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ELECTRICAL SLEEP IN DOGS
Brit. J. Anaesth. (1964), 36, 407
ELECTRICAL SLEEP IN DOGS BY
FLORELLA MAGORA, A. BELLER, AND L. ALADJEMOFF
With the technical assistance of J. TANNENBAUM Departments of Anaesthetics and Neurosurgery, Hadassah Hebrew University Hospital, Jerusalem, Israel
A state of clinical sleep has been obtained in dogs by the passage of an electrical current across the brain. This state was characterized by changes in respiration, posture and other behavioural phenomena typical of physiological sleep. Anaesthesia was not obtained by this method. No ill-effects were noted on prolonged observation of the experimental animals. The response of the central nervous system to direct stimulation by electric current, has been a source of continuous interest and study since the extensive work of Leduc in 1903. It has been shown in experimental animals and also in man that the spread of various electric currents through the brain may cause either (a) reactions of excitation, for example, hyperkinesis, convulsions, respiratory or circulatory changes, or (b) reactions of inhibition, for example, mild drowsiness, sleep, decreased response to stimuli. Reactions of excitation are seen during induction of electrical anaesthesia (Frostig et al., 1944; Knutson, Richy and Reitman, 1956; Hardy, Fabian and Turner, 1961; Tietz et al, 1946; Fabian et al., 1961; Van Harreveld, Plesset and Wiersma, 1942; Knutson, 1954; Van Poznak and Artusio, 1962; Longley, 1949; Thompson, et al., 1944; Rose and Rabinov, 1945; Van Poznak, 1963). Electrical sleep characterized by loss of consciousness without complete anaesthesia is a state in which signs of inhibition only are evoked at the beginning of and during the passage of the electrical current (Burhan, 1959; Gilyarovsky et al., 1958). Electrical sleep may be induced by the application on the intact skull of an interrupted direct current of very low intensity, low frequency and duration. Van Poznak (1963), in a recent review Supported (in part) by a grant from the joint Research Fund of the Hebrew University Hadassah Medical School, Jerusalem.
of electrical anaesthesia,, claimed that the aim of anaesthesia is to obtain a "transient change in the patient's perceptive ability with no post-anaesthetic sequelae". Electrical sleep approaches this aim and has the advantage of not giving rise to the undesirable and unpleasant clinical effects which may occur during electronarcosis. Although electrical sleep does not give good anaesthesia, it may be a valuable experimental tool in the analysis and comprehension of the mechanism of sleep and also of anaesthesia. METHODS AND MATERIALS
Eighteen dogs weighing between 6 and 10 kg were used. Immediately before each experiment, they were given food and water ad libitum. Following food they were usually placed in a cage which allowed free movement, but limited running about. Before and during each experiment the necessary environmental conditions of silence, dim light and absence of sudden movement in the laboratory were enforced. Other extraneous interference was limited as far as possible. Apparatus. The apparatus* used provides either square pulses of current or linear increasing pulses. The pulse duration is variable from 0.1 m.sec to 100 m.sec. The repetition rate is independently variable from 2 pulses/sec to 1000 pulses/sec. *See Appendix, figure 4.
407
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SUMMARY
408
BRITISH JOURNAL OF ANAESTHESIA
A o
1
BWSCLINE
1
o—
(1) A. B. C.
t
0---
FIG. 1 Wave forms of apparatus. Square: (2) Linear increasing pulse: Monopolar pulse. A. Monopolar pulse. Bipolar pulse. B. Bipolar pulse. Monopolar pulse plus direct current C. Monopolar pulse plus direct current
The pulses are variable: monopolar, bipolar or superimposed on direct current of variable level. The wave forms are alterable with no appreciable transient effect. The apparatus was originally built in such a manner as to enable us to study the effects of various forms of currents. All the other forms, excluding the square monopolar pulse wave (fig. 1A), are not further described as they were not used to produce electrical sleep. The voltage received by the animals in our experiments was calculated at a range of 0-10 volts. The apparatus gives a constant voltage for 350-ohm load. The constant voltage output was preferred instead of a constant current stimulation. With the constant current stimulation, high voltage changes appear on the electrodes and may cause pain with any change in resistance due to restlessness of the patient, instability of electrodes, etc. With constant voltage output stimulation, the total voltage on the electrodes does not depend on the subject's resistance.
There is a built-in very fine current regulation control, which allows extremely slow changes of intensity. The current is continuously monitored by a peak-reading milliammeter. The peakcurrent measurement is of importance for two reasons: (1) A current which produces sleep in an experiment can be readily reproduced in following experiments. (2) Bad contact of the electrodes on the scalp is immediately detectable. It is to be noted that the dose of current received by the subject does not depend on the pulse form, pulse duration or frequency. The two electrodes are made of silver, rectangular in shape. One measured 3 x 2 cm, the other 2 x 1.5 cm. The electrodes were placed in the fronto-occipital position described by other investigators (Anan'ev et al., 1960; Smith et al., 1961a, b) (fig. 2).
Downloaded from http://bja.oxfordjournals.org/ at University of California, Santa Barbara on June 26, 2015
PULSE
ELECTRICAL SLEEP IN DOGS
B and C. The same dog during electrical sleep.
