variation of heart rate in the California sea Zion. Am. J. Physiol. 222(2) : 260-264. 1972.-The respiratory variation of heart rate was studied in the lightly restrained ...
AMERICAN
JOURNAL
OF PHYSIOLOGY 1972. Printed
Vol. 222, No. 2, February
in U.S.A.
Respiratory
variation
heart
of
rate in the California
sea lion
Y.-C. LIN, D. T. MATSUURA, AND G. C. WHITTOW Department of Physiology, University of Hawaii School of Medicine,
LIN, Y.-C., D. T. MATSUURA, AND G. C. WHITTOW. Respiratory variation of heart rate in the California sea Zion. Am. J. Physiol. 222(2) : 260-264. 1972.-The respiratory variation of heart rate was studied in the lightly restrained but unanesthetized California sea lion. The respiratory cycle of the California sea lion consists of a rapid expiration and inspiration, in succession, followed by a long period of apnea until the next expiration. The apnea accounts for 84% of the respiratory cycle. A tachycardia occurred, on the average, 0.25 set after the onset of inspiration. The heart slowed down on completion of inspiration, and remained at a low level throughout the apneic and expiratory phases of the normal respiratory cycle. The lowest level of heart rate during a normal respiratory cycle was comparable to that of experimental diving. The normal heart rate of the California sea lion is represented by a low level for 84% of the time and for the remaining period is at a high level, approximately twice that during the apneic and expiratory period of the respiratory cycle. Since the lag between the start of inspiration and the increase in heart rate was negligible, it is reasoned that a central control mediated by the vagus nerves, as deduced from atropine experiments, was involved.
respiratorv sinus arrhythmia; apnea, apneic bradycardia; activity; atropine treatment; marine mammals
Honolulu,
Hawaii
96822
mammals. The purpose of this communication is twofold: a) to study, in detail, the variations of heart rate in relatiwi to respiratory movements in the California sea lion; and b; to study the role of the vagus nerves in the control of heart rate during normal respiratory movements. METHODS
Three California sea lions were restrained in a special11 designed harness and pen (23). Respiratory movements WCR monitored with needle electrodes, attached subcutaneoush. at each side of the thoracic region, at the level of posteriw end of the foreflippers, via an impedance pneumograph (E & M, Houston). The output of the pneumograph \v~I; then recorded on a Beckman type R oscillographic recorder, Utilizing the same electrodes and a ground lead attached to the sacral region of the body, the ECG and instantaneoub heart rate were recorded via a ECG coupler and a cardiotachograph (Beckman Electronic Instrumentation, Calif. 1, respectively, and recorded on the above-mentioned rc’corder. Thus the respiratory movements, ECG, and heart rate could be displayed simultaneously. The respiratory fly\\ rate was also monitored via a face mask and a pneumotachograph (Statham, Calif.) to determine whether the impctiante record was an accurate representation of the respiriltory movements. The agreement was excellent (Fig. li# To assess the role of the vagus nerves in the regulation of’ the heart rate, 1.0 mg of atropine sulfate (Lilly, Indianapolis) was administered subcutaneously to each of two sea lioni;, weighing 40-50 kg. Their ECG and respiratory movements were recorded continuously for more than 1 hr. The effect of atropine on the heart rate was clear and lasted for more thau 1 hr in both cases. No ill effect attributable to the administration of atropine was observed during or after the expcriment.
