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The effects of O2 and CO2 and of ambient temperature on ventilatory patterns of dogs
Respiration Physiology, (1972) 16, 79-91; North-Holland Pubiishi~g Company, Amsterdam
THJI EFFECTS OF Oz AND CO2 AND OF AMJHENT TEMPERATUREl ON VENTILATORY PATTERNS OF DOGS’
D. B. JENNINGS*
and R. D. MACKLIN
Department of Physiology, Queen’s University, Kingston, Ontario, Canada
Abetract, Interrelationships between minute ventilation and respiratory rate were examined in conscious dogs at rest and during exercise. Studies were carried out at both cool (19-23 “C) and warm (27-32 “C) ambient temperatures while the dogs breathed room air or different mixtures of O2 and COz. The relation between respiratory rate and minute v~t~tion in a cool room was sigmoidal with a mean respiratory rate of 15 breaths per minute when the mean ventilation was 2.9 L per minute and with a mean respiratory rate of 276 breaths per minute when the mean ventilation was 27.5 L per minute. This fundamental sigmoidal relation in the cool room was shifted to the right slightly by breathing 10 ‘A0, or by light exercise and more markedly by breathing 5 % COs. In a warm room the patterns established in the cool room were shifted to the left. The respiratory response of the animals to a change in the inspired oxygen or carbon dioxide mixture was shown to depend on the initial frequency-ventilation relation. Breathing pattern Control of breathing Dogs
Hypercapnia Hypoxia Thermal polypnoea
Human subjects have a fixed relationship between minute ventilation and respiratory rate for quite a number of stimuli except for increased body temperature where respiratory rate is increased for a given minute ventilation (Hey et al., 1966). In contrast, in the conscious dog, which pants with frequencies up to 300-400 breaths per minute (Sc~dt-Niel~n, 1964), Richet (1898) noted that asphyxia or carbon dioxide prevented tachypnoea. Anrep and Hammouda (1932) also noted that in panting anaesthetized dogs, the inhalation of carbon dioxide caused a decrease in respiratory rate, whereas, anoxia was found to have no effect on respiratory rate. We have found that some conscious resting dogs acclimated to an ambient temperature of 20 “C and by many criteria in a steady state panted consistently despite the Accepted for publication 15 April 1972. ’ Supported by grants to D. B. Jennings from the Defence Research Board of Canada and the Ontario Heart Foundation. 2 Senior Research Fellow, Canadian Heart Foundation (1964-1970).
79
80
D. B. JENNINGS
AND R. D. MACKLIN
cool temperature. Other dogs exposed to the same conditions breathed at low ventilations and low respiratory rates. Still other animals panted in some studies but on other days were non-panters. Analysis of respiration in these dogs breathing air indicated a predictable continuous pattern of respiratory rate with respect to minute ventilation. When these dogs were subjected to stimuli such as increased ambient temperature, exercise, hypercapnia or hypoxia there were significant changes in the patterns of respiratory rate and minute ventilation. Methods Seven male mongrel dogs, 19-29 kg body weight, were prepared with chronic tracheostomies (Thilenius and Vial, 1963). In the studies an endotracheal tube with an inflatable cuff was placed in the trachea and connected to an Ambu two-way valve. The inspiratory resistance of the valve was 2 cm of water/L/set and expiratory resistance was 4 cm of water/L/set. The dead space of the endotracheal tube plus the Ambu valve was 26 ml. The dogs inspired either room air or a gas mixture from a large balloon at ambient pressure. Expired gas was collected in a Tissot spirometer and the minute ventilation (BTPS) determined. Respiratory rate was determined from expiratory air flow monitored with a Fleisch pneumotach and a Statham PM15 or a Pace P7 differential transducer. STUDIES
IN DOGS AT REST
Four groups of resting studies were carried out in each of the seven dogs between June and September over a 2 year period. Two different ranges of laboratory temperature were provided for the experiment : a. a cool room with a temperature range of 19-23 “C and b. a warm room with a temperature range of 27-32 “C. The dogs were brought to the laboratory at least one hour prior to the experiment, the endotracheal tube introduced, and the other adjustments for measurements made. Then the dog was allowed to sit or lie quietly on a treadmill. When the experiment was started, the animal was monitored for at least 10 min while breathing room air and then for two successive 10-15 minute periods while breathing: a. a mixture of 10% oxygen! followed by 10% oxygen + 5% carbon dioxide ; followed by room air, or b. 5% carbon dioxide in air ; followed by 5% carbon dioxide in 80% oxygen ; followed by room air. In each experiment the minute to minute changes in minute ventilation and respiratory rate were determined. STUDIES
IN DOGS DURING
EXERCISE
At the cool ambient temperature, measurements of respiratory rate and minute ventilation were made in 6 of the 7 animals while they walked at 1 mph on the treadmill. In all exercise experiments the dogs breathed room air for the first 30 min and measurements were made at lo,20 and 30 min. The experiment then took two forms :
VENTILATORY
81
PATTERNS OF DOGS
in 9 experiments the 6 animals continued to breathe room air ; whereas, in 13 experiments the animals were switched to inhale 5% CO, in air. In this second part of the experiment, respiratory measurements were made for up to 60 min at 5-10 minute intervals. ResuIts I. RESPIRATORY RATE IN DOGS BREATHING AND CARBON DIOXIDE (figs. 1 and 2)
THE VARIOUS
RESTING
COOL
MIXTURES
OF OXYGEN
DOGS
ROOM
ooa#l
x
#3*
#“:: 300
#6A #70 #SO
2oc
~P~AT~Y RATE 1oc
breaths/min.
( WARM
ROOM
Fig. 1. The minute to minute variations in respiratory rate iu dogs breathing room air, followed oy 5% COz in air (20% 0,), followed by 5% COz with 80% 0,, followed by room air. The same dogs were studied in both a cool room and a warm room.
82
D. B. JENNINGS AND R. D. MACKLIN
RESTING
DOGS
COOL
ROOM
Dog#l
x #3*
RESPIRATORY RATE
breatk/min.
1oG
o WARM
ROOM
1ocI-
0
AIR -10
-5
1
AIR 0
5
10
15
TIME
5
10
15
5
IO
15
20
25
I 30
(minutes)
Fig. 2. The minute to minute variations in respiratory r&e in dogs breathing room air followed by 10% oxygen, followed by 10% 0, with 5% COz, followed by room air in both a cool room and a warm room.
