J. Phyeiol. (1977), 266, pp. 191-207
191
With 5 text-ftgure8 Printed in Great Britain
SLEEP AND RESPIRATION OF RATS DURING HYPOXIA BY J. R. PAPPENHEIMER* From the University Laboratory of Physiology, Oxford
(Received 12 August 1976) SUMMARY
1. The effects of hypoxia on slow-wave sleep (SWS) and of SWS on respiratory responses to hypoxia were investigated on rats provided with chronically implanted cortical electrodes. 2. During the daytime (5-7 hr periods) the proportion of time spent in SWS was 45 %'(s.E. + 10%) when the rats breathed air. Exposure to 10 % 02 (equivalent to 18,000 ft.) reduced this proportion to 27 % (S.E. + 2.5 /). During hypoxia the intensity of e.e.g. activity in SWS (mean, rectified slow-wave voltage) rarely equalled the normal values characteristic of the same rats in fully developed SWS breathing air. The normal pattern of 5-15 min episodes of SWS was changed by hypoxia to a series of brief (2-3 min) incompletely developed episodes. 3. Addition of C02 to inspired gas failed to prevent the reduction of SWS during hypoxia. C02 in normal 02 did not alter sleep significantly. The effects of hypoxia on sleep therefore depend upon changes in 02 pressure rather than upon changes in C02. 4. The effect of SWS on respiration of rats breathing air was to decrease frequency and minute volume by 10-20%. In hypoxia, however, the frequency increased markedly when the animals entered SWS; minute volume was not significantly changed. It follows that stimulation of breathing by hypoxia is greater during SWS than during wakefulness. 5. The anomalous increase of respiratory frequency when hypoxic rats entered SWS was abolished by addition of C02 to the hypoxic gas mixture. 6. Steady-state gaseous metabolism (J02, was decreased 18 + 3 % during hypoxia and was increased 31 + 4 % during exposure to 5 % C02. The implications of these changes for interpretation of respiratory responses to 02 and C02 are discussed.
GO2)
* Career Investigator, American Heart Association on leave from Department of Physiology, Harvard University.
7
PHY 266
192
J. R. PAPPENHEIMER INTRODUCTION
Insomnia is a common complaint of people sojourning at high altitudes but there is no objective evidence that duration or quality of sleep are altered as a result of hypoxia. The problem was described most vividly by Barcroft (1925) in his personal account of reactions to reduced oxygen pressure in the Andes and in a glass chamber in the laboratory, 'In the glass case experiment I had the opportunity of judging a little more exactly of anoxemic sleeplessness than is generally the case. A committee of undergraduate pupils of mine made up their minds that I was never to be left alone; two of them therefore sat up each night outside the case lest help of any sort should be required. I used to ask them in the morning how I had slept and each morning except perhaps the last they said I had slept well. My own view was quite otherwise. I thought I had been awake half the night and was unrefreshed in the morning ... The two opinions can only be reconciled on the hypothesis that whilst I spent most of the night in sleep, the slumber was very light and fitful with incessant dreams. Even some low degree of consciousness which fell short of absolute wakefulness. At Cerro it was the same: measured in hours we slept well but the quality of the sleep in most cases was of an inferior order. The night seemed long and we awoke unrefreshed.' Subsequent accounts of insomnia at altitude are much the same. According to Pugh & Ward (1956 and personal communication) there are subjective sensations of sleeplessness in most unacclimatized individuals at altitudes as low as 10,000 ft; above 18,000 ft even acclimatized individuals usually complain of insomnia and recent experience in the Himalayas suggests that one of the most important benefits of supplementary oxygen derives from its use at night to permit 'sound' sleep. I have investigated this problem on rats, using quantitative methods for evaluating duration and quality of sleep during exposure to various gas mixtures. The results show that duration and depth of sleep are greatly reduced by hypoxia equivalent to an altitude of 18,000 ft breathing air. A second part of the problem (Part II) concerns the effects of sleep on respiratory responses to hypoxia, both with and without added C02. A preliminary account of this work was communicated previously (Pappen-
heimer, 1976). METHODS
I.