vagus
ARE numerous reports on diving bradycardia in marine mammals (1,6, 22) ; increased vagal tone is the accepted mechanism of the bradycardia, although the sympathetic component has not been studied. On the other hand, spontaneous variations of heart rate, with respiration, in the resting animal have been mentioned only casually in a few species of seals and porpoises. In 1935, Irving et al. (13) reported that the respiratory variations in cardiac frequency and peripheral vascular tonic rhythmicity were more obvious in seals than in terrestrial mammals. They noted that cardiac slowing is associated with the respiratory pause. Bartholomew (3) observed in the adult northern elephant seal that the pulse rate during apnea was approximately 15 % lower than during eupnea. The arrhythmia was not obvious in the young pups. Similar results were obtained in the Weddell seal (18), while Z- to 4-year-old fur seals showed marked arrhythmia (10). The accelerated heart rate was associated with the period of rapid expiration and inspiration, which was completed in 1 or 2 sec. A similar respiratory-induced variation in the cardiac frequency had also been reported in the Pacific bottlenose dolphin (4, 11). Thus, it appears that a pronounced respiratory sinus arrhythmia is a wide-spread phenomenon among marine THERE
RESULTS
RelationshiP between respiratory cycle and heart rate. A and H in Fig. 1 signify the beginning and end of expiration, arld B and C the beginning and the end of inspiration. The rtx$piratory cycle of the California sea lion consists of a rapid expiration and inspiration, in succession, followed by a long postinspiratory apnea until the next expiration. The respiretory frequency is 4-5/min at normal body temperatuns. When the body temperature is elevated, the respiratory frequency may increase slightly but the sea lions do not par11 under hyperthermic conditions (23). The duration of the 260
RESPIRATORY
VARIATION
OF
HEART
261
RATE
2. Heart rate during various phases in California sea lion
of respiratory cycle
TABLE
Animal
N
12 9 28 10 24 17 15
Corky Corky 0 iZy 0 iZy Zal Zal Zal
1. Effect of respiration on heart rate of a California sea lion. from top, represent pneumotachogram, impedance pneumogram, 1-set time signal, ECG, and heart rate, respectively. A-B, and B-C are expiratory and inspiratory phases, respectively. FIG.
Traces,
1. Duration
MBLE
L
J
1
-’
4
84.8
63.6~t3.6 93.2h6.1 58.4rt2.1 76.Oh8.1 95.5zt4.8 74.oZt3.0 75.5Zt4.4
0.17&0.08 0.15~tO.06 0.39Ito.03 O.ZO=tO.O7 0.23&0.04 0.27&0.06 0.36kO.06
76.6
0.25
“\,
09
sea lion
J
78.5rt4.0 96.2&6.1 57.2&l .4 83.4~t8.5 103.2h4.5 82.3h3.2 93.Lt6.2
Heart rate = the Values are means =fi SE beats per minute. number of heart beats in each phase of the respiratory cycle was counted, then converted to minute rate. Onset of tachycardia = the starting point of tachycardia in relation to the beginning of inspiration.
of bhases of resbiratorv cycle J
m California
117.5&l .7 122.3~t3.7 94.4zt3.8 112.8&l .8 123.8~t2.4 112.8h6.1 115.7Zt3.0 114.2
Av
Onset of Tachycardia, set
Expiration
Inspiration
1
I
.4nimal Corky Corky Ody Ody %a1 %a1 %a1
N
12 9 28 10 24 17 15
Expiration
Inspiration
1.57~kO.23 1.05&O. 19 1.37&0.12 1.3O~tO.02 1 .Ol~O.ll 1.31rto.14 1.201tO.07
1.18ZtO.08 0.81~tO.13 0.96ztO.04 1.45rto.05 0.97zko.05 1.06&O. 10 1.08~tO.03
1.25
.\vg
Apnea
Total
13.02~t1.15 12.03&2.90 14.39M.29 8.64M.58 11.72&l .79 13.38&l .32 12.23h2.39
1.07
12.20
seconds.
N
15.77M.12 13.89h2.99 16.73M.27 11.39M.60 13.70&l .79 15.75&l .31 14.51~t2.41 14.53
$
06
!z
03
03
I-
02L
t LI~I~III~~~~~~II[~~I”I”‘J
0
Values studied.