In the first columns of figs. 1 and 2, the respiratory rates of dogs breathing room air at cool and warm ambient conditions are plotted for the 10 min preceding breathing the different gas mixtures. In general when breathing room air, a non-panting dog (respiratory rate < 100 breaths per minute) had very little variation in respiratory rate whereas a panting dog (respiratory rate > 100 breaths per minute) had a much more variable respiratory rate per minute. However, the variation in respiratory frequency seen in tachypnoeic animals was confined within a range and it was unusual to see an animal that was breathing rapidly suddenly breathe slowly. In fig. 1, it can be seen that panting dogs had a decrease in respiratory rate when
VENTILATORY
PATTERNS OF DOGS
83
breathing 5% COz in both cool and ,warm rooms. When the oxygen level was increased from 20% to 80% O2 in the 5% CO, mixture there was no apparent effect of the high oxygen level on the respiratory rate. When 10% oxygen was breathed in a cool room (fig. 2) panting dogs responded by a slight decrease in respiratory rate. However, in the warm room, a similar decrease in respiratory rate in panting dogs was not observed when breathing 10% oxygen (fig. 2). In both the cool and warm rooms, the addition of 5 % CO* to the 10% oxygen resulted in a comparable marked decrease in respiratory rate in panting dogs. Slowly breathing dogs, as shown in both figs. 1 and 2, generally had relatively small and variable increases in respiratory rate with hypoxia or hypercapnia. In panting dogs, the responses as described indicate an order or priority for stimuli in determin~g the degree of tachypnoea. Hypercapnia was an overriding stimulus since it depressed respiratory rate in the warm as well as the cool room. Thermal stress was second in importance since tachypnoea appeared to be maintained in the warm room during the same anoxic stimulus which had lowered respiratory rate in the cool room. Thirdly, anoxia depressed respiratory rate in the panting dogs in the cool room. II. VENTILATORY (figs. 3a, b, and c)
RESPONSES
OF INDIVIDUAL
DOGS TO VARIOUS
GAS MIXTURES
The most striking finding was the enormous variability in the ventilatory patterns between dogs breathing the same gas mixtures. In this section we will examine two examples, figs. 3a and 3b, where the dogs breathed with entirely diierent patterns. Then we will describe the ventilatory pattern of another dog (fig. 3~)which, within the course of a study, switched from pattern type 3a to pattern type 3b. In these examples, minute to minute observations of minute ventilation with relation to respiratory rate are plotted for conditions where the dogs breathed room air, 10% 02, and 10% 0, with 5% CO, in a cool room. The proportions of the axis in all three plots are the same and in fig. 3a, the areas of observations contained in fig. 3b and 3c are outlined. Within each figure an arrow joins the last minute of breathing a given gas mixture with the first minute of breathing another gas mixture. In some cases additional arrows show the change in pattern with time during the breathing of a gas mixture. Figure 3a shows a dog that was breathing with a high respiratory rate approaching 300 breaths per minute on room air. When switched to 10% 0, the animal had minimal changes in minute ventilation but any given ventilation was attained at a lower respiratory rate. When breathing 10% O2 with 5% COz the animal increased ventilation but with a marked reduction in respiratory rate. Figure 3b depicts the ventilatory pattern changes in a dog breathing at a low respiratory rate in room air. When this animal breathed 10% 0, an initial increase in minute ventilation and respiratory rate was followed by a return towards control. When 5% CO2 was breathed with 10% O2 an increased ventilation was accomplish~ with smaller increases in respiratory rate at any given ventilation than seen with the 10% 0, alone.
(a)
Cool Room
Dog 88
84
RESPIRATORY RATE
*OO-
( breaths / min.1 ,oo_ ---/-
3_B
( litres /minute
VENTILATION
1
Cool Room
(b)
RESPIRATORY RATE
b
(4
lb VENTILATION
% ( litres /minute I
sb
d3
Cool Room
Dow3
a-ROOMAIR *
IO?+
Y wxq+5r.cq
RESPIRATORY RATE ereatw/mkb)
4
rb
&a
VENTILATION
bb
4ki
(I/min.f
Figs. 3a, b, c. Plots of respiratory rate versus minute ventilation with the symbols representing minute to minute pairs of data. The last minute of breathing a given mixture is joined to the first and in some cases subsequent minutes of breathing a different gas mixture. The examples are from three different dogs with different resting respiratory rates when breathing room ah in a cool room. Figures 3a and 3b demonstrate the marked differences in response between dogs which are slowly breathing and dogs which are tachypnoeic Figure 3c demonstrates that a dog can shift during the course of a study from breathing rapidly to breathing slowly and therefore can change from the pattern of 3a into the pattern of 3b. The areas covered by graphs 3b and 3c are shown on graph 3a.
VENTILATORY
PATTERNS OF DOGS
85
In fig. 36, a dog, which started out on air breathing at a high respiratory rate like example 3a, went through changes of pattern breathing 10% O2 and 10% O2 with 5% COz that were in-between examples 3a and 3b. Finally, during recovery on room air this dog breathed slowly as in 3b. Thus, this animal shifted from panting to nonpanting during these ventilatory stimuli. III. COMPOSITE VENTILATORY PATTERNS IN DOGS BREATHING DIFFERENT GAS MIXTURES AT REST UNDER DIFFERENT AMBIENT TEMPERATURES AND DURING EXERCISE (tigs. 4, 5, 6)
Despite the enormous variability between the breathing patterns of different dogs and even within some dogs, a unifying concept emerged when the data for all seven dogs were compiled. The mean respiratory rate was analyzed for 5 L ranges of minute ventilation. In figs. 4,5 and 6 respiratory rate per minute + 95% confidence limits is plotted against the mean minute ventilation. The small numbers beside the points indicate the number of observations analyzed at each point. Lines of best fit, drawn by eye, join the points repre~ntative of an in~vid~l set of conditions. Figure 4 represents the patterns of respiratory rate for minute ventilation in dogs breathing room air both at rest in a cool or warm room and while exercising in a cool room. The striking finding is the difference in respiratory pattern with respect to minute ventilation with a change in ambient temperature or with exercise. At rest in a cool room the respiratory rate rises rapidly between ventilations of 2.9 L per minute and 23 L per minute and then there is a relatively small change in frequency for further increases in minute ventilation. A thermal stress at rest shifts the pattern to the left INSPIRED GAS-ROOM
t
RESl,W+RM ROOM 0 REST,COOL ROOM 0 EXERCiSE.COOL -
AIR
300,
2
RESPIRATORY RATE breaths / min.1
204
100
+95% confiie
limits
300
50
~
VENTILATION
( litres/
minute
)
Fig. 4. Compiled data for 7 resting dogs breathing room air at rest in a cool room (e) and a warm room (*) and duringexercise in a cool room (0). The mean respiratory rates f 95% confidence limits were determined for 5 L ranges of minute ventilation. The number of pairs of data used in calculating each point is listed beside the symbol.
D. B. JENNINGS AND R. D. MACKLIN
Fig. 5. Compiled data for 7 dogs breathing room air at rest in a cool room (0) and breathing 5% CO, in air at rest in a cool room (A), 5% CO, in air at rest in a warm room (0) and during exercise in a cool room (I-J). The conventions used are the same as in fig. 4.
