Heart rate and blood pressure changes during sleep-waking cycles and cataplexy in narcoleptic dogs

Abstract

Cataplexy is the abrupt loss of muscle tone experienced by narcoleptics. It is usually precipitated by strong emotions or athletic activity. It has been hypothesized that cardiovascular variables have a role in the triggering of cataplexy. In the present study, we have utilized the narcoleptic canine model to directly investigate changes in heart rate and blood pressure in relation to cataplectic episodes. We found that heart rate increased 18% on average in the 20 s preceding cataplexy onset and then fell during cataplexy. Thus, from a cardiovascular standpoint, cataplexy can be subdivided into two very different periods, the cataplexy onset period with very high and declining heart rate, and the period greater than or equal to 10 s after onset, with greatly reduced heart rate. Heart rate at cataplexy onset was significantly higher than heart rate in rapid-eye-movement (REM) sleep, non-REM sleep, and quiet waking. Blood pressure did not markedly change before the onset of spontaneous cataplexies but decreased significantly during cataplexy. Although blood pressure increases did not precede spontaneous cataplexies, sudden increases in blood pressure, induced pharmacologically or by obstruction of the descending aorta, triggered cataplexy in the most severely affected subjects. A hypothesized role for cataplexy as a homeostatic reflex, triggered by interactions between blood flow, central chemoreceptors, and atonia control mechanisms in the medial medulla, is discussed.

FIG. 1.

Heart rate as a function of state ± SE in dogs 139,141,and 142. W, waking; CAT, cataplexy; REM, rapid-eye movement; NREM, non-REM.

FIG. 2.

Systolic blood pressure (BP) as a function of state. See Fig. 1 for abbreviations.

FIG. 3.

Diastolic blood pressure (BP) as a function of state. See Fig. 1 for abbreviations.

FIG. 4.

Time course of changes in heart rate, blood pressure (BP), and nuchal muscle tone as a function of percentage of cataplexy interval completed in dogs 139, 141, and 142. Mean duration of entire cataplexy interval is indicated for each dog. EMG, electromyogram.

FIG. 5.

Time course of changes in heart rate and blood pressure (BP) during 10 s before and after cataplexy onset.

FIG. 6.

Effect of norepinephrine administration on frequency of cataplexy attacks. Blood pressure (BP) in mmHg. “Wake with cataplexy,” percentage of waking episodes in which one or more cataplectic attacks occurred; EMG, voltage of nuchal electromyogram. EMG reflects average muscle activity across each interval. Because intervals with short periods of cataplexy have considerable tone before and after attacks, average EMG activity does not mirror “wake with cataplexy” values.

fig. 7.

Effect of sodium nitroprusside administration on frequency of cataplexy attacks. % Wake with cataplexy, percentage of waking episodes in which one or more cataplectic attacks occurred; % Cataplexy, percentage of episodes in which cataplexy, defined as complete loss of nuchal muscle tone, occupied >50% of the 1-min epoch; % Wake, percentage of episodes with waking, uninterrupted by cataplexy.

FIG. 8.

Triggering of cataplexy by obstruction of descending aorta. Top electromyogram (EMG) tracing is from right, and bottom trace is from left neck muscles. Respiration is from thoracic strain gauge (inspiration up). EEG, electroencephalogram; EOG, electrooculogram; BP, blood pressure; HR, heart rate. First arrow, time of inflation of aortic balloon; 2nd arrow, time of deflation of balloon.

FIG. 9.

Percentage of episodes with cataplexy before, during, and after inflation of aortic balloon, as shown in Fig. 8.