are
means
&
SE
=
number
of cycles
entire period of respiratory gas movement is about 2-3 set, on the average (Table 1). The remaining time of a respiratory cycle is a period of apnea (Table 1). Thus respiration in the California sea lion is characterized by a periodic postinspiratory breath hold. The apnea accounts for 84 % of the respiratory cycle (Table 1). The inspiratory phase was shorter than the expiratory phase (Table 1). At the end of inspiration (C in Fig. l), the sea lion expired a very small arnount of air before holding its breath. The heart. rate accelerates almost immediately following the beginning of inspiration. The onset of cardioacceleration in relation to the beginning of inspiration was studied in 115 respiratory cycles, from three sea lions on seven separate occasions. The tachycardia started, on the average, 0.25 set after the onset of inspiration (Table 2). The onset of tachycardia occasionally appeared before or at the beginning of inspiration. The heart rate remained low during the expiratory phase (A-B in Fig. 1). The average heart rate during this period was lower than that of the apneic period (Table 2) Heart rate during apneic phase. The apneic phase of the respiratory cycle is defined as that from the end of inspiration to the beginning of the next expiration. The heart rate slows down to a low level following completion of inspiration, abruptly in the great majority of cases, occasionally gradually (Fig. 1). The changes in heart rate during the course l
I to
L’,+
I
2
4
6
6
IO
12
14
16
18
20
22
24
26
TIME AFTER APNEA (SECDNDS) FIG. 2. Cardiac interval during course of apneic phase of a normal respiratory cycle of a male California sea lion (Gorky). Inset is a schematic drawing of pneumotachogram of a respiratory cycle. E, expiration; I, inspiration; Apnea, from end of inspiration to beginning of next expiration. End of inspiration was taken as zero time. Different symbols represent different respiratory cycles.
of apnea are qualitatively similar among the sea lions when the successive R-R intervals are plotted against the time course of apnea, taking the end of inspiration as zero time, regardless of the duration of apnea. Figure 2 depicts four apneic cycles with two long apneic periods and two short periods. The similarity in cardiac response is striking. The R-R intervals started to lengthen immediately after the completion of inspiration, returned to end-expiratory levels 23 set later, then settle down to a low level of heart rate. During the course of apnea there are occasional bursts of two or three fast heart beats occurring either regularly (Fig. 2) or irregularly. The actual record of the occasional bursts ’ of heart rate can be seen in Fig. 3. Body temperature and heart rate during apneic phase. The longest R-R interval during the apneic phase tended to be less when the body temperature was elevated, by exposure to air at 35C for 3 hr, than during normothermic conditions (Fig. 4). In Fig. 4, the longest R-R interval during a given apnea is plotted as a function of the total duration of the apneic period. There is a clear trend for the longest R-R interval to be positively correlated with the duration of the apneic period.
262
LIN,
IMPEDANCE PNEUMOGRAPH
FOG. 3. Occasional of respiratory cycle. spiration.
bursts Arrows
of rapid heart on top trace
0
l
rate during apneic indicate beginning
phase of in-
0
l
0 l
TO 12 c 35C
Tr 3639 38-39
C C
Efect of atrojke on heart rate. The effect of atropine on the heart rate was tested in two sea lions. The results in these two cases are qualitatively similar except with regard to the time course. Approximately lo-15 min after the administration of atropine sulfate (1 mg/animal), the bradycardia during the apnea gradually disappeared. The maximal heart rate during the inspiratory phase remained unchanged. The maximal effect of atropine was observed 20 min in one animal, Oily (Fig. 5), and 40 min in the other animal, Zal, after the administration of atropine. At that time, the respiratory effect on the heart rate was negligible, only a very small variation of heart rate with respiratoion culd still be seen (Fig. 5). DISCUSSION
California sea lions exhibit a clear respiration-related variation in heart rate. The cardiac acceleration was
in
MATSUURA,
AND
WHITTOLY
phase with the inspiratory phase of a normal respirator) cycle. The time lag between the onset of inspiration and the cardioacceleration was less than one-half of the shortest cardiac interval. This suggests that the tachycardia in response to the inflation of the lungs was effected directly by the central nervous system, i. e., the inspiratory activity in the respiratory center inhibits the cardioinhibitory activity of the vagus nerves. The final common pathway is by way of vagus nerves. Alternatively, it is possible that without an) changes in the activity of the vagus nerves, the excitation of the inspiratory ten ter reactivates the cardiac accelerator nerves, assuming that the sympathetic activity to the heart was minimal during the apneic and expiratory phase of the cycle. Our results showed that after treatment with atropinc: the maximal heart rate during inspiration was not altered, and