RESPIRATORY RATE breaths /min. ?95% confidence
limits
“d
4
Ib
b
h
rb VENTIl_ATIt$U
*
48
@a
c4
80
(titroa/mkte)
Fig. 6. Compiled data for 7 resting dogs breathing room air in a cool room (a), breathing 10% in both cool (0) and warm (*) rooms, and breathing 10% O2 with 5% CO2 in both cool (0) and warm (A) rooms. The conventions used are the same as in fig. 4.
over the lower range of ventilation. During exercise in a cool room the pattern is shifted to the right. Figure 5 depicts the effects of hypercapnia on the resting pattern. Five per cent CO2 in air causes a marked shift in the pattern to the right in resting dogs. The hypercapnic respiratory pattern is not affected by exercise but is shifted to the left by an increase in ambient temperature. The effects of hypoxia on the respiratory pattern are shown in fig. 6. A decrease in inspired O2 to 10% resulted in a small shift in the pattern to the right. When 10%
b¶
VENTILATORY
PATTERNS OF DOGS
87
O2 and 5% CO2 was inhaled, the effect of the carbon dioxide was to again cause a shift in the curve to the right almost identical to that seen when 5% CO2 in 20% O2 was inhaled. Similar to other conditions, an increase in ambient temperature in hypoxic dogs resulted in a shift in the respiratory pattern to the left at most points along the curves. Discussion It is of considerable interest that some of these conscious dogs would pant at a cool ambient temperature of 20 “C despite the fact that the neutral temperature for dogs has been found to be 23-25 “C (Hammel et al., 1958). We do not believe that these animals, conditioned to the laboratory, were excited since they were allowed to adjust to the room for more than an hour before the study and without exception they were resting quietly. As evident from figs. 1 and 2, all dogs had relatively constant respiratory rates and minute ventilations in the control periods. Unlike the two conscious dogs studied by Thiele and Albers (1963) in which the respiratory rate was closely related to ambient temperature, other temperature regulatory factors must have been playing an important role in the ventilation of our group of dogs. It has been clearly demonstrated that central as well as peripheral receptor mechanisms affect thermoregulatory respiratory responses (Bligh, 1966 ; Hammel, 1968) and that these inputs affect the hypothalamic set-point for evaporative heat loss (Hellstrom and Hammel, 1967). In the control period breathing air (figs. 1 and 2), respiratory rates tended to be either less than 25 breaths per minute or greater than 100 breaths per minute. These different groupings of respiratory rate presumably relate to non-panting and panting dogs although Whittow (1966) has pointed out the lack of definitions for these terms. Some authors (Schmidt-Nielsen, 1964 ; Forster and Ferguson, 1952) have felt panting to take place at respiratory frequencies greater than 200 per minute, but Lim and Grodins (1955) arbitrarily defined panting in anaesthetized dogs as respiratory rates greater than 100 per minute. Hammouda (1933) observed that the Hering-Breuer reflex diminished in the anaesthetized dog with respiratory rates greater than 75 per minute and it was generally absent at respiratory rate above 120 breathes per minute. On this basis Hammouda (1933) defined the lower limits of panting as 120 breaths per minute. Panting in animals has been studied by many methods including the increasing of environmental temperature or by heating the hypothalamus. Measurements have frequently been taken during the transient periods where ventilation has been adjusting to the heat stimulus. This has led Schmidt-Nielsen (1964) to conclude that “the dog changes abruptly from resting respiration to panting, and that there are no intermediate rates of respiration”. However, a wide range of relatively constant respiratory rates are evident in figs. 1 and 2 so that dogs under constant environmental conditions can have “intermediate” levels of respiratory rate. It is well known that breathing through valves and the use of masks or endotracheal tubes will affect the pattern of respiration of animals (Albers, 1961a; Hales and Web-
88
D. B. JENNINGS
AND R. D. MACKLIN
ster, 1967) although intubation need not necessarily interfere with normal heat exchange (Wessel et a&, 1966). Such effects on respiratory pattern could be secondary to several mechanisms. Breathing throu~ an endotrach~l tube by modi~ing heat exchange from the pharyngeal region to the brain might result in a more constant hypothalamic temperature in our dogs and thus reduce some variability in ventilatory control. It has been demonstrated that normal panting in cats will produce a decrease in diencephalic temperature (Hunter and Adams, 1966) and similar changes in hypothalamic temperatures have been observed in resting dogs (Hammel et al., 1963). Such changes in hypotha~mic temperature during panting could affect respiratory the~oregulato~ mechanisms (Bligh, 1966; Hammel, 1968). Interference by the intubation with the normal role of the upper airways in regulating heat and water exchange by means of a temperature gradient (Schmidt-Nielsen et al., 19’70)may have affected the efficiency of the respiratory evaporative heat loss mechanism. Despite this, however, there was only a small increase in mean rectal temperature of the dogs from 38.5 “C&O.14 (S.E.M.) in the cool room to 39.0 “Ct_ 0.01 (S.E.M.) in the warm room and not all dogs panted in the warm room despite the ambient heat stress. In addition one would expect that respiratory rate would be slightly less than normal when respiratory airway resistance is increased by a valve system (Cain and Otis, 1948-49) and this may have accounted for the intermediate levels of respiratory rate which we observed. In spite of the high resistance valve, dogs attained respiratory rates approaching 300 breaths per minute and such frequencies approach the upper limit of respiratory rate generally recorded even in unhindered dogs. Thus, it is unlikely that the presence of the endotracheal tube had a major effect on the respiratory patterns observed. It is apparent from the sigmoidal relationship between respiratory rate and minute ventilation (fig. 7) in resting dogs breathing air at a cool ambient temperature, that as the dog begins to increase minute ventilation, the increase in respiratory rate is such that tidal volume becomes a minimum. With subsequent increases in minute ventilation, respiratory rate becomes relatively constant and increases in minute ventilation are associated with relatively small increases in tidal volume. We are unaware of anyone previously commenting on such a secondary increase in tidal volume while panting rate is maintained. Moreover, it is not apparent in the respiratory pattern of sheep in the “Phase I” response described by Hales and Webster (1967) nor in the respiratory pattern of pigs (Ingram and Legge, 1969170). Albers (1961d) calculated the theoretical pattern of respiratory rate and tidal volume in the dog for changing ventilations assuming no change in alveolar carbon dioxide tension. These calculations predicted a constantly increasing respiratory rate and no secondary increase in tidal volume. A decrease in tidal volume with thermally induced changes in ventilation has been observed previously in dogs, cattle, sheep and pigs (Hemmingway, 1938 ; Findlay, 1957, Albers, 1961a ; Halesand Webster, 1967 ; Ingram and Legge, 1969/70}. It has been noted that during prolonged intense heat stress that rapid shallow breathing becomes both
VENTILATORY
89
PATTERNS OF DOGS
RESPlRATOhY PATTERNS and ISOWLS of TIDAL VOLUME 300
1
250
1
200
RESPIRATORY RATE
150
(breaths/min.) 100
50
0 0
5
10
15
20
25
30
35
40
45
MINUTE VENTILATION (litres) Fig. 7. The heavy solid line depicts the pattern of respiratory rate and minute ventilation for resting dogs in a cool room and the dotted line represents the same parameters during exercise in the cool room. In the figure the isovols of tidal volume (ml) are shown in relation to the respiratory patterns.