Technique. The cathode pole was placed in the frontal region, which is the most sensitive area. The electrodes were placed on saline-soaked cotton pads which were applied directly on the scalp hair. To maintain good stability and steady contact, the electrodes were tied to the head with an elastic band. The cotton was moistened when necessary by further saline, dripped from a syringe. During each experiment, clinical assessments were made of respiration, pulse rate, palpebral reflexes and reactions to various stimuli. In the last four experiments respiration was recorded before and during the experiments with a Statham pressure transducer attached to a Sanborn recorder. The method to record the respiration was as follows. A regular blood pressure cuff was tied to the animal's chest. The cuff was inflated only slightly in order not to limit chest movements, and the communicating tube was connected to the pressure transducer. This method has no absolute quantitative value but it enabled us to show the changes in the pattern of respiration. The actual technique of induction of electrical sleep used was similar to that described by the Russian investigators (Gilyarovsky et al., 1958). During the first 5 minutes, monopolar square pulse current is increased very slowly from 0 to 2.5 milliamps peak according to the response of the dog. The duration of the wave is 1 m.sec and the frequency 100 pulses/sec. When changes occur in the dog's appearance and, especially, in the type of respiration, the current is gradually increased in amplitude and decreased in frequency, simultaneously to between 50 and 20 pulses/sec. Very fine vibrations may be felt on the dog's head. If no outward reaction is noted, the current is further increased until the state of electrosleep is obtained. The maximum current normally required lies between 7 and 12 milliamps peak. The current regulation control built in the apparatus allows very slow changes in intensity and thus prevents unpleasant sensations at the beginning of the passage of the current or during changes of current in the course of the experiment.
Downloaded from http://bja.oxfordjournals.org/ at University of California, Santa Barbara on June 26, 2015
Fio. 2 A. Dog with fronto-occipital electrodes in place for the beginning of the experiment
409
BRITISH JOURNAL OF ANAESTHESIA
OBSERVATIONS
Electrical sleep was achieved in forty-eight experiments and maintained for periods ranging from 30 minutes to 2 hours. Induction time varied between 10 and 30 minutes. Electrical sleep was induced more easily and more rapidly if repeated in the same animal, immediately after his arousal. It is also easier to induce sleep in a dog which has undergone electrosleep repeatedly. This has been observed by other workers (Smith, 1963) during the induction of electroanaesthesia in dogs, and by Russian investigators (Gilyarovsky, et al., 1958) during the induction of electrosleep in adults and children. During the induction period, when the current used was very low (between 2 and 4 millinmps peak), the following changes were noted: the dog
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FIG. 3 Respiratory changes during electrical sleep. A. The respiration before the experiment B. The respiration 15 minutes after the beginning of the experiment. C. The respiration as often observed during electrical sleep.
becomes quiet, his eyelids close repeatedly, respiration slows and becomes regular in rate and amplitude (fig. 3B). With further increase in current intensity and decrease in frequency, and in the absence of interference from external stimuli, the dog begins to lie down by himself (or does not object if helped to lie down) and falls asleep (fig. 2B, C). The upper limit of intensity of the electrical current is established by noting any signs of reaction by the dog. If this critical level is reached, the current must be reduced until signs of irritation disappear. Once electrical sleep was obtained, it could be maintained for as long as the current was applied at the same intensity, frequency and duration. No changes in depth of sleep were noted in spite of variations in the duration of the experiment During this hypnotic stage, the animal still responded to many external stimuli, for example, auditory stimuli, such as dropping a heavy object or clapping hands in the immediate vicinity of the dog. It was noted, however, that the response to distant noises even in the same room was less marked. The dog also responded to olfactory stimuli such as a piece of meat held nearby, and to pain such as pinprick. Repeated stimuli always woke the animaL On cessation of the stimuli the dog sometimes fell asleep again, but occasionally remained awake despite continuation of current flow at levels previously sufficient to maintain sleep. At the completion of the experiment, if the current was suddenly interrupted, the dog would awake immediately and resume his normal behaviour. On some occasions a short period of mild unsteadiness was noted. On the other hand, if the current was gradually reduced to zero and if no external stimuli interfered, the dog would remain asleep. The eyes are closed during electrical sleep. Occasionally conjunctival congestion is noted during the experiment. There are no significant alterations in the pulse rate during electrical sleep. During electrosleep respiration becomes shallower, slower, and regular with short inspiration and prolonged expiration. During the course of electrosleep, the animal lay in a relaxed position, although the peri-ocular
ELECTRICAL SLEEP IN DOGS
411
muscles were occasionally contracted (fig. 2B, c). There was no evidence at any time, even after repeated experiments in the same animal, that the dog remembered the experiment or had unpleasant memories connected with electrosleep.