Analysi of 81ow-wave sleep (SWS) from cortical potentials Rats were operated under butyrolactone-ether anaesthesia as described by
Goodrich, Greehey, Miller & Pappenheimer (1969). Stainless steel screw electrodes
SLEEP AND RESPIRATION DURING HYPOXIA
193
were implanted in holes drilled through the skull; each rat was provided with symmetrically placed epidural electrodes over right and left frontal and occipital cortex. A fifth electrode over parietal cortex was grounded; it served as reference for differential voltages generated between any pair of the other four electrodes. The electrodes were connected to a miniature socket and embedded in dental cement. Experiments on each rat were carried out at intervals during several months following recovery from the operation. For each experiment the animal was placed in a Perspex chamber as shown in Fig. 1. Connexions between the animal and amplifier were led through a slip ring commutator mounted on a spring-balanced lever within the chamber so that the animal could turn and move freely. Cortical potentials were led through an amplifier and R-C filters giving peak output at 1-65 Hz, down 50 % at 1 and 4 Hz. The filtered output was rectified and the mean rectified voltage
mplifie Apiir1-4ilterHz
R
Slow wave e.e.g. Rectified mean s.w.
V
voltage
Digital integration
of mean s.w. voltage
Pressure 0
(tidal volume)
Glycerine
A Vcal
Spring-loaded cal.
VT=fcalIAp
moat
pipette
XA P
02COanysr Temperature
7-21.
Metered-gas flow
CCCC=
Water or NaOH
Fig. 1. Diagram of apparatus used for quantitative recording of slow wave sleep, respiratory gas exchange and pulmonary ventilation. Only one half of the two compartment differential pressure chamber is shown in the diagram.
recorded as illustrated in Figs. 2 and 5; the mean rectified voltage thus gave continuous measure of the 'depth' of SWS. Finally, the mean rectified voltage was integrated over time using a digital voltage-to-frequency converter; this provided a numerical measure of mean SW voltage over any given interval. The system was calibrated by a 1-65 Hz, 100 1sV peak to peak sine wave delivered to the input of the amplifier. The mean rectified (r.m.s.) voltage of the calibration signal was therefore 35 1W. II. Respiratory mea8urement8 Tidal volume was measured utilizing the principle described by Drorbaugh & Fenn (1955). If an animal is sealed in a non-distensible chamber the pressure in the chamber will increase during inspiration owing to addition of water vapour and body heat to the inspired gas; conversely, the pressure will decrease during expiration 7-2
194
J. R. PAPPENHEIMER
owing to condensation of water vapour and cooling of the expired gas. The tidal volume, 1T, is given by
VT p=
X
{I
(P-) (Prp a)
Tml, BTPS(1
XTJ
where AP is observed change of pressure, AP,,, is observed change of pressure when exactly 1 ml. is injected into chamber, PB is barometric pressure, T', is absolute temperature in chamber, Tb is absolute temperature in lungs, Pw, e is pressure of water vapour in chamber, P'Wb is pressure of water vapour in lungs. In a sealed chamber of the size needed for my experiments the pressure changes caused by respiration of a 300 g rat are less than 0-05 torr. Artifactual changes of pressure of comparable magnitude would be caused by small changes of temperature or by changes in the outside (room) pressure if this were used as reference. In practice the chamber does not have to be sealed provided that inspiratory time is short compared with the time constant of leaks from the chamber. The configuration I used is shown in Fig. 1. The cover of the chamber contained the balanced lever, the slip-ring commutator and electrical leads to the animal. The cover was placed in a glycerine-filled moat on top of the chamber. Owing to its high viscosity (1200 c.p.) the glycerine acts as a rigid, gas-tight seal at all respiratory frequencies. Gas of desired composition is stored in a 300 1. plastic bag subjected to constant pressure by a lead weight. The bag was connected to the chamber through an adjustable valve, a flow-meter and a high resistance nozzle. Gas was simultaneously removed from the chamber by means of a diaphragm pump. Inflow and outflow rates were adjusted to maintain atmospheric pressure within the chamber as measured by the levels of glycerine in the moat. A small amount of methylene blue was added to the glycerine to visualize the meniscus clearly. The chamber consists of two symmetrical compartments, each of volume 7-2 1. and separated by a copper wall to facilitate heat transfer. The rat was placed on a stainless steel screen in one of the two compartments; only this compartment is shown in Fig. 1. The pressure developed between the two halves of the chamber was measured by a strain gauge manometer (Statham Model PM 15 TC). The two halves of the chamber were connected by a no. 21 hypodermic needle; slow pressure artifacts due to changes of temperature, or fluctuations of gas flows were thus equalized between the two chambers. Operational sensitivity was adjusted to the range 1-10 cm deflexion