slower and deeper (Hales and Webster, 1967 ; Findlay and Hales, 1969; Hales and Bligh, 1969). However, such a change in respiratory pattern during heat was not observed for the degree of temperature stress in our warm room studies. In every instance where there was a change in respiratory pattern in the warm room in our dogs, the pattern of respiratory rate shifted to the left (figs. 4-6) and there was therefore only an associated decrease in tidal volume. Unlike heat which shifted the pattern of respiratory rate to the left, hypoxia, hypercapnia and exercise shifted the pattern of respiratory rate to the right (figs. 4-7) so that every level of minute ventilation was associated with a greater tidal volume. This effect of asphyxia or hypercapnia in decreasing respiratory rate in tachypnoeic dogs has been previously observed by Richet (1898), Anrep and Hammouda (1932) and Albers (1961~) but has not been described in detail in relation to minute ventilation. Anrep and Hammouda (1932) did not find an effect of hypoxia on respiratory rate of anaesthetized dogs which is similar to our findings for conscious dogs studied in a warm room (fig. 2). The likely effect of ventilating with a great tidal volume would be to increase alveolar ventilation for every level of minute ventilation and this could be useful in the presence of hypoxia or hypercapnia and during exercise. In addition to the effects of changes of respiratory pattern on heat exchange and gas exchange, changes in frequency and depth can affect the work of breathing. Although Whittow and Findlay (1968) have shown that cattle can pant without altering their oxygen consumption, there is some question as to the efficiency of panting in
90
D. B. JENNINGS AND R. D. MACKLIN
dogs (Albers, 1961b ; Spaich et at., 1968). The calculations for dogs, however, are based primarily on data obtained from anaesthetized animals and it is possible that the most efficient patterns of respiratory rate and depth are altered by anaesthesia. Crawford (1962) has determined that the resonant frequency of the dog’s respiratory system is 5.28 cycles per sec. Thus, at that level of respiratory rate - 320 breaths per minute - respiratory impedance would be minimal and the work of breathing should require least effort. However, Mead (1960) has shown that there is a different frequency at which the average force of the respiratory muscles is at a minimum. Mead (1960) has also commented on the fact that respiratory rate can change over a rather wide range with relatively little change in either respiratory work or muscle force. The ventilatory responses of individual dogs breathing various comb~ations of oxygen and carbon dioxide can be extremely different although they do in fact fit into more general and predictable respiratory patterns. These patterns of respiration probably represent optimization of respiratory thermoregulation, alveolar ventilation and the work of breathing. The complexities of these ventilatory responses to different stimuli provide another example of the multifactorial nature of the regulation of respiration and clearly illustrate the difficulties that are associated with studies of conscious dogs. Acknowledgements The authors wish to express their appreciation to Drs. J. D. Hatcher and C. IL Chapler for their helpful criticism of the manuscript. The excellent technical assistance of Mrs.M~y Dean, Mr. Geoff Pierson and Mrs. Anne Marie Newcombe is gratefully acknowledged. References Albers, C. (1961a). Der Mechanismus des Warmehechelns beim Hund. I. Die Ventilation und die arteriellen Blutgase wlhrend des Wlrmehechelns. Pfliigers Arch. ges. Physiol. 274: 125-147. Albers, C. (1961b). Der Mechanismus des Warmehechelns beim Hund. II. Der respiratorische Stoffwechsel wlhrend des wrmehechelns. Pjliigers Arch. ges. Physiol. 274 : 148-165. Albers, C. (1961c). Der Mechanismus des Wlrmehechelns beim Hund. HI. Die CO,-Empfindlichkeit des Atemxentrums wghrend des WZrmehechelns. Pftigers Arch. ges. Pf2ysiol. 274: 166-183. Albers, C. (1961df. Der Mechanismus des WIrmehecheins beim Hund. IV. Die Wechsel~rkung zwischen Blut~sreg~ation und Tem~atu~egulation. ~~~~s Arch. ges. Physiol. 274: 184-191. Anrep, G. V. and M. Hammouda (1932). Observations on panting. J. Phys~o~.(~~0~) 77 : 16-34. Bligh, J. (1966). The thermosensitivity of the hypothalamus and thermoregulation in mammals. Bill. Rev. 41: 317-367. Cain, C. and A. B. Otis (194-g). Some physiological effects resulting from added resistance to respiration. J. At&t. Med. 19: 149-160. Crawford, E. C., Jr. (1962). Mechanical aspects of panting in dogs. J. Appl. Physiol. 17: 249-251. Findlay, J. D. (1957). The respiratory activity of calves subjected to thermal stress. J. Physiol. (London) 136 : 300-309.
Findlay, J. D. and J. R. S. Hales (1969). Hypothalamic temperature and the regulation of respiration of the ox exposed to severe heat. J. Physiof. (London) 203 : 651663. Forster, R. E and T. B. Ferguson (1952). Relationship between hypothalamic temperature and thermoregulatory effecters in unanaesthetized cats. Am. J. Physiol. 169: 255-269.
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PATTERNS OF DOGS
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Hales, J. R. S. and M. E. D. Webster (1967). Respiratory function during thermal tachypnoea in sheep. J. Physiol. (London) 190: 241-260. Hales, J. R. S. and J. Bligh (1969).Respiratory responses ofthe conscious dog to severe heat stress. Experientia 25: 818-819. Hammel, H. T., C. H. Wyndham and J. D. Hardy (1958). Heat production and heat loss in the dog at 8-36 ‘C environmental temperature. Am. J. Physiol. 197 : 99-108. Hammel, H. T., D. C. Jackson, J. A. J. Stolwijk, J. D. Hardy and S. B. Stromme (1963). Temperature regulation by hypothalamic proportional control with an adjustable set point. J. Appl. Physiol. 18 : 11461154. Hammel, H. T. (1968). Regulation of internal body temperature. Ann. Rev. Physiol. 30: 641-710. Hammouda, M. (1933). The central and reflex mechanism of panting. J. Physiol. (London) 77: 319-336. Hellstrom, B. and H. T. Hammel (1967). Some characteristics of temperature regulation in the unanaesthetized dog. Am. J. Physiol. 213: 547-556. Hemmingway, A. (1938). The panting response of normal unanaesthetized dogs to measured dosages of diathemy heat. Am. J. Physiol. 121: 747-754. Hey, E. N., B. B. Lloyd, D. J. C. Cunningham, M. G. M. Jukes and D. P. G. Bolton (1966). Effects of respiratory stimuli on the depth and frequency of breathing in man. Respir. Physiol. 1: 193205. Hunter, W. S. and T. Adams (1966). Respiratory heat exchange influences on diencephalic temperature in the cat. J. Appt. Physiol. 21: 873-876. Ingram, D. L. and K. F. Legge (1969/70). The effect of environmental temperature on respiratory ventilation in the pig. Respir. Physiol. 8: 1-12. Lim, P. K. and F. S. Grodins (1955). Control of thermal panting. Am. J. Physiol. 180: 44S449. Mead, J. (1960). Control of respiratory frequency. J. Appl. Physiol. 15: 325-336. Richet, C. (1898). Dictionnaire de Physiologie. Paris, 3 : 175191. Schmidt-Nielsen, K. (1964). Carnivores. In : Desert Animals, Physiological Problems of Heat and Water. Oxford University Press, p. 108. Schmidt-Nielsen, K., F. R. Hainsworth and D. E. Murresh (1970). Counter-current heat exchange in the respiratory passages. Respir. Physiol. 9 : 263-276. Spaich, P., W. Usinger and C. Albers (1968). Oxygen cost of panting in anaesthetized dogs. Respir. Physiol. 5 : 302-314. Thiele, P. and C. Albers (1963). Die Wasserdampfabgabe durch die Atemwege und der Wirkungsgrad des Warmehechelns beim wachen Hund. PjXgers Arch. ges. Physiol. 278 : 316324. Thilenius, 0. G. and C. B. Vial (1963). Chronic tracheostomy in dogs. J. Appl. Physiol. 18: 439440. Wessel, H. U., G. W. James and M. H. Paul (1966). Effects of respiration and circulation on central blood temperature of the dog. Am. .I. Physiol. 211: 1403-1412. Whittow, G. C. (1966). Terminology of thermoregulation. Physiologist 9: 358-360. Whittow, G. C. and J. D. Findlay (1968). Oxygen cost of thermal panting. Am. J. Physiol. 214: 94-99.