Downloaded from http://bja.oxfordjournals.org/ at University of California, Santa Barbara on June 26, 2015
of the experiment, will be tolerated if it is reached by gradual increases according to the dog's response. In these experiments, induction is initiated by square wave current at very low intensity and at a rate of 100 pulse/sec. This current has been found to be tolerated well and DISCUSSION adequate for induction. When the first signs of effect are noted, the current is increased and the Using variations in conditioned reflexes and the frequency reduced simultaneously. The reducinterpretations to be gained from them, Pavlov and his school (see Bykov et aL, 1960) developed tion in frequency appears to be of significance the theory that sleep is an active neural process, on deepening the induced sleep and in producing caused by repetitive impulses that have become changes in the respiratory pattern. Russian investiptors (Gilyarovsky et aL, 1958) inhibitory. Other experimental neurophysiohave applied the same form of current to man, logical studies during the past 15 years have but with a lower frequency of 4-20 pulses/sec. In also shown that different impulses from the experimental animals, and also in isolated cat brain, both cortex and medulla, exert nonbrain preparations, similar currents induced specific inhibitory effects on the brain stem reticular formation causing "reticular deactivation" electrocortical synchronization, an equivalent of inhibition (Magnes, or a sleeping state (Moruzzi, 1960; Dell, Bon- electroencephalographic Moruzzi and Pompeiano, 1961). vallet and Hugelin, 1961). Our observation that The elimination of all external stimuli, except sleep may be induced by stimulation of the brain the electric current, is absolutely essential if is consistent with this theory. Sleep is recognized by certain external mani- electrical sleep is to be achieved. It is interesting festations and by a characteristic electroencepha- that even during electrical anaesthesia the dog lographic pattern. The electroencephalogram undergoing abdominal surgery will still respond could not be recorded during the study reported to certain stimuli such as patting (Smith, 1963) here (because of the electric interference genera- or sudden noise. Pavlov's school has shown that ted by the apparatus) so that the interpretation sleep ensues when stimuli which have become of electrical sleep is based on behavioural inhibitory reach the cerebral cortex without any interference from positive conditioned stimuli: characteristics only. During the passage of the electrical current, "If an extraneous stimulus is applied to the the dog remains immobile for prolonged periods experimental animal during the action of an agent of time, although he is able to move. The eyelids which evokes in the cerebral cortex internal are closed, the posture relaxed and natural, inhibition, the process of inhibition disappears response to stimuli is decreased and respiration and the phenomenon is called disinhibition" resembles that noted during chemical anaesthesia (Bykov et al., 1960). This would appear to be the (Wylie.and Churchill-Davidson, 1960) or during reason why electrical sleep cannot be obtained or maintained if the current by itself produces any physiological sleep (Robin, 1958). Signs of autonomic or central nervous system external stimulation; such as twitchings, pain or stimulation, such as salivation, stridor, increased pressure. Furthermore, this explains why a weaker tonus or tachypnoea, were never observed in the current at the commencement of induction is more effective than a stronger one. course of repeated experiments. During further experiments, carried out on The dog does not react to the beginning of the one of the authors (F.M) identical currents were passage of electrical current, presumably because passed with electrodes placed in various positions, die current is not felt. Later, the dog reacts less and less to increases in current, either because of for example, frontal, occipital, mastoidal, temporal habituation to the stimulus or because of a local or ocular. Depending on the position, this anaesthetic effect. For example, a current that will identical current was either not felt at all or procause pain if suddenly induced at the beginning duced severe pain. For this reason, it is felt that
412
BRITISH JOURNAL OF ANAESTHESI
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R,
Helipot control of the pulse height for both pulse forms. S, Selector switch for square and linear increasing pulses. R,a Preset adjusting the linear increasing pulse to the same amplitude as the square pulse. S, Polarity switch for the pulses. S, Polarity switch for the DC component which level is controlled by R.a. M, Peak current meter. M, Measures the DC current
Downloaded from http://bja.oxfordjournals.org/ at University of California, Santa Barbara on June 26, 2015
FIG. 4 Circuit of apparatus.
ELECTRICAL SLEEP IN DOGS
413 REFERENCES
Anan'ev, M. G., Golubeva, I. V., Gurova, L. A., and Khudi, Yu.B. (1960). Preliminary data on experimental electronarcosis induced with apparatus of the scientific research institute of experimental surgical apparatus and instruments. Eksp. Khir., 4, 3 (1957); translated in Aneslhesiology, 21, 215. Burham, S. Ahmed (1959). Some recent developments in pulsed energy sleep. Technical report. Proceedings of Hid annual tri-service conference on biological effects of microwave radiating equipments. Cleveland, Ohio: Rand Development Corporation. Bykov, K. M., Vladimirov, G. Y., Delov, V. Y., Konradi, G. P., and Slonim, A. D. (1960). Textbook of Physiology, p. 632. Ed. Moscow: Foreign Languages Publishing House. Dell, P., Bonvallet, M., and Hugelin, A. (1961). Mechanisms of reticular deactivation. Ciba Foundation Symposium on the Nature of Sleep. p. 86. London: ChurchilL Fabian, L. W., Hardy, J. D., Turner, M., and Moore, F. J. (1961). Electrical anesthesia. Anesth. Analg. Curr. Res., 40, 653. Frostig, J. P., Van Harreveld, A., Reznick, S., Tyler, D. B.. and Wiersma, C A. G. (1944). Electronarcosis in animals and man. Arch. Neurol. Psychiat. (Chic), 51, 232. Gilyarovsky, V. A., Livintzew, N. M., Segal, U. E., and Kinillova, Z. A. (1958). Electroson: a clinicalphysiological investigation. Moscow: Ed. Medical Government Literature. Hardy, J., Fabian, L., and Turner, M. (196IX Electrical anesthesia for major surgery: report of two cases. /. Amer. med. Ass., 175, 599. Knutson, R. C. (1954). Experiments in electronarcosis: preliminary study. Anesthesiology, 15, 551. Richy, F. Y., and Reitman, J. H. (1956). The use of electrical current as an anesthetic agent. Anesthesiology, 17, 815.