the variation in the heart rate with respiration diminished in spite of the fact that the inflation and deflation activities of the lung continued, suggesting that the activity of the cardiac sympathetic component remained constant in all phases of the respiratory cycle and that heart rate variations attributable to respiration reflect the marked periodic fluctuation of vagal activity. There was no phase shift with the respiratory frequencies observed (4-8/min). Whether the phase angle of the respiration-heart rate response in sea lions is respiratory frequency dependent, as in man (2, 15), should be investigated. A small residual respiratory effect on the heart rate can still be observed after atropine treatment (Fig. 5). It may be argued that this residual variation in heart rate may represent a respiratory fluctuation in syrnpathetic activity. However, the magnitude of this effect is small and it can play no significant role in the heart rate It may in fact have been due to the response to respiration. fact that the parasympathetic blockade by atropine, at the dosages used, was not complete. The California sea lion appears to be more sensitive than man and the dog to atropine sulfate (0.020-0.025 mg/kg, SC). In comparison, Jose and Collison (14) used 0.04 mg/kg to block the parasympathetic component of the heart in man and 0.2 mg/kg in the do? (15). It has been established in the harbor seal (20), porpoise (12), and the duck (2 1), either by vagotomy or by inthat the diving bradycardia is the result jection of atropine, of an increased vagal tone. It appears that the same mechanism is operating during the naturally occurring periodic apnea. The increased vagal tone continued through the e>;piratory phase of the cycle. On the other hand, it can be argued that the constant vagal tone is periodically suspended during the inspiratory phase. The maximal heart rate in the inspiratory phase of the respiratory cycle was relatively constant among animals (Table 2, Figs. 2 and 5). However, the heart rate is more labile during the apneic-expiratory period (Table 2, Figs, 2 and 3). There is a trend for the longest R-R interval to be positively correlated with the duration of apnea. This is to be expected since the cardiac slowing is a continuous process throughout the apneic-expiratory period, unless interrupted by an occasional burst of rapid heart rate. The physiological significance and mechanism of these occasional bursts of rapid heart rates have not been examined. It has been shown in man also that the heart rate oscillates occasionally during the course of a breath hold (9). The normal heart rate of the California sea lion consists of
RESPIRATORY
VARIATION
FIO. 5. Effect of atropine lion (Oily). Traces from ICG, and cardiotachogram,
OF HEART
RATE
on heart rate of a female California sea top represent impedance pneumogram, respectively. 15, 20, and 50 min indicate
n low level for 84 % of the time (Table 1) and for the remaining period it is at a high level, approximately twice that cluring the apneic and expiratory phasesof the respiratory cycle. It is interesting to note that during a voluntary dive the California sea lion and harbor seal (5, 7) achieved no greater bradycardia than that of the normal periodic apnea in air (Fig. 5). Thus it appears that the diving bradycardia in the California sealion involves only the elimination of the periodic tachycardia during a respiratory cycle. While it is undeniable that diving bradycardia exists and that it is an important adaptation to diving, the magnitude of the bradycardia may have been overestimated in the literature. It is concluded from these experiments that the naturally occurring bradycardia associatedwith the apnea and expiratory phasesof the respiratory cycle was achieved by elimination of periodic tachycardia which was associated with the inspiratory phaseof the respiratory cycle. Since the phaseshift of the respiratory-heart rate response was negligible, it is argued that a central, direct control was involved. The postinspiratory apnea is an added advantage to the
263
time after inspiration.
administration
of atropine.
Arrows
indicate
beginning
of
sealion. The study of Knelson et al. (17) indicated that introducing an end-inspiratory pause in the dog significantly increased the alveolar gas exchange, without increase in total ventilation. They observed a high correlation between length of end-inspiratory pause and fractional increase in calculated alveolar gas exchange. During the course of evolution the sealion seemsto have chosenprecisely this mechanism. The gradual return of thoracic impedance to the preexpiratory level (Fig. 1) may represent a gradual change in the thoracic configuration as a result of redistribution of air inside the lung. The redistribution of the gasinside the lung may allow the animal to take full advantage of the postinspiratory pause. It’s also possible that it resulted from a drastic reduction in the gas exchange ratio during apnea (8, 1%. This work was supported by a grant Science Foundation and by the Naval velopment Center, Hawaii. Received
for publication
24 September
(GB 8393) Undersea
from the National Research and De-
1971.