THJI EFFECTS OF Oz AND CO2 AND OF AMJHENT TEMPERATUREl ON VENTILATORY PATTERNS OF DOGS’
D. B. JENNINGS*
and R. D. MACKLIN
Department of Physiology, Queen’s University, Kingston, Ontario, Canada
Abetract, Interrelationships between minute ventilation and respiratory rate were examined in conscious dogs at rest and during exercise. Studies were carried out at both cool (19-23 “C) and warm (27-32 “C) ambient temperatures while the dogs breathed room air or different mixtures of O2 and COz. The relation between respiratory rate and minute v~t~tion in a cool room was sigmoidal with a mean respiratory rate of 15 breaths per minute when the mean ventilation was 2.9 L per minute and with a mean respiratory rate of 276 breaths per minute when the mean ventilation was 27.5 L per minute. This fundamental sigmoidal relation in the cool room was shifted to the right slightly by breathing 10 ‘A0, or by light exercise and more markedly by breathing 5 % COs. In a warm room the patterns established in the cool room were shifted to the left. The respiratory response of the animals to a change in the inspired oxygen or carbon dioxide mixture was shown to depend on the initial frequency-ventilation relation. Breathing pattern Control of breathing Dogs
Hypercapnia Hypoxia Thermal polypnoea
Human subjects have a fixed relationship between minute ventilation and respiratory rate for quite a number of stimuli except for increased body temperature where respiratory rate is increased for a given minute ventilation (Hey et al., 1966). In contrast, in the conscious dog, which pants with frequencies up to 300-400 breaths per minute (Sc~dt-Niel~n, 1964), Richet (1898) noted that asphyxia or carbon dioxide prevented tachypnoea. Anrep and Hammouda (1932) also noted that in panting anaesthetized dogs, the inhalation of carbon dioxide caused a decrease in respiratory rate, whereas, anoxia was found to have no effect on respiratory rate. We have found that some conscious resting dogs acclimated to an ambient temperature of 20 “C and by many criteria in a steady state panted consistently despite the Accepted for publication 15 April 1972. ’ Supported by grants to D. B. Jennings from the Defence Research Board of Canada and the Ontario Heart Foundation. 2 Senior Research Fellow, Canadian Heart Foundation (1964-1970).
79
80
D. B. JENNINGS
AND R. D. MACKLIN
cool temperature. Other dogs exposed to the same conditions breathed at low ventilations and low respiratory rates. Still other animals panted in some studies but on other days were non-panters. Analysis of respiration in these dogs breathing air indicated a predictable continuous pattern of respiratory rate with respect to minute ventilation. When these dogs were subjected to stimuli such as increased ambient temperature, exercise, hypercapnia or hypoxia there were significant changes in the patterns of respiratory rate and minute ventilation. Methods Seven male mongrel dogs, 19-29 kg body weight, were prepared with chronic tracheostomies (Thilenius and Vial, 1963). In the studies an endotracheal tube with an inflatable cuff was placed in the trachea and connected to an Ambu two-way valve. The inspiratory resistance of the valve was 2 cm of water/L/set and expiratory resistance was 4 cm of water/L/set. The dead space of the endotracheal tube plus the Ambu valve was 26 ml. The dogs inspired either room air or a gas mixture from a large balloon at ambient pressure. Expired gas was collected in a Tissot spirometer and the minute ventilation (BTPS) determined. Respiratory rate was determined from expiratory air flow monitored with a Fleisch pneumotach and a Statham PM15 or a Pace P7 differential transducer. STUDIES
IN DOGS AT REST
Four groups of resting studies were carried out in each of the seven dogs between June and September over a 2 year period. Two different ranges of laboratory temperature were provided for the experiment : a. a cool room with a temperature range of 19-23 “C and b. a warm room with a temperature range of 27-32 “C. The dogs were brought to the laboratory at least one hour prior to the experiment, the endotracheal tube introduced, and the other adjustments for measurements made. Then the dog was allowed to sit or lie quietly on a treadmill. When the experiment was started, the animal was monitored for at least 10 min while breathing room air and then for two successive 10-15 minute periods while breathing: a. a mixture of 10% oxygen! followed by 10% oxygen + 5% carbon dioxide ; followed by room air, or b. 5% carbon dioxide in air ; followed by 5% carbon dioxide in 80% oxygen ; followed by room air. In each experiment the minute to minute changes in minute ventilation and respiratory rate were determined. STUDIES
IN DOGS DURING
EXERCISE
At the cool ambient temperature, measurements of respiratory rate and minute ventilation were made in 6 of the 7 animals while they walked at 1 mph on the treadmill. In all exercise experiments the dogs breathed room air for the first 30 min and measurements were made at lo,20 and 30 min. The experiment then took two forms :
VENTILATORY
81
PATTERNS OF DOGS
in 9 experiments the 6 animals continued to breathe room air ; whereas, in 13 experiments the animals were switched to inhale 5% CO, in air. In this second part of the experiment, respiratory measurements were made for up to 60 min at 5-10 minute intervals. ResuIts I. RESPIRATORY RATE IN DOGS BREATHING AND CARBON DIOXIDE (figs. 1 and 2)
THE VARIOUS
RESTING
COOL
MIXTURES
OF OXYGEN
DOGS
ROOM
ooa#l
x
#3*
#“:: 300
#6A #70 #SO
2oc
~P~AT~Y RATE 1oc
breaths/min.
( WARM
ROOM
Fig. 1. The minute to minute variations in respiratory rate iu dogs breathing room air, followed oy 5% COz in air (20% 0,), followed by 5% COz with 80% 0,, followed by room air. The same dogs were studied in both a cool room and a warm room.
82
D. B. JENNINGS AND R. D. MACKLIN
RESTING
DOGS
COOL
ROOM
Dog#l
x #3*
RESPIRATORY RATE
breatk/min.
1oG
o WARM
ROOM
1ocI-
0
AIR -10
-5
1
AIR 0
5
10
15
TIME
5
10
15
5
IO
15
20
25
I 30
(minutes)
Fig. 2. The minute to minute variations in respiratory r&e in dogs breathing room air followed by 10% oxygen, followed by 10% 0, with 5% COz, followed by room air in both a cool room and a warm room.