APPENDIX KEY TO DIAGRAM (FIO. 4)
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50 picofarad 1 microfarad 1 microfarad 20 microfarad 550 V 40 microfarad 550 V 20 microfarad 550 V 10 microfarad 100 V 80 microfarad 60 V 25 microfarad 10 V 10 Henry 50 micro-amp. 25 milliamp. thyratron tubes 2D 21 electron tube ECC 82 electron tube 6 AL. 5 electron tube 6 J (5 electron tube ECC 82
V V R R R R R R R R R R R R R R R
1 6, ^/ 7 electron tube EL H 8 electron tube EZ 81 1 30 K Helipot la 1 K W.W. 2 1 megohm Linear 3 0.1 megohm 2 watt (preset) 3a 10 K 2 watt (preset) 4 1 K | W 6 0.47 megohm 1W 7 0.16 megohm i w 8 0.65 megohm i w 9 0.1 megohm i w 10 4 4 K i w 11 44 K i w 12 0.5 megohm i w 13 0.5 megohm w 14 2.7 K $w
R R R R R R R R R R R R R R R R R
15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
0.1 megohm i W i 1 megohm 0.51 megohm i w i w 68 K w 0.15 megohm i w 0.1 megohm w 0.1 megohm i w 0.1 megohm i w 0.22 megohm w 350 ohm < w approx. 200 ohm i w shunt resistor 0.1 megohm i w 2 K 2 1 w 1K W W.W. 2K 10 w 10 K 2
w
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the importance of positioning of the electrodes lies not so much in the particular area of cortical cells stimulated by the passage of current, as in the absence or presence of external stimulation engendered by the current. Multiple electrodes, which have been suggested by Van Poznak (1963) and Val Stephen (1959) in the belief that they stimulate specific areas of the brain, may, on the other hand, be effective by reducing the unpleasant localized external effect of the current. Electrical sleep has been induced on repeated occasions in the same animal. In one dog the experiment was repeated 24 times within a 4-month period. No signs of physical damage or behavioural change have been noted following these repeated experiments. Other authors have reported on the results of brain metabolism studies after electrical anaesthesia (Van Harreveld, Tyler and Wiersma, 1943), on histological studies (Knutson, Richy and Reitman, 1956; Smith et aL, 1961b; Silver and Gerard, 1941), on behaviour and electrocardiographic studies before and after passage of the electrical current (Gilyarovsky et al., 1958; Smith et al., 1961b). In none of these studies was any change noted as a result of electrical passage across the brain. This would suggest that the method can be safely applied to human subjects. Experiments in human subjects should be of value in the further investigation and comprehension of the state achieved in animals, in the physiology of sleep and in further research in the field of clinical anaesthesia.
414
Van Harreveld, A., Plesset, M. S., and Wiersma, C. A. G. (1942). Relation between physical properties of electrical currents and their electronarcotic action. Amer. I. Physiol, 137, 39. Tyler, D. B., Wiersma, C. A. G. (1943). Brain metabolism during electronarcosis. Amer. J. Physiol., 139, 171. Van Poznak, A. (1963). Electrical anesthesia. Anesthesiology, 24, 101. Artusio, J. (1962). Effect of stimulus, amplitude, frequency, duration and wave form in production of electronarcosis. "Work in Progress" Abstract, Anesthesiology, 23, 163. Wylie, W. D., and Churchill-Davidson, H. C. (1960). A Practice of Anaesthesia, p. 187, table XXII. Chicago: Year Book. SOMMEIL ELECTRIQUE CHEZ LE CH1EN SOMMAIRE
Un Etat de sommeil electrique a 6t6 obtenu chez le chien par passage d'un courant Electrique a travers le cerveau. Cet Etat Etait caract^risE par des changements de la respiration, de l'attitude et d'autres phenornenes du comportement typiques pour le sommeil physiologique. On n'a pas obtenu une anesthesie par cette methode. On n'a pas observjS de ph^nomenes pathologiques chez les animaux utilises dans cette experience, ceux-ci dtant soumis a des contrdles prolonged. ELEKTRISCHER SCHLAF BEI HUNDEN ZUSAMMENFASSUNG
Mittels Durchstromung des Gehims mit einem elektrischen Strom konnte bei Hunden ein Schlafzustand erzielt werden. Charalrteristische Merkmale dieses Zustandes waren Verfinderungen der Atmung, der Lage und andere Verhaltensphfinomene, die typisch fUr den physiologischen Schlaf sind. Anasthesie konnte durch diese Methode nicht erzielt werden. Wfihrend einer ISngeren Oberwachung der Versuchstiere wurden schgdliche Auswirkungen nicht festgestellt
Downloaded from http://bja.oxfordjournals.org/ at University of California, Santa Barbara on June 26, 2015
Leduc, S. (1903). L'clectrificalion cerebrale Arch. dElect. Med., 11, 403. Longley, E. O. (1949). Electrical anesthesia and electro-narcosis (review article). /. ment. Sci., 95, 51. Magnes, J., Moruzzi, G., and Pompeiano, O. (1961). Electroencephalogram-synchronizing structures in the lower brain stem. Ciba Foundation Symposium on the Nature of Sleep, p. 57. London: Churchill. Moruzzi, G. (1960). Synchronizing influences of the brain stem and the inhibitory mechanisms underlying the production of sleep by sensory stimulation. The Moscow Colloquim Supplement No. 13. The E.E.G. Journal, p. 231. Robin, E. D. (1958). Respiration in sleep. /. din. Invest., 37, 981. Rose, S., and Rabinov, D. (1945). Electrical anaesthesia. Med. J. Aust., 1, 657. Silver, M. L., and Gerard, R. W. (1941). Electrical anesthesia with constant currents. Amer. J. Physiol., 133, 447. Smith, R. H. (1963). Electrical Anesthesia, p. 45. Springfield, Illinois: Thomas. Goodwin, C , Fowler, E., Smith, G. W., and Volpitto, P. P. (1961a). Electronarcosis produced by a combination of direct and alternating current: a preliminary study. Anesthesiology, 22, 163. Gramling, Z. W., Smith, G. W., and Vqlpitto, P. P. (1961b). Electronarcosis by combination of direct and alternating current. Two: Effects on the dog brain as shown by E.E.G. and microscopic study. Anesthesiology, 22, 970. Thompson, G. N., McGinnis, J E., Van Harreveld, A., Wiersma, C. A. G., and Tietz, E. B. (1944). Electronarcosis: clinical comparison with electroshock. War. Med. (Chick.), 6, 158. Tietz, E. S-, Thompson, G. N., Van Harreveld, A., and Wiersma, C. A. G. (1946). Electronarcosis: its application and therapeutic effect in schizophrenia. /. nerv. ment. Dis., 103, 144. Val Stephen (1959). Progress in electrical anaesthesia: a critical review. Med. J. Aust., 1, 831.