REFERENCES 1. ANDERSON, H. T. Physiological adaptations in diving vertebrates. Physiol. Rev. 46: 212-243, 1966. 2. ANOELONE, A., AND N. A. COULTER, JR. Respiratory sinus arrhythmia: a frequency dependent phenomenon. J. Appl. Physiol. 19: 479-482, 1964. 3. BARTHOLOMEW, G. A., JR. Body temperature and respiratory and heart rates in the northern elephant seal. J. Mammal. 35: 211-218, 1954. 4. ELSNER, R. W. Diving bradycardia in the trained dolphin. Nature 212: 407-408, 1966. 5. E~NER, R. W. Heart rate response in forced versus trained experimental dives in pinnipeds. Hvalradets Skrifer 48: 24-29, 1965. 6. ELSNER, R. W. Cardiovascular adjustments to diving. In: The edited by H. T. Anderson. New York: Biology of Marine Mammals, Academic, 1968, p. 117-145. 7. ELSNER, R. W., D. L. FRANKLIN, AND R. L. VAN CI-I~ERS. Cardiac output during diving in an unrestrained sea lion. Nature 202: 809-810, 1964. 8. HONG, S. K., Y. C. LIN, D. A. LALLY, B. J. B. YIM, N. KOMINAMI, P. W. HONG, AND T. 0. MOORE. Alveolar gas exchanges and
9.
10.
11.
12.
13.
14.
15.
cardiovascular functions during breath holding with air. J. J. Appl. Physiol. 30: 540-547, 1971. HONG. S. K.. T. 0. MOORE. G. SETO. H. K. PARK. W. R. HYATT. AND E. M. BERNAUER. Lung volumes and apneic bradycardia in divers. J. A#. Physiol. 29: 172-176, 1970. IRVING, L., L. J. PEYTON, C. H. BAHN, AND R. S. PETERSON. Action of the heart and breathing during the development of fur seals (Callorhinus ursinus). Physiol. Zool. 36: l-20, 1963. IRVING, L., P. F. SCHOLANDER, AND S. W. GRINNELL. Significance of the heart rate to the diving ability of seals. J. Cellular Comb. Physiol. 7: 283-297, 1935. IRVING, L., P. F. SCHOLANDER, AND S. W. GRINNELL. The respiration of the porpoise, Tursiops truncafus. J. CelIular Camp. Physiol. 17: 145-168, 1941. IRVING, L., 0. M. SOLANDT, D. Y. SOLANDT, AND K. C. FISHER. The respiratory metabolism of the seal and its adjustment to diving. J. Cellular Camp. Physiol. 7: 137-151, 1935. Josn,A. D., AND D. COUIS~N, The normal range and determinants of the intrinsic heart rate in man. Cardiovascular Res. 4: 160-167. 1970. JOSE, A. D., AND F. &ITT. Cardiac function after combined beta,
I
264 blockade. The relationship of adrenergic and cholinnergic intrinsic rate to contractile force of the heart in dogs. Circulation Res. 21, Suppl. 3: 231-242, 1967. 16. KELMAN, G. R., AND K. T. WANN. Studies on sinus arrhythmia. J. Physiol., London 2 11: 6 l-62, 1970. 17. KNELSON, J. H., W. F. HOWATT, AND G. R. DEMUTH. Effect of respiratory pattern on alveolar gas exchange. J. ApPl. Physiol. 29: 328-331, 1970. l-8. KOOYMAN, G. L. An analysis of some behavioral and physiological characteristics related to diving in the Weddell seal. Antarctic Res. Ser. 11: 227-261, 1968.
LIN,
MATSUURA,
AND
WHITTOW
19. LANPHIER, E. H., AND H. RAHN. Alveolar gas exchange during breath holding with air. J. ApPl. Physiol. 18 : 478-482, 1963. 20. MURDAUGH, H. V., JR., J. C. SEABURY, AND W. L. MITCHELL. Electrocardiogram of the diving seal. Circulation Res. 9 : 358-36 1, 1961. C. De la resistance des canards d l’asphyxie, J. Physiol. ‘lo RICHET, Pathol. Gen. 1: 64 l-650, 1899. 22 . SCHOLANDER, P. F. The master switch of life. Sci. Am. 209: 92-106, 1963. 23. WHITTOW, G. C., D. T. MATSUURA, AND Y. C. LIN. Temperature sea lion (Zalophus californianus). regulation in the California Physiol. 2001. In press.