In the first columns of figs. 1 and 2, the respiratory rates of dogs breathing room air at cool and warm ambient conditions are plotted for the 10 min preceding breathing the different gas mixtures. In general when breathing room air, a non-panting dog (respiratory rate < 100 breaths per minute) had very little variation in respiratory rate whereas a panting dog (respiratory rate > 100 breaths per minute) had a much more variable respiratory rate per minute. However, the variation in respiratory frequency seen in tachypnoeic animals was confined within a range and it was unusual to see an animal that was breathing rapidly suddenly breathe slowly. In fig. 1, it can be seen that panting dogs had a decrease in respiratory rate when
VENTILATORY
PATTERNS OF DOGS
83
breathing 5% COz in both cool and ,warm rooms. When the oxygen level was increased from 20% to 80% O2 in the 5% CO, mixture there was no apparent effect of the high oxygen level on the respiratory rate. When 10% oxygen was breathed in a cool room (fig. 2) panting dogs responded by a slight decrease in respiratory rate. However, in the warm room, a similar decrease in respiratory rate in panting dogs was not observed when breathing 10% oxygen (fig. 2). In both the cool and warm rooms, the addition of 5 % CO* to the 10% oxygen resulted in a comparable marked decrease in respiratory rate in panting dogs. Slowly breathing dogs, as shown in both figs. 1 and 2, generally had relatively small and variable increases in respiratory rate with hypoxia or hypercapnia. In panting dogs, the responses as described indicate an order or priority for stimuli in determin~g the degree of tachypnoea. Hypercapnia was an overriding stimulus since it depressed respiratory rate in the warm as well as the cool room. Thermal stress was second in importance since tachypnoea appeared to be maintained in the warm room during the same anoxic stimulus which had lowered respiratory rate in the cool room. Thirdly, anoxia depressed respiratory rate in the panting dogs in the cool room. II. VENTILATORY (figs. 3a, b, and c)
RESPONSES
OF INDIVIDUAL
DOGS TO VARIOUS
GAS MIXTURES
The most striking finding was the enormous variability in the ventilatory patterns between dogs breathing the same gas mixtures. In this section we will examine two examples, figs. 3a and 3b, where the dogs breathed with entirely diierent patterns. Then we will describe the ventilatory pattern of another dog (fig. 3~)which, within the course of a study, switched from pattern type 3a to pattern type 3b. In these examples, minute to minute observations of minute ventilation with relation to respiratory rate are plotted for conditions where the dogs breathed room air, 10% 02, and 10% 0, with 5% CO, in a cool room. The proportions of the axis in all three plots are the same and in fig. 3a, the areas of observations contained in fig. 3b and 3c are outlined. Within each figure an arrow joins the last minute of breathing a given gas mixture with the first minute of breathing another gas mixture. In some cases additional arrows show the change in pattern with time during the breathing of a gas mixture. Figure 3a shows a dog that was breathing with a high respiratory rate approaching 300 breaths per minute on room air. When switched to 10% 0, the animal had minimal changes in minute ventilation but any given ventilation was attained at a lower respiratory rate. When breathing 10% O2 with 5% COz the animal increased ventilation but with a marked reduction in respiratory rate. Figure 3b depicts the ventilatory pattern changes in a dog breathing at a low respiratory rate in room air. When this animal breathed 10% 0, an initial increase in minute ventilation and respiratory rate was followed by a return towards control. When 5% CO2 was breathed with 10% O2 an increased ventilation was accomplish~ with smaller increases in respiratory rate at any given ventilation than seen with the 10% 0, alone.
(a)
Cool Room
Dog 88
84
RESPIRATORY RATE
*OO-
( breaths / min.1 ,oo_ ---/-
3_B
( litres /minute
VENTILATION
1
Cool Room
(b)
RESPIRATORY RATE
b
(4
lb VENTILATION
% ( litres /minute I
sb
d3
Cool Room
Dow3
a-ROOMAIR *
IO?+
Y wxq+5r.cq
RESPIRATORY RATE ereatw/mkb)
4
rb
&a
VENTILATION
bb
4ki
(I/min.f
Figs. 3a, b, c. Plots of respiratory rate versus minute ventilation with the symbols representing minute to minute pairs of data. The last minute of breathing a given mixture is joined to the first and in some cases subsequent minutes of breathing a different gas mixture. The examples are from three different dogs with different resting respiratory rates when breathing room ah in a cool room. Figures 3a and 3b demonstrate the marked differences in response between dogs which are slowly breathing and dogs which are tachypnoeic Figure 3c demonstrates that a dog can shift during the course of a study from breathing rapidly to breathing slowly and therefore can change from the pattern of 3a into the pattern of 3b. The areas covered by graphs 3b and 3c are shown on graph 3a.
VENTILATORY
PATTERNS OF DOGS
85
In fig. 36, a dog, which started out on air breathing at a high respiratory rate like example 3a, went through changes of pattern breathing 10% O2 and 10% O2 with 5% COz that were in-between examples 3a and 3b. Finally, during recovery on room air this dog breathed slowly as in 3b. Thus, this animal shifted from panting to nonpanting during these ventilatory stimuli. III. COMPOSITE VENTILATORY PATTERNS IN DOGS BREATHING DIFFERENT GAS MIXTURES AT REST UNDER DIFFERENT AMBIENT TEMPERATURES AND DURING EXERCISE (tigs. 4, 5, 6)
Despite the enormous variability between the breathing patterns of different dogs and even within some dogs, a unifying concept emerged when the data for all seven dogs were compiled. The mean respiratory rate was analyzed for 5 L ranges of minute ventilation. In figs. 4,5 and 6 respiratory rate per minute + 95% confidence limits is plotted against the mean minute ventilation. The small numbers beside the points indicate the number of observations analyzed at each point. Lines of best fit, drawn by eye, join the points repre~ntative of an in~vid~l set of conditions. Figure 4 represents the patterns of respiratory rate for minute ventilation in dogs breathing room air both at rest in a cool or warm room and while exercising in a cool room. The striking finding is the difference in respiratory pattern with respect to minute ventilation with a change in ambient temperature or with exercise. At rest in a cool room the respiratory rate rises rapidly between ventilations of 2.9 L per minute and 23 L per minute and then there is a relatively small change in frequency for further increases in minute ventilation. A thermal stress at rest shifts the pattern to the left INSPIRED GAS-ROOM
t
RESl,W+RM ROOM 0 REST,COOL ROOM 0 EXERCiSE.COOL -
AIR
300,
2
RESPIRATORY RATE breaths / min.1
204
100
+95% confiie
limits
300
50
~
VENTILATION
( litres/
minute
)
Fig. 4. Compiled data for 7 resting dogs breathing room air at rest in a cool room (e) and a warm room (*) and duringexercise in a cool room (0). The mean respiratory rates f 95% confidence limits were determined for 5 L ranges of minute ventilation. The number of pairs of data used in calculating each point is listed beside the symbol.
D. B. JENNINGS AND R. D. MACKLIN
Fig. 5. Compiled data for 7 dogs breathing room air at rest in a cool room (0) and breathing 5% CO, in air at rest in a cool room (A), 5% CO, in air at rest in a warm room (0) and during exercise in a cool room (I-J). The conventions used are the same as in fig. 4.
RESPIRATORY RATE breaths /min. ?95% confidence
limits
“d
4
Ib
b
h
rb VENTIl_ATIt$U
*
48
@a
c4
80
(titroa/mkte)
Fig. 6. Compiled data for 7 resting dogs breathing room air in a cool room (a), breathing 10% in both cool (0) and warm (*) rooms, and breathing 10% O2 with 5% CO2 in both cool (0) and warm (A) rooms. The conventions used are the same as in fig. 4.