BRITISH JOURNAL OF ANAESTHESIA
ELECTRICAL SLEEP IN DOGS BY
FLORELLA MAGORA, A. BELLER, AND L. ALADJEMOFF
With the technical assistance of J. TANNENBAUM Departments of Anaesthetics and Neurosurgery, Hadassah Hebrew University Hospital, Jerusalem, Israel
A state of clinical sleep has been obtained in dogs by the passage of an electrical current across the brain. This state was characterized by changes in respiration, posture and other behavioural phenomena typical of physiological sleep. Anaesthesia was not obtained by this method. No ill-effects were noted on prolonged observation of the experimental animals. The response of the central nervous system to direct stimulation by electric current, has been a source of continuous interest and study since the extensive work of Leduc in 1903. It has been shown in experimental animals and also in man that the spread of various electric currents through the brain may cause either (a) reactions of excitation, for example, hyperkinesis, convulsions, respiratory or circulatory changes, or (b) reactions of inhibition, for example, mild drowsiness, sleep, decreased response to stimuli. Reactions of excitation are seen during induction of electrical anaesthesia (Frostig et al., 1944; Knutson, Richy and Reitman, 1956; Hardy, Fabian and Turner, 1961; Tietz et al, 1946; Fabian et al., 1961; Van Harreveld, Plesset and Wiersma, 1942; Knutson, 1954; Van Poznak and Artusio, 1962; Longley, 1949; Thompson, et al., 1944; Rose and Rabinov, 1945; Van Poznak, 1963). Electrical sleep characterized by loss of consciousness without complete anaesthesia is a state in which signs of inhibition only are evoked at the beginning of and during the passage of the electrical current (Burhan, 1959; Gilyarovsky et al., 1958). Electrical sleep may be induced by the application on the intact skull of an interrupted direct current of very low intensity, low frequency and duration. Van Poznak (1963), in a recent review Supported (in part) by a grant from the joint Research Fund of the Hebrew University Hadassah Medical School, Jerusalem.
of electrical anaesthesia,, claimed that the aim of anaesthesia is to obtain a "transient change in the patient's perceptive ability with no post-anaesthetic sequelae". Electrical sleep approaches this aim and has the advantage of not giving rise to the undesirable and unpleasant clinical effects which may occur during electronarcosis. Although electrical sleep does not give good anaesthesia, it may be a valuable experimental tool in the analysis and comprehension of the mechanism of sleep and also of anaesthesia. METHODS AND MATERIALS
Eighteen dogs weighing between 6 and 10 kg were used. Immediately before each experiment, they were given food and water ad libitum. Following food they were usually placed in a cage which allowed free movement, but limited running about. Before and during each experiment the necessary environmental conditions of silence, dim light and absence of sudden movement in the laboratory were enforced. Other extraneous interference was limited as far as possible. Apparatus. The apparatus* used provides either square pulses of current or linear increasing pulses. The pulse duration is variable from 0.1 m.sec to 100 m.sec. The repetition rate is independently variable from 2 pulses/sec to 1000 pulses/sec. *See Appendix, figure 4.
407
Downloaded from http://bja.oxfordjournals.org/ at University of California, Santa Barbara on June 26, 2015
SUMMARY
408
BRITISH JOURNAL OF ANAESTHESIA
A o
1
BWSCLINE
1
o—
(1) A. B. C.
t
0---
FIG. 1 Wave forms of apparatus. Square: (2) Linear increasing pulse: Monopolar pulse. A. Monopolar pulse. Bipolar pulse. B. Bipolar pulse. Monopolar pulse plus direct current C. Monopolar pulse plus direct current
The pulses are variable: monopolar, bipolar or superimposed on direct current of variable level. The wave forms are alterable with no appreciable transient effect. The apparatus was originally built in such a manner as to enable us to study the effects of various forms of currents. All the other forms, excluding the square monopolar pulse wave (fig. 1A), are not further described as they were not used to produce electrical sleep. The voltage received by the animals in our experiments was calculated at a range of 0-10 volts. The apparatus gives a constant voltage for 350-ohm load. The constant voltage output was preferred instead of a constant current stimulation. With the constant current stimulation, high voltage changes appear on the electrodes and may cause pain with any change in resistance due to restlessness of the patient, instability of electrodes, etc. With constant voltage output stimulation, the total voltage on the electrodes does not depend on the subject's resistance.
