994). We have previously demonstrated that acoustic arousal stimuli cause similar neurocirculatory perturbations and also elicit increases in ventilation (Morgan et al. 1996). It is clear that arousal per se can perturb the cardiovascular and respiratory systems; however, we speculate that the impact of arousal on these systems may be multiplied when arousal occurs in conjunction with sleep-disordered breathing.

In conclusion, arousal from sleep, regardless of whether it occurred spontaneously or was evoked by an apnoea, consistently produced a reduction in sympathetic burst latency. Arousal-induced reduction in sympathetic burst latency may reflect a temporary diminution of baroreflex buffering of sympathetic outflow. If so, this mechanism may explain the observation that the arterial pressure perturbations caused by sleep-disordered breathing are augmented by arousal (Lofaso et al. 1998; Morgan et al. 1998). Thus arousal may play an important role in the short- and long-term cardiovascular consequences of sleep-disordered breathing.

Acknowledgments

The authors thank Dr Basel Taha and Mr Anthony Jacques for expert computer programming. This work was supported by the National Heart, Lung and Blood Institute, the American Heart Association of Wisconsin (Postdoctoral Fellowship for A. Xie), and the Veterans Affairs Research Service. At the time this study was conducted, B. J. Morgan was a Parker B. Francis Fellow in Pulmonary Research.

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