over the lower range of ventilation. During exercise in a cool room the pattern is shifted to the right. Figure 5 depicts the effects of hypercapnia on the resting pattern. Five per cent CO2 in air causes a marked shift in the pattern to the right in resting dogs. The hypercapnic respiratory pattern is not affected by exercise but is shifted to the left by an increase in ambient temperature. The effects of hypoxia on the respiratory pattern are shown in fig. 6. A decrease in inspired O2 to 10% resulted in a small shift in the pattern to the right. When 10%
b¶
VENTILATORY
PATTERNS OF DOGS
87
O2 and 5% CO2 was inhaled, the effect of the carbon dioxide was to again cause a shift in the curve to the right almost identical to that seen when 5% CO2 in 20% O2 was inhaled. Similar to other conditions, an increase in ambient temperature in hypoxic dogs resulted in a shift in the respiratory pattern to the left at most points along the curves. Discussion It is of considerable interest that some of these conscious dogs would pant at a cool ambient temperature of 20 “C despite the fact that the neutral temperature for dogs has been found to be 23-25 “C (Hammel et al., 1958). We do not believe that these animals, conditioned to the laboratory, were excited since they were allowed to adjust to the room for more than an hour before the study and without exception they were resting quietly. As evident from figs. 1 and 2, all dogs had relatively constant respiratory rates and minute ventilations in the control periods. Unlike the two conscious dogs studied by Thiele and Albers (1963) in which the respiratory rate was closely related to ambient temperature, other temperature regulatory factors must have been playing an important role in the ventilation of our group of dogs. It has been clearly demonstrated that central as well as peripheral receptor mechanisms affect thermoregulatory respiratory responses (Bligh, 1966 ; Hammel, 1968) and that these inputs affect the hypothalamic set-point for evaporative heat loss (Hellstrom and Hammel, 1967). In the control period breathing air (figs. 1 and 2), respiratory rates tended to be either less than 25 breaths per minute or greater than 100 breaths per minute. These different groupings of respiratory rate presumably relate to non-panting and panting dogs although Whittow (1966) has pointed out the lack of definitions for these terms. Some authors (Schmidt-Nielsen, 1964 ; Forster and Ferguson, 1952) have felt panting to take place at respiratory frequencies greater than 200 per minute, but Lim and Grodins (1955) arbitrarily defined panting in anaesthetized dogs as respiratory rates greater than 100 per minute. Hammouda (1933) observed that the Hering-Breuer reflex diminished in the anaesthetized dog with respiratory rates greater than 75 per minute and it was generally absent at respiratory rate above 120 breathes per minute. On this basis Hammouda (1933) defined the lower limits of panting as 120 breaths per minute. Panting in animals has been studied by many methods including the increasing of environmental temperature or by heating the hypothalamus. Measurements have frequently been taken during the transient periods where ventilation has been adjusting to the heat stimulus. This has led Schmidt-Nielsen (1964) to conclude that “the dog changes abruptly from resting respiration to panting, and that there are no intermediate rates of respiration”. However, a wide range of relatively constant respiratory rates are evident in figs. 1 and 2 so that dogs under constant environmental conditions can have “intermediate” levels of respiratory rate. It is well known that breathing through valves and the use of masks or endotracheal tubes will affect the pattern of respiration of animals (Albers, 1961a; Hales and Web-
88
D. B. JENNINGS
AND R. D. MACKLIN
ster, 1967) although intubation need not necessarily interfere with normal heat exchange (Wessel et a&, 1966). Such effects on respiratory pattern could be secondary to several mechanisms. Breathing throu~ an endotrach~l tube by modi~ing heat exchange from the pharyngeal region to the brain might result in a more constant hypothalamic temperature in our dogs and thus reduce some variability in ventilatory control. It has been demonstrated that normal panting in cats will produce a decrease in diencephalic temperature (Hunter and Adams, 1966) and similar changes in hypothalamic temperatures have been observed in resting dogs (Hammel et al., 1963). Such changes in hypotha~mic temperature during panting could affect respiratory the~oregulato~ mechanisms (Bligh, 1966; Hammel, 1968). Interference by the intubation with the normal role of the upper airways in regulating heat and water exchange by means of a temperature gradient (Schmidt-Nielsen et al., 19’70)may have affected the efficiency of the respiratory evaporative heat loss mechanism. Despite this, however, there was only a small increase in mean rectal temperature of the dogs from 38.5 “C&O.14 (S.E.M.) in the cool room to 39.0 “Ct_ 0.01 (S.E.M.) in the warm room and not all dogs panted in the warm room despite the ambient heat stress. In addition one would expect that respiratory rate would be slightly less than normal when respiratory airway resistance is increased by a valve system (Cain and Otis, 1948-49) and this may have accounted for the intermediate levels of respiratory rate which we observed. In spite of the high resistance valve, dogs attained respiratory rates approaching 300 breaths per minute and such frequencies approach the upper limit of respiratory rate generally recorded even in unhindered dogs. Thus, it is unlikely that the presence of the endotracheal tube had a major effect on the respiratory patterns observed. It is apparent from the sigmoidal relationship between respiratory rate and minute ventilation (fig. 7) in resting dogs breathing air at a cool ambient temperature, that as the dog begins to increase minute ventilation, the increase in respiratory rate is such that tidal volume becomes a minimum. With subsequent increases in minute ventilation, respiratory rate becomes relatively constant and increases in minute ventilation are associated with relatively small increases in tidal volume. We are unaware of anyone previously commenting on such a secondary increase in tidal volume while panting rate is maintained. Moreover, it is not apparent in the respiratory pattern of sheep in the “Phase I” response described by Hales and Webster (1967) nor in the respiratory pattern of pigs (Ingram and Legge, 1969170). Albers (1961d) calculated the theoretical pattern of respiratory rate and tidal volume in the dog for changing ventilations assuming no change in alveolar carbon dioxide tension. These calculations predicted a constantly increasing respiratory rate and no secondary increase in tidal volume. A decrease in tidal volume with thermally induced changes in ventilation has been observed previously in dogs, cattle, sheep and pigs (Hemmingway, 1938 ; Findlay, 1957, Albers, 1961a ; Halesand Webster, 1967 ; Ingram and Legge, 1969/70}. It has been noted that during prolonged intense heat stress that rapid shallow breathing becomes both
VENTILATORY
89
PATTERNS OF DOGS
RESPlRATOhY PATTERNS and ISOWLS of TIDAL VOLUME 300
1
250
1
200
RESPIRATORY RATE
150
(breaths/min.) 100
50
0 0
5
10
15
20
25
30
35
40
45
MINUTE VENTILATION (litres) Fig. 7. The heavy solid line depicts the pattern of respiratory rate and minute ventilation for resting dogs in a cool room and the dotted line represents the same parameters during exercise in the cool room. In the figure the isovols of tidal volume (ml) are shown in relation to the respiratory patterns.