There is a built-in very fine current regulation control, which allows extremely slow changes of intensity. The current is continuously monitored by a peak-reading milliammeter. The peakcurrent measurement is of importance for two reasons: (1) A current which produces sleep in an experiment can be readily reproduced in following experiments. (2) Bad contact of the electrodes on the scalp is immediately detectable. It is to be noted that the dose of current received by the subject does not depend on the pulse form, pulse duration or frequency. The two electrodes are made of silver, rectangular in shape. One measured 3 x 2 cm, the other 2 x 1.5 cm. The electrodes were placed in the fronto-occipital position described by other investigators (Anan'ev et al., 1960; Smith et al., 1961a, b) (fig. 2).
Downloaded from http://bja.oxfordjournals.org/ at University of California, Santa Barbara on June 26, 2015
PULSE
ELECTRICAL SLEEP IN DOGS
B and C. The same dog during electrical sleep.
Technique. The cathode pole was placed in the frontal region, which is the most sensitive area. The electrodes were placed on saline-soaked cotton pads which were applied directly on the scalp hair. To maintain good stability and steady contact, the electrodes were tied to the head with an elastic band. The cotton was moistened when necessary by further saline, dripped from a syringe. During each experiment, clinical assessments were made of respiration, pulse rate, palpebral reflexes and reactions to various stimuli. In the last four experiments respiration was recorded before and during the experiments with a Statham pressure transducer attached to a Sanborn recorder. The method to record the respiration was as follows. A regular blood pressure cuff was tied to the animal's chest. The cuff was inflated only slightly in order not to limit chest movements, and the communicating tube was connected to the pressure transducer. This method has no absolute quantitative value but it enabled us to show the changes in the pattern of respiration. The actual technique of induction of electrical sleep used was similar to that described by the Russian investigators (Gilyarovsky et al., 1958). During the first 5 minutes, monopolar square pulse current is increased very slowly from 0 to 2.5 milliamps peak according to the response of the dog. The duration of the wave is 1 m.sec and the frequency 100 pulses/sec. When changes occur in the dog's appearance and, especially, in the type of respiration, the current is gradually increased in amplitude and decreased in frequency, simultaneously to between 50 and 20 pulses/sec. Very fine vibrations may be felt on the dog's head. If no outward reaction is noted, the current is further increased until the state of electrosleep is obtained. The maximum current normally required lies between 7 and 12 milliamps peak. The current regulation control built in the apparatus allows very slow changes in intensity and thus prevents unpleasant sensations at the beginning of the passage of the current or during changes of current in the course of the experiment.
Downloaded from http://bja.oxfordjournals.org/ at University of California, Santa Barbara on June 26, 2015
Fio. 2 A. Dog with fronto-occipital electrodes in place for the beginning of the experiment
409
BRITISH JOURNAL OF ANAESTHESIA
OBSERVATIONS
Electrical sleep was achieved in forty-eight experiments and maintained for periods ranging from 30 minutes to 2 hours. Induction time varied between 10 and 30 minutes. Electrical sleep was induced more easily and more rapidly if repeated in the same animal, immediately after his arousal. It is also easier to induce sleep in a dog which has undergone electrosleep repeatedly. This has been observed by other workers (Smith, 1963) during the induction of electroanaesthesia in dogs, and by Russian investigators (Gilyarovsky, et al., 1958) during the induction of electrosleep in adults and children. During the induction period, when the current used was very low (between 2 and 4 millinmps peak), the following changes were noted: the dog
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FIG. 3 Respiratory changes during electrical sleep. A. The respiration before the experiment B. The respiration 15 minutes after the beginning of the experiment. C. The respiration as often observed during electrical sleep.
becomes quiet, his eyelids close repeatedly, respiration slows and becomes regular in rate and amplitude (fig. 3B). With further increase in current intensity and decrease in frequency, and in the absence of interference from external stimuli, the dog begins to lie down by himself (or does not object if helped to lie down) and falls asleep (fig. 2B, C). The upper limit of intensity of the electrical current is established by noting any signs of reaction by the dog. If this critical level is reached, the current must be reduced until signs of irritation disappear. Once electrical sleep was obtained, it could be maintained for as long as the current was applied at the same intensity, frequency and duration. No changes in depth of sleep were noted in spite of variations in the duration of the experiment During this hypnotic stage, the animal still responded to many external stimuli, for example, auditory stimuli, such as dropping a heavy object or clapping hands in the immediate vicinity of the dog. It was noted, however, that the response to distant noises even in the same room was less marked. The dog also responded to olfactory stimuli such as a piece of meat held nearby, and to pain such as pinprick. Repeated stimuli always woke the animaL On cessation of the stimuli the dog sometimes fell asleep again, but occasionally remained awake despite continuation of current flow at levels previously sufficient to maintain sleep. At the completion of the experiment, if the current was suddenly interrupted, the dog would awake immediately and resume his normal behaviour. On some occasions a short period of mild unsteadiness was noted. On the other hand, if the current was gradually reduced to zero and if no external stimuli interfered, the dog would remain asleep. The eyes are closed during electrical sleep. Occasionally conjunctival congestion is noted during the experiment. There are no significant alterations in the pulse rate during electrical sleep. During electrosleep respiration becomes shallower, slower, and regular with short inspiration and prolonged expiration. During the course of electrosleep, the animal lay in a relaxed position, although the peri-ocular
ELECTRICAL SLEEP IN DOGS
411
muscles were occasionally contracted (fig. 2B, c). There was no evidence at any time, even after repeated experiments in the same animal, that the dog remembered the experiment or had unpleasant memories connected with electrosleep.