on the recorder per 0-02 torr pressure differential. Calibrations were performed with the rat in place. For this purpose the gain of the pressure amplifier was reduced to 1/5th its normal operational value so that pressure changes due to respiration were minimal. A volume of gas (1 ml.) equal to about 5 times the change of volume associated with the change from a.t.p.s. to b.t.p.s. of each tidal volume was then injected and withdrawn from the rat chamber at various rates, using a precision automatic pipette. At normal gain the value of AP,,, used for equation 1 was then 0-2 times the recorded calibration signal. The impedances to gas flow in and out of the chamber and between its two halves were such that the amplitude of APcl' was not decreased by more than 10% as the speed of injection was slowed from 0-1 to 0-4 sec. The inspiratory phase of a rat's respiratory cycle is less than 0-4 sec. Respiratory minute volume (rV) was calculated as the product of VT and frequency (f ) averaged over 20-50 breaths. Oxygen consumpton (1,o) and CO2 production ('co0) were calculated from the gas flow and steady concentration differences between inflowing and outflowing gas. 02 was measured with a paramagnetic analyzer and CO2 with an infra-red meter. The instruments were calibrated at intervals with known gas mixtures. The volume of the chamber relative to the
SLEEP AND RESPIRATION DURING HYPOXIA
195
gas flow was so large that it was impossible to measure small brief changes of T70 such as those which might possibly occur in alternating states of sleep and quiet wakefulness. However, 10 min periods of grooming or exploratory behaviour were always associated with easily measurable increases of to2 The values of gV0 reported below refer only to states of sleep and quiet wakefulness and it is assumed is approximately the same during these two conditions. that
PO2
III. Gas mixtures Four different compositions of inspired gas were used; nominal compositions were (1) 21 % 02, 0 % CO2 (2) 10 % 02, 0 % CO2 (3) 21 % 02, 5 % CO2 and (4) 10% 02, 4 % CO2. In order to maintain these compositions steadily within the chamber it was necessary to take into account the TO, and co, of the rat in relation to the flow of gas through the chamber. At a flow rate of 200 ml. min-1 the 02 difference was in the range 2-3 % and the CO2 difference was in the range 1-5-2-5 %. 02 concentration in the inflow was made up to be 2-5 % greater than the desired inspired concentration and CO2 was made up to be 20 % less than the desired concentration. Flow rate through the chamber was then adjusted during the experiment until the steady-state outflow composition was within 0 3 % of the nominal inspired concentrations. For experiments in which it was desired to make the inspired gas free of CO2 the floor of the chamber underneath the wire mesh was covered with 2 M-NaOH; CO2 in the outflow did not exceed 0 3 % under these conditions. In all other experiments the floor of the chamber was covered with acidulated water. It was assumed that the inspired gas was saturated with water vapour at the temperature of the chamber. IV. Conduct of experiments Each rat was 'adapted' to the procedures during trial runs breathing air, each run lasting several hours. During these trial runs the e.e.g. was recorded from all possible pairs of electrodes in order to determine which pair provided the greatest difference of mean rectified slow-wave voltage between states of full wakefulness and fully developed slow-wave sleep. In a typical experiment the 'adapted' rat was placed in the chamber and connected to the e.e.g. leads at 9 a.m. The chamber was then flushed with the desired gas mixture and a constant flow of the gas (about 200 ml. min-') was started. Measurements were not begun until the rat was quiet and had been through one or more episodes of fully developed SWS; generally this took 30-90 min. The experimental period was then started and measurements were taken over the ensuing 5-7 h. The mean rectified slow wave component of e.e.g. was recorded without interruption on slowly moving paper (10 mm min-) and the digital readout of cumulative #V. min noted at suitable intervals as illustrated in Fig. 3. Gas comand tco, were noted about every 30 min. positions required for calculation of Respiratory tracings similar to the sample illustrated in Fig. 5 were taken at a paper speed of 250 mm min-. In a typical 6 h experiment at least 20 measurements of respiration were made during periods of sleep and wakefulness. The results to be presented are based on about forty of these 6 h experiments conducted on five male rats between December and June. The rats were exposed to the prevailing light cycle and room temperatures.
TY7.
196
J. R. PAPPENHEIMER RESULTS
PART I. THE EFFECTS OF HYPOXIA ON SLOW-WAVE SLEEP (1) Normal 8leep breathing 21% 02 The daytime sleep of rats normally occurs in episodes of 5-1b min during which the mean rectified slow-wave component of e.e.g. increases substantially (2-5 times the awake value). Towards the end of each episode
E 60I-
Rectified e.e.g.
