JOURNALOF

APPLIED

PHYSIOLOGY

Vol. 39, No. 5, November

1975.

Printed

in U.S.A.

Slow respiratory stimulant effect of h yperoxia in chemodenervated decerebrate

cats

R. ROSENSTEIN, L. E. MCCARTHY, AND H. L. BORISON I)epartment of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire and Veterans Administration Center, White River Junction, Vermont 0.5001

ROSENSTEIN, R., L. E. MCCARTHY, AND H. L. BORISON. Slow respiratory stimulant effect of hyperoxia in chemodenervated decerebrate cats. J. Appl. Physiol. 39(5): 767-772. 1975.-A direct stimulating action of oxygen on the CO:! respiratory control system was determined from steady-state and dynamic observations in unanesthetized decerebrate cats. In peripheral nerve-intact animals, inhalation of oxygen (1 atm) produced a small but significant shift to the left as well as a decrease in slope in the steady-state VT vs. log ~~~~~ relationship. Carotid sinus neurotomy more than doubled the shift, to the extent that the mean ~~~~~ apneic point was lowered by 6.5 mmHg. Neither vagotomy nor chronic ablation of the area postrema had any detectable influence on the stimulating effect of oxygen on CO2 responsiveness. The arterialalveolar Pcoz difference, prior to and following carotid chemodenervation, remained unchanged or was increased by a negligible amount during oxygen inhalation. The oxygen threshold for respiratory stimulation, obtained isocapnically, occurred between 115 and 200 mmHg; VT then increased exponentially tending to level off as PA o2 approached 1 atm. The dynamic response to sudden presentation of oxygen after carotid chemodenervation consisted of a monotonic rise in VT, starting after 20-30 s with a tip of about 75 s.

isocapnic steady-state respiratory sponse dynamics; area postrema

response ablation;

to oxygen; carotid

oxygen resinus nerve

section; vagus nerve section

IT HAS BEEN SHOWN in a number of mammalian species, including man, that sudden inhalation of oxygen results promptly in a depression of breathing often followed by stimulation (5, 8, 10, 17). The depressant effect is attributed to a reduction of peripheral chemoreflex drive. The mechanism of the subsequent stimulation is less certain but it is usually ascribed to an elevation of tissue PCO~in the central nervous system through the well-known Haldane effect of oxygen (8). The present study was undertaken to examine the respiratory stimulant action of oxygen given up to 100 % at 1 atm of pressure in unanesthetized decerebrate cats subjected to peripheral receptor denervations. We have chosen to use tidal volume (VT) as the respiratory response variable for two reasons. First, it has been demonstrated in this laboratory that VT is the direct measure of central CO2 responsiveness over the entire physiological range down to the apneic point (6, 15). Second, we have already reported that the vagally mediated interaction between respiratory frequency and VT is not affected by alterations in alveolar oxygen tension (13).

037.55;

Accordingly, steady-state respiratory effects of oxygen were quantified by shifts produced in the VT vs. log ~~~~~ regression line. Additionally, dynamic respiratory effects of step forcing with oxygen were characterized by the manner of development of the VT responses occurring at fixed PA co2 levels. METHODS

Experiments were performed in 33 cats. The animals were decerebrated under halothane anesthesia. The decerebration procedure consisted in ligating the common carotid arteries and transecting the brain stem at the midcollicular level followed by suction removal of about 0.5 cm of the brain rostra1 to the transection. The acute experiment was usually begun 18 h after the termination of anesthesia. Carotid receptor denervation consisted in cutting Hering’s nerve between mass ligatures that included the medial branches (occipital, ascending pharyngeal, and internal carotid arteries) of the carotid arterial bifurcation. The vagus and accompanying sympathetic nerves were sectioned at the midcervical level. The aortic depressor nerve was identified and sectioned at its junction with the root of the superior laryngeal nerve. Chronic lesions of the area postrema in the medulla oblongata were made by thermal cauterization under direct visualization. Functional effectiveness of the lesions was ascertained in advance of the acute experiment by emetic refractoriness to apomorphine injected into the cerebral ventricles. Lesion placement was also confirmed histologically. Respiration was recorded by means of a whole body constant-volume plethysmograph provided with pass-through connections for tracheal and arterial intubations and for a rectal thermistor probe. Pressure change was recorded with a sensitive transducer as the measure of VT. The plethysmograph was calibrated at the end of each experiment by injecting a known volume of air into the chamber while the cat’s tracheal tube was occluded. Body temperature was monitored with a telethermometer and maintained between 37 and 38°C by use of a water-circulated metal heat exchanger under the cat in the plethysmograph. A Beckman CO2 analyzer placed in series with a Westinghouse O:! analyzer served to measure continuously the airway CO2 and Oa concentrations through a sampling catheter in the tracheal cannula. Gas concentrations, respiratory excursions, and blood pressure were recorded on a Brush rectilinear

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (129.186.138.035) on January 16, 2019.

768

ROSENSTEIN