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

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.

Behavioral states in the chronic medullary and midpontine cat.

Behavioral state organization was studied in the caudal portion of chronically maintained cats with transections at the ponto-medullary junction or midpontine level. The cats spent most of their time in a 'quiescent state.' This state was periodically interrupted by 'phasic activations.' During quiescence, ECG and reticular unit activity rates were low and regular. EMG levels resembled those seen during non-REM sleep in intact cats. During phasic activations, unit activity in the nucleus gigantocellularis and neck EMG activity increased to levels seen in the intact cat during active waking. Gross postural changes, vestibular slow phase head nystagmus and head shake reflexes could be observed at these times. No periods of neck muscle atonia were observed in either state. No periods of brain-stem controlled rapid eye movements (REMs) occurred. Unit activity patterns similar to those seen in the intact cat during REM sleep were never observed. Physostigmine administration did not produce REM sleep signs, but rather, triggered an aroused state. Phasic activations occurred in a regular ultradian rhythm, with a period similar to that seen in the REM sleep cycle. We conclude that the chronic medullary cat retains primitive aroused and quiescent states, but does not have any of the local signs of REM sleep. However, the medulla does have the capability of generating ultradian rhythmicities which may contribute to the control of the basic rest activity cycle and the REM, non-REM sleep cycle.

Alterations in blood pressure and REM sleep after pontine carbachol microinfusion.

Infusions of cholinomimetics, either systemically in normal humans, or directly into the brain stem of unanesthetized cats and rats, readily induce rapid eye-movement (REM) sleep. In anesthetized cats and rats, infusions of cholinomimetics have been shown to produce both increases and decreases in arterial blood pressure. We determined the relation of these blood pressure changes to REM sleep, by examining both blood pressure and sleep states after injecting carbachol at midbrain, pontine, and medullary sites in unanesthetized cats. In the pons, carbachol infusions produced an early decrease in blood pressure followed by a sustained hypertensive effect. The early blood pressure decrease was associated with the occurrence of REM sleep; however, higher values were associated with later REM sleep episodes. In other brain stem sites carbachol did not produce REM sleep or its associated reductions in blood pressure. Instead it produced a hypertensive response that increased throughout the 1-h observation period. We hypothesize that pontine muscarinic mechanisms trigger REM sleep and a REM sleep-associated decrease in blood pressure. Thereafter, nicotinic receptors mediating the blood pressure increase override the muscarinic-induced decrease.

Heart rate and blood pressure changes associated with cataplexy in canine narcolepsy.

Blood pressure and heart rate were monitored in narcoleptic dogs by means of a chronically implanted catheter placed in the descending aorta. Changes in these variables were recorded during spontaneously occurring cataplectic episodes. We found no reliable change in blood pressure associated with cataplexy onset. However, heart rate showed a marked increase prior to the onset of cataplexy, with peak heart rates being reached at or shortly after the disappearance of muscle tone. Autonomic events correlated with increased heart rate may contribute to the triggering of cataplexy in narcoleptics.

REM sleep signs rostral to chronic transections at the pontomedullary junction.

The brainstems of 3 cats were transected at the ponto-medullary junction and the cats maintained in stable condition for periods of from 16 to 31 days. After transection, all of these cats had periods in which forebrain sensorimotor cortex, olfactory bulb, hippocampus, eye movement and lateral geniculate recordings exhibited the pattern of activity seen only in REM sleep in the intact cat. We conclude that medullary regions are not required to generate these signs of REM sleep. The pons is necessary for REM sleep and is sufficient to produce REM sleep signs in rostral as well as caudal brain regions. However, the medulla may contribute to regulation of the duration and periodicity of REM sleep.

Rostral brainstem contributes to medullary inhibition of muscle tone.

It has long been known that stimulation of the medial medulla in the decerebrate animal produces bilateral inhibition of muscle tone. In the present study we have found that transection of the brainstem at the ponto-medullary junction attenuates this inhibition. An interaction between medullary and rostal brainstem systems is responsible for the medullary inhibition phenomenon. A similar interaction may produce the inhibition of muscle tone seen in REM sleep.