40
20-
60_60
191
With 5 text-ftgure8 Printed in Great Britain
SLEEP AND RESPIRATION OF RATS DURING HYPOXIA BY J. R. PAPPENHEIMER* From the University Laboratory of Physiology, Oxford
(Received 12 August 1976) SUMMARY
1. The effects of hypoxia on slow-wave sleep (SWS) and of SWS on respiratory responses to hypoxia were investigated on rats provided with chronically implanted cortical electrodes. 2. During the daytime (5-7 hr periods) the proportion of time spent in SWS was 45 %'(s.E. + 10%) when the rats breathed air. Exposure to 10 % 02 (equivalent to 18,000 ft.) reduced this proportion to 27 % (S.E. + 2.5 /). During hypoxia the intensity of e.e.g. activity in SWS (mean, rectified slow-wave voltage) rarely equalled the normal values characteristic of the same rats in fully developed SWS breathing air. The normal pattern of 5-15 min episodes of SWS was changed by hypoxia to a series of brief (2-3 min) incompletely developed episodes. 3. Addition of C02 to inspired gas failed to prevent the reduction of SWS during hypoxia. C02 in normal 02 did not alter sleep significantly. The effects of hypoxia on sleep therefore depend upon changes in 02 pressure rather than upon changes in C02. 4. The effect of SWS on respiration of rats breathing air was to decrease frequency and minute volume by 10-20%. In hypoxia, however, the frequency increased markedly when the animals entered SWS; minute volume was not significantly changed. It follows that stimulation of breathing by hypoxia is greater during SWS than during wakefulness. 5. The anomalous increase of respiratory frequency when hypoxic rats entered SWS was abolished by addition of C02 to the hypoxic gas mixture. 6. Steady-state gaseous metabolism (J02, was decreased 18 + 3 % during hypoxia and was increased 31 + 4 % during exposure to 5 % C02. The implications of these changes for interpretation of respiratory responses to 02 and C02 are discussed.
GO2)
* Career Investigator, American Heart Association on leave from Department of Physiology, Harvard University.
7
PHY 266
192
J. R. PAPPENHEIMER INTRODUCTION
Insomnia is a common complaint of people sojourning at high altitudes but there is no objective evidence that duration or quality of sleep are altered as a result of hypoxia. The problem was described most vividly by Barcroft (1925) in his personal account of reactions to reduced oxygen pressure in the Andes and in a glass chamber in the laboratory, 'In the glass case experiment I had the opportunity of judging a little more exactly of anoxemic sleeplessness than is generally the case. A committee of undergraduate pupils of mine made up their minds that I was never to be left alone; two of them therefore sat up each night outside the case lest help of any sort should be required. I used to ask them in the morning how I had slept and each morning except perhaps the last they said I had slept well. My own view was quite otherwise. I thought I had been awake half the night and was unrefreshed in the morning ... The two opinions can only be reconciled on the hypothesis that whilst I spent most of the night in sleep, the slumber was very light and fitful with incessant dreams. Even some low degree of consciousness which fell short of absolute wakefulness. At Cerro it was the same: measured in hours we slept well but the quality of the sleep in most cases was of an inferior order. The night seemed long and we awoke unrefreshed.' Subsequent accounts of insomnia at altitude are much the same. According to Pugh & Ward (1956 and personal communication) there are subjective sensations of sleeplessness in most unacclimatized individuals at altitudes as low as 10,000 ft; above 18,000 ft even acclimatized individuals usually complain of insomnia and recent experience in the Himalayas suggests that one of the most important benefits of supplementary oxygen derives from its use at night to permit 'sound' sleep. I have investigated this problem on rats, using quantitative methods for evaluating duration and quality of sleep during exposure to various gas mixtures. The results show that duration and depth of sleep are greatly reduced by hypoxia equivalent to an altitude of 18,000 ft breathing air. A second part of the problem (Part II) concerns the effects of sleep on respiratory responses to hypoxia, both with and without added C02. A preliminary account of this work was communicated previously (Pappen-
heimer, 1976). METHODS
I.