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of the experiment, will be tolerated if it is reached by gradual increases according to the dog's response. In these experiments, induction is initiated by square wave current at very low intensity and at a rate of 100 pulse/sec. This current has been found to be tolerated well and DISCUSSION adequate for induction. When the first signs of effect are noted, the current is increased and the Using variations in conditioned reflexes and the frequency reduced simultaneously. The reducinterpretations to be gained from them, Pavlov and his school (see Bykov et aL, 1960) developed tion in frequency appears to be of significance the theory that sleep is an active neural process, on deepening the induced sleep and in producing caused by repetitive impulses that have become changes in the respiratory pattern. Russian investiptors (Gilyarovsky et aL, 1958) inhibitory. Other experimental neurophysiohave applied the same form of current to man, logical studies during the past 15 years have but with a lower frequency of 4-20 pulses/sec. In also shown that different impulses from the experimental animals, and also in isolated cat brain, both cortex and medulla, exert nonbrain preparations, similar currents induced specific inhibitory effects on the brain stem reticular formation causing "reticular deactivation" electrocortical synchronization, an equivalent of inhibition (Magnes, or a sleeping state (Moruzzi, 1960; Dell, Bon- electroencephalographic Moruzzi and Pompeiano, 1961). vallet and Hugelin, 1961). Our observation that The elimination of all external stimuli, except sleep may be induced by stimulation of the brain the electric current, is absolutely essential if is consistent with this theory. Sleep is recognized by certain external mani- electrical sleep is to be achieved. It is interesting festations and by a characteristic electroencepha- that even during electrical anaesthesia the dog lographic pattern. The electroencephalogram undergoing abdominal surgery will still respond could not be recorded during the study reported to certain stimuli such as patting (Smith, 1963) here (because of the electric interference genera- or sudden noise. Pavlov's school has shown that ted by the apparatus) so that the interpretation sleep ensues when stimuli which have become of electrical sleep is based on behavioural inhibitory reach the cerebral cortex without any interference from positive conditioned stimuli: characteristics only. During the passage of the electrical current, "If an extraneous stimulus is applied to the the dog remains immobile for prolonged periods experimental animal during the action of an agent of time, although he is able to move. The eyelids which evokes in the cerebral cortex internal are closed, the posture relaxed and natural, inhibition, the process of inhibition disappears response to stimuli is decreased and respiration and the phenomenon is called disinhibition" resembles that noted during chemical anaesthesia (Bykov et al., 1960). This would appear to be the (Wylie.and Churchill-Davidson, 1960) or during reason why electrical sleep cannot be obtained or maintained if the current by itself produces any physiological sleep (Robin, 1958). Signs of autonomic or central nervous system external stimulation; such as twitchings, pain or stimulation, such as salivation, stridor, increased pressure. Furthermore, this explains why a weaker tonus or tachypnoea, were never observed in the current at the commencement of induction is more effective than a stronger one. course of repeated experiments. During further experiments, carried out on The dog does not react to the beginning of the one of the authors (F.M) identical currents were passage of electrical current, presumably because passed with electrodes placed in various positions, die current is not felt. Later, the dog reacts less and less to increases in current, either because of for example, frontal, occipital, mastoidal, temporal habituation to the stimulus or because of a local or ocular. Depending on the position, this anaesthetic effect. For example, a current that will identical current was either not felt at all or procause pain if suddenly induced at the beginning duced severe pain. For this reason, it is felt that
412
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FIG. 4 Circuit of apparatus.
ELECTRICAL SLEEP IN DOGS
413 REFERENCES
Anan'ev, M. G., Golubeva, I. V., Gurova, L. A., and Khudi, Yu.B. (1960). Preliminary data on experimental electronarcosis induced with apparatus of the scientific research institute of experimental surgical apparatus and instruments. Eksp. Khir., 4, 3 (1957); translated in Aneslhesiology, 21, 215. Burham, S. Ahmed (1959). Some recent developments in pulsed energy sleep. Technical report. Proceedings of Hid annual tri-service conference on biological effects of microwave radiating equipments. Cleveland, Ohio: Rand Development Corporation. Bykov, K. M., Vladimirov, G. Y., Delov, V. Y., Konradi, G. P., and Slonim, A. D. (1960). Textbook of Physiology, p. 632. Ed. Moscow: Foreign Languages Publishing House. Dell, P., Bonvallet, M., and Hugelin, A. (1961). Mechanisms of reticular deactivation. Ciba Foundation Symposium on the Nature of Sleep. p. 86. London: ChurchilL Fabian, L. W., Hardy, J. D., Turner, M., and Moore, F. J. (1961). Electrical anesthesia. Anesth. Analg. Curr. Res., 40, 653. Frostig, J. P., Van Harreveld, A., Reznick, S., Tyler, D. B.. and Wiersma, C A. G. (1944). Electronarcosis in animals and man. Arch. Neurol. Psychiat. (Chic), 51, 232. Gilyarovsky, V. A., Livintzew, N. M., Segal, U. E., and Kinillova, Z. A. (1958). Electroson: a clinicalphysiological investigation. Moscow: Ed. Medical Government Literature. Hardy, J., Fabian, L., and Turner, M. (196IX Electrical anesthesia for major surgery: report of two cases. /. Amer. med. Ass., 175, 599. Knutson, R. C. (1954). Experiments in electronarcosis: preliminary study. Anesthesiology, 15, 551. Richy, F. Y., and Reitman, J. H. (1956). The use of electrical current as an anesthetic agent. Anesthesiology, 17, 815.