slower and deeper (Hales and Webster, 1967 ; Findlay and Hales, 1969; Hales and Bligh, 1969). However, such a change in respiratory pattern during heat was not observed for the degree of temperature stress in our warm room studies. In every instance where there was a change in respiratory pattern in the warm room in our dogs, the pattern of respiratory rate shifted to the left (figs. 4-6) and there was therefore only an associated decrease in tidal volume. Unlike heat which shifted the pattern of respiratory rate to the left, hypoxia, hypercapnia and exercise shifted the pattern of respiratory rate to the right (figs. 4-7) so that every level of minute ventilation was associated with a greater tidal volume. This effect of asphyxia or hypercapnia in decreasing respiratory rate in tachypnoeic dogs has been previously observed by Richet (1898), Anrep and Hammouda (1932) and Albers (1961~) but has not been described in detail in relation to minute ventilation. Anrep and Hammouda (1932) did not find an effect of hypoxia on respiratory rate of anaesthetized dogs which is similar to our findings for conscious dogs studied in a warm room (fig. 2). The likely effect of ventilating with a great tidal volume would be to increase alveolar ventilation for every level of minute ventilation and this could be useful in the presence of hypoxia or hypercapnia and during exercise. In addition to the effects of changes of respiratory pattern on heat exchange and gas exchange, changes in frequency and depth can affect the work of breathing. Although Whittow and Findlay (1968) have shown that cattle can pant without altering their oxygen consumption, there is some question as to the efficiency of panting in
90
D. B. JENNINGS AND R. D. MACKLIN
dogs (Albers, 1961b ; Spaich et at., 1968). The calculations for dogs, however, are based primarily on data obtained from anaesthetized animals and it is possible that the most efficient patterns of respiratory rate and depth are altered by anaesthesia. Crawford (1962) has determined that the resonant frequency of the dog’s respiratory system is 5.28 cycles per sec. Thus, at that level of respiratory rate - 320 breaths per minute - respiratory impedance would be minimal and the work of breathing should require least effort. However, Mead (1960) has shown that there is a different frequency at which the average force of the respiratory muscles is at a minimum. Mead (1960) has also commented on the fact that respiratory rate can change over a rather wide range with relatively little change in either respiratory work or muscle force. The ventilatory responses of individual dogs breathing various comb~ations of oxygen and carbon dioxide can be extremely different although they do in fact fit into more general and predictable respiratory patterns. These patterns of respiration probably represent optimization of respiratory thermoregulation, alveolar ventilation and the work of breathing. The complexities of these ventilatory responses to different stimuli provide another example of the multifactorial nature of the regulation of respiration and clearly illustrate the difficulties that are associated with studies of conscious dogs. Acknowledgements The authors wish to express their appreciation to Drs. J. D. Hatcher and C. IL Chapler for their helpful criticism of the manuscript. The excellent technical assistance of Mrs.M~y Dean, Mr. Geoff Pierson and Mrs. Anne Marie Newcombe is gratefully acknowledged. References Albers, C. (1961a). Der Mechanismus des Warmehechelns beim Hund. I. Die Ventilation und die arteriellen Blutgase wlhrend des Wlrmehechelns. Pfliigers Arch. ges. Physiol. 274: 125-147. Albers, C. (1961b). Der Mechanismus des Warmehechelns beim Hund. II. Der respiratorische Stoffwechsel wlhrend des wrmehechelns. Pjliigers Arch. ges. Physiol. 274 : 148-165. Albers, C. (1961c). Der Mechanismus des Wlrmehechelns beim Hund. HI. Die CO,-Empfindlichkeit des Atemxentrums wghrend des WZrmehechelns. Pftigers Arch. ges. Pf2ysiol. 274: 166-183. Albers, C. (1961df. Der Mechanismus des WIrmehecheins beim Hund. IV. Die Wechsel~rkung zwischen Blut~sreg~ation und Tem~atu~egulation. ~~~~s Arch. ges. Physiol. 274: 184-191. Anrep, G. V. and M. Hammouda (1932). Observations on panting. J. Phys~o~.(~~0~) 77 : 16-34. Bligh, J. (1966). The thermosensitivity of the hypothalamus and thermoregulation in mammals. Bill. Rev. 41: 317-367. Cain, C. and A. B. Otis (194-g). Some physiological effects resulting from added resistance to respiration. J. At&t. Med. 19: 149-160. Crawford, E. C., Jr. (1962). Mechanical aspects of panting in dogs. J. Appl. Physiol. 17: 249-251. Findlay, J. D. (1957). The respiratory activity of calves subjected to thermal stress. J. Physiol. (London) 136 : 300-309.
Findlay, J. D. and J. R. S. Hales (1969). Hypothalamic temperature and the regulation of respiration of the ox exposed to severe heat. J. Physiof. (London) 203 : 651663. Forster, R. E and T. B. Ferguson (1952). Relationship between hypothalamic temperature and thermoregulatory effecters in unanaesthetized cats. Am. J. Physiol. 169: 255-269.
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PATTERNS OF DOGS
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Hales, J. R. S. and M. E. D. Webster (1967). Respiratory function during thermal tachypnoea in sheep. J. Physiol. (London) 190: 241-260. Hales, J. R. S. and J. Bligh (1969).Respiratory responses ofthe conscious dog to severe heat stress. Experientia 25: 818-819. Hammel, H. T., C. H. Wyndham and J. D. Hardy (1958). Heat production and heat loss in the dog at 8-36 ‘C environmental temperature. Am. J. Physiol. 197 : 99-108. Hammel, H. T., D. C. Jackson, J. A. J. Stolwijk, J. D. Hardy and S. B. Stromme (1963). Temperature regulation by hypothalamic proportional control with an adjustable set point. J. Appl. Physiol. 18 : 11461154. Hammel, H. T. (1968). Regulation of internal body temperature. Ann. Rev. Physiol. 30: 641-710. Hammouda, M. (1933). The central and reflex mechanism of panting. J. Physiol. (London) 77: 319-336. Hellstrom, B. and H. T. Hammel (1967). Some characteristics of temperature regulation in the unanaesthetized dog. Am. J. Physiol. 213: 547-556. Hemmingway, A. (1938). The panting response of normal unanaesthetized dogs to measured dosages of diathemy heat. Am. J. Physiol. 121: 747-754. Hey, E. N., B. B. Lloyd, D. J. C. Cunningham, M. G. M. Jukes and D. P. G. Bolton (1966). Effects of respiratory stimuli on the depth and frequency of breathing in man. Respir. Physiol. 1: 193205. Hunter, W. S. and T. Adams (1966). Respiratory heat exchange influences on diencephalic temperature in the cat. J. Appt. Physiol. 21: 873-876. Ingram, D. L. and K. F. Legge (1969/70). The effect of environmental temperature on respiratory ventilation in the pig. Respir. Physiol. 8: 1-12. Lim, P. K. and F. S. Grodins (1955). Control of thermal panting. Am. J. Physiol. 180: 44S449. Mead, J. (1960). Control of respiratory frequency. J. Appl. Physiol. 15: 325-336. Richet, C. (1898). Dictionnaire de Physiologie. Paris, 3 : 175191. Schmidt-Nielsen, K. (1964). Carnivores. In : Desert Animals, Physiological Problems of Heat and Water. Oxford University Press, p. 108. Schmidt-Nielsen, K., F. R. Hainsworth and D. E. Murresh (1970). Counter-current heat exchange in the respiratory passages. Respir. Physiol. 9 : 263-276. Spaich, P., W. Usinger and C. Albers (1968). Oxygen cost of panting in anaesthetized dogs. Respir. Physiol. 5 : 302-314. Thiele, P. and C. Albers (1963). Die Wasserdampfabgabe durch die Atemwege und der Wirkungsgrad des Warmehechelns beim wachen Hund. PjXgers Arch. ges. Physiol. 278 : 316324. Thilenius, 0. G. and C. B. Vial (1963). Chronic tracheostomy in dogs. J. Appl. Physiol. 18: 439440. Wessel, H. U., G. W. James and M. H. Paul (1966). Effects of respiration and circulation on central blood temperature of the dog. Am. .I. Physiol. 211: 1403-1412. Whittow, G. C. (1966). Terminology of thermoregulation. Physiologist 9: 358-360. Whittow, G. C. and J. D. Findlay (1968). Oxygen cost of thermal panting. Am. J. Physiol. 214: 94-99.