Analysi of 81ow-wave sleep (SWS) from cortical potentials Rats were operated under butyrolactone-ether anaesthesia as described by
Goodrich, Greehey, Miller & Pappenheimer (1969). Stainless steel screw electrodes
SLEEP AND RESPIRATION DURING HYPOXIA
193
were implanted in holes drilled through the skull; each rat was provided with symmetrically placed epidural electrodes over right and left frontal and occipital cortex. A fifth electrode over parietal cortex was grounded; it served as reference for differential voltages generated between any pair of the other four electrodes. The electrodes were connected to a miniature socket and embedded in dental cement. Experiments on each rat were carried out at intervals during several months following recovery from the operation. For each experiment the animal was placed in a Perspex chamber as shown in Fig. 1. Connexions between the animal and amplifier were led through a slip ring commutator mounted on a spring-balanced lever within the chamber so that the animal could turn and move freely. Cortical potentials were led through an amplifier and R-C filters giving peak output at 1-65 Hz, down 50 % at 1 and 4 Hz. The filtered output was rectified and the mean rectified voltage
mplifie Apiir1-4ilterHz
R
Slow wave e.e.g. Rectified mean s.w.
V
voltage
Digital integration
of mean s.w. voltage
Pressure 0
(tidal volume)
Glycerine
A Vcal
Spring-loaded cal.
VT=fcalIAp
moat
pipette
XA P
02COanysr Temperature
7-21.
Metered-gas flow
CCCC=
Water or NaOH
Fig. 1. Diagram of apparatus used for quantitative recording of slow wave sleep, respiratory gas exchange and pulmonary ventilation. Only one half of the two compartment differential pressure chamber is shown in the diagram.
recorded as illustrated in Figs. 2 and 5; the mean rectified voltage thus gave continuous measure of the 'depth' of SWS. Finally, the mean rectified voltage was integrated over time using a digital voltage-to-frequency converter; this provided a numerical measure of mean SW voltage over any given interval. The system was calibrated by a 1-65 Hz, 100 1sV peak to peak sine wave delivered to the input of the amplifier. The mean rectified (r.m.s.) voltage of the calibration signal was therefore 35 1W. II. Respiratory mea8urement8 Tidal volume was measured utilizing the principle described by Drorbaugh & Fenn (1955). If an animal is sealed in a non-distensible chamber the pressure in the chamber will increase during inspiration owing to addition of water vapour and body heat to the inspired gas; conversely, the pressure will decrease during expiration 7-2
194
J. R. PAPPENHEIMER
owing to condensation of water vapour and cooling of the expired gas. The tidal volume, 1T, is given by
VT p=
X
{I
(P-) (Prp a)
Tml, BTPS(1
XTJ
where AP is observed change of pressure, AP,,, is observed change of pressure when exactly 1 ml. is injected into chamber, PB is barometric pressure, T', is absolute temperature in chamber, Tb is absolute temperature in lungs, Pw, e is pressure of water vapour in chamber, P'Wb is pressure of water vapour in lungs. In a sealed chamber of the size needed for my experiments the pressure changes caused by respiration of a 300 g rat are less than 0-05 torr. Artifactual changes of pressure of comparable magnitude would be caused by small changes of temperature or by changes in the outside (room) pressure if this were used as reference. In practice the chamber does not have to be sealed provided that inspiratory time is short compared with the time constant of leaks from the chamber. The configuration I used is shown in Fig. 1. The cover of the chamber contained the balanced lever, the slip-ring commutator and electrical leads to the animal. The cover was placed in a glycerine-filled moat on top of the chamber. Owing to its high viscosity (1200 c.p.) the glycerine acts as a rigid, gas-tight seal at all respiratory frequencies. Gas of desired composition is stored in a 300 1. plastic bag subjected to constant pressure by a lead weight. The bag was connected to the chamber through an adjustable valve, a flow-meter and a high resistance nozzle. Gas was simultaneously removed from the chamber by means of a diaphragm pump. Inflow and outflow rates were adjusted to maintain atmospheric pressure within the chamber as measured by the levels of glycerine in the moat. A small amount of methylene blue was added to the glycerine to visualize the meniscus clearly. The chamber consists of two symmetrical compartments, each of volume 7-2 1. and separated by a copper wall to facilitate heat transfer. The rat was placed on a stainless steel screen in one of the two compartments; only this compartment is shown in Fig. 1. The pressure developed between the two halves of the chamber was measured by a strain gauge manometer (Statham Model PM 15 TC). The two halves of the chamber were connected by a no. 21 hypodermic needle; slow pressure artifacts due to changes of temperature, or fluctuations of gas flows were thus equalized between the two chambers. Operational sensitivity was adjusted to the range 1-10 cm deflexion on the