APPENDIX KEY TO DIAGRAM (FIO. 4)
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the importance of positioning of the electrodes lies not so much in the particular area of cortical cells stimulated by the passage of current, as in the absence or presence of external stimulation engendered by the current. Multiple electrodes, which have been suggested by Van Poznak (1963) and Val Stephen (1959) in the belief that they stimulate specific areas of the brain, may, on the other hand, be effective by reducing the unpleasant localized external effect of the current. Electrical sleep has been induced on repeated occasions in the same animal. In one dog the experiment was repeated 24 times within a 4-month period. No signs of physical damage or behavioural change have been noted following these repeated experiments. Other authors have reported on the results of brain metabolism studies after electrical anaesthesia (Van Harreveld, Tyler and Wiersma, 1943), on histological studies (Knutson, Richy and Reitman, 1956; Smith et aL, 1961b; Silver and Gerard, 1941), on behaviour and electrocardiographic studies before and after passage of the electrical current (Gilyarovsky et al., 1958; Smith et al., 1961b). In none of these studies was any change noted as a result of electrical passage across the brain. This would suggest that the method can be safely applied to human subjects. Experiments in human subjects should be of value in the further investigation and comprehension of the state achieved in animals, in the physiology of sleep and in further research in the field of clinical anaesthesia.
414
Van Harreveld, A., Plesset, M. S., and Wiersma, C. A. G. (1942). Relation between physical properties of electrical currents and their electronarcotic action. Amer. I. Physiol, 137, 39. Tyler, D. B., Wiersma, C. A. G. (1943). Brain metabolism during electronarcosis. Amer. J. Physiol., 139, 171. Van Poznak, A. (1963). Electrical anesthesia. Anesthesiology, 24, 101. Artusio, J. (1962). Effect of stimulus, amplitude, frequency, duration and wave form in production of electronarcosis. "Work in Progress" Abstract, Anesthesiology, 23, 163. Wylie, W. D., and Churchill-Davidson, H. C. (1960). A Practice of Anaesthesia, p. 187, table XXII. Chicago: Year Book. SOMMEIL ELECTRIQUE CHEZ LE CH1EN SOMMAIRE
Un Etat de sommeil electrique a 6t6 obtenu chez le chien par passage d'un courant Electrique a travers le cerveau. Cet Etat Etait caract^risE par des changements de la respiration, de l'attitude et d'autres phenornenes du comportement typiques pour le sommeil physiologique. On n'a pas obtenu une anesthesie par cette methode. On n'a pas observjS de ph^nomenes pathologiques chez les animaux utilises dans cette experience, ceux-ci dtant soumis a des contrdles prolonged. ELEKTRISCHER SCHLAF BEI HUNDEN ZUSAMMENFASSUNG
Mittels Durchstromung des Gehims mit einem elektrischen Strom konnte bei Hunden ein Schlafzustand erzielt werden. Charalrteristische Merkmale dieses Zustandes waren Verfinderungen der Atmung, der Lage und andere Verhaltensphfinomene, die typisch fUr den physiologischen Schlaf sind. Anasthesie konnte durch diese Methode nicht erzielt werden. Wfihrend einer ISngeren Oberwachung der Versuchstiere wurden schgdliche Auswirkungen nicht festgestellt
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Leduc, S. (1903). L'clectrificalion cerebrale Arch. dElect. Med., 11, 403. Longley, E. O. (1949). Electrical anesthesia and electro-narcosis (review article). /. ment. Sci., 95, 51. Magnes, J., Moruzzi, G., and Pompeiano, O. (1961). Electroencephalogram-synchronizing structures in the lower brain stem. Ciba Foundation Symposium on the Nature of Sleep, p. 57. London: Churchill. Moruzzi, G. (1960). Synchronizing influences of the brain stem and the inhibitory mechanisms underlying the production of sleep by sensory stimulation. The Moscow Colloquim Supplement No. 13. The E.E.G. Journal, p. 231. Robin, E. D. (1958). Respiration in sleep. /. din. Invest., 37, 981. Rose, S., and Rabinov, D. (1945). Electrical anaesthesia. Med. J. Aust., 1, 657. Silver, M. L., and Gerard, R. W. (1941). Electrical anesthesia with constant currents. Amer. J. Physiol., 133, 447. Smith, R. H. (1963). Electrical Anesthesia, p. 45. Springfield, Illinois: Thomas. Goodwin, C , Fowler, E., Smith, G. W., and Volpitto, P. P. (1961a). Electronarcosis produced by a combination of direct and alternating current: a preliminary study. Anesthesiology, 22, 163. Gramling, Z. W., Smith, G. W., and Vqlpitto, P. P. (1961b). Electronarcosis by combination of direct and alternating current. Two: Effects on the dog brain as shown by E.E.G. and microscopic study. Anesthesiology, 22, 970. Thompson, G. N., McGinnis, J E., Van Harreveld, A., Wiersma, C. A. G., and Tietz, E. B. (1944). Electronarcosis: clinical comparison with electroshock. War. Med. (Chick.), 6, 158. Tietz, E. S-, Thompson, G. N., Van Harreveld, A., and Wiersma, C. A. G. (1946). Electronarcosis: its application and therapeutic effect in schizophrenia. /. nerv. ment. Dis., 103, 144. Val Stephen (1959). Progress in electrical anaesthesia: a critical review. Med. J. Aust., 1, 831.
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