recorder per 0-02 torr pressure differential. Calibrations were performed with the rat in place. For this purpose the gain of the pressure amplifier was reduced to 1/5th its normal operational value so that pressure changes due to respiration were minimal. A volume of gas (1 ml.) equal to about 5 times the change of volume associated with the change from a.t.p.s. to b.t.p.s. of each tidal volume was then injected and withdrawn from the rat chamber at various rates, using a precision automatic pipette. At normal gain the value of AP,,, used for equation 1 was then 0-2 times the recorded calibration signal. The impedances to gas flow in and out of the chamber and between its two halves were such that the amplitude of APcl' was not decreased by more than 10% as the speed of injection was slowed from 0-1 to 0-4 sec. The inspiratory phase of a rat's respiratory cycle is less than 0-4 sec. Respiratory minute volume (rV) was calculated as the product of VT and frequency (f ) averaged over 20-50 breaths. Oxygen consumpton (1,o) and CO2 production ('co0) were calculated from the gas flow and steady concentration differences between inflowing and outflowing gas. 02 was measured with a paramagnetic analyzer and CO2 with an infra-red meter. The instruments were calibrated at intervals with known gas mixtures. The volume of the chamber relative to the
SLEEP AND RESPIRATION DURING HYPOXIA
195
gas flow was so large that it was impossible to measure small brief changes of T70 such as those which might possibly occur in alternating states of sleep and quiet wakefulness. However, 10 min periods of grooming or exploratory behaviour were always associated with easily measurable increases of to2 The values of gV0 reported below refer only to states of sleep and quiet wakefulness and it is assumed is approximately the same during these two conditions. that
PO2
III. Gas mixtures Four different compositions of inspired gas were used; nominal compositions were (1) 21 % 02, 0 % CO2 (2) 10 % 02, 0 % CO2 (3) 21 % 02, 5 % CO2 and (4) 10% 02, 4 % CO2. In order to maintain these compositions steadily within the chamber it was necessary to take into account the TO, and co, of the rat in relation to the flow of gas through the chamber. At a flow rate of 200 ml. min-1 the 02 difference was in the range 2-3 % and the CO2 difference was in the range 1-5-2-5 %. 02 concentration in the inflow was made up to be 2-5 % greater than the desired inspired concentration and CO2 was made up to be 20 % less than the desired concentration. Flow rate through the chamber was then adjusted during the experiment until the steady-state outflow composition was within 0 3 % of the nominal inspired concentrations. For experiments in which it was desired to make the inspired gas free of CO2 the floor of the chamber underneath the wire mesh was covered with 2 M-NaOH; CO2 in the outflow did not exceed 0 3 % under these conditions. In all other experiments the floor of the chamber was covered with acidulated water. It was assumed that the inspired gas was saturated with water vapour at the temperature of the chamber. IV. Conduct of experiments Each rat was 'adapted' to the procedures during trial runs breathing air, each run lasting several hours. During these trial runs the e.e.g. was recorded from all possible pairs of electrodes in order to determine which pair provided the greatest difference of mean rectified slow-wave voltage between states of full wakefulness and fully developed slow-wave sleep. In a typical experiment the 'adapted' rat was placed in the chamber and connected to the e.e.g. leads at 9 a.m. The chamber was then flushed with the desired gas mixture and a constant flow of the gas (about 200 ml. min-') was started. Measurements were not begun until the rat was quiet and had been through one or more episodes of fully developed SWS; generally this took 30-90 min. The experimental period was then started and measurements were taken over the ensuing 5-7 h. The mean rectified slow wave component of e.e.g. was recorded without interruption on slowly moving paper (10 mm min-) and the digital readout of cumulative #V. min noted at suitable intervals as illustrated in Fig. 3. Gas comand tco, were noted about every 30 min. positions required for calculation of Respiratory tracings similar to the sample illustrated in Fig. 5 were taken at a paper speed of 250 mm min-. In a typical 6 h experiment at least 20 measurements of respiration were made during periods of sleep and wakefulness. The results to be presented are based on about forty of these 6 h experiments conducted on five male rats between December and June. The rats were exposed to the prevailing light cycle and room temperatures.
TY7.
196
J. R. PAPPENHEIMER RESULTS
PART I. THE EFFECTS OF HYPOXIA ON SLOW-WAVE SLEEP (1) Normal 8leep breathing 21% 02 The daytime sleep of rats normally occurs in episodes of 5-1b min during which the mean rectified slow-wave component of e.e.g. increases substantially (2-5 times the awake value). Towards the end of each episode
E 60I-
Rectified e.e.g.
40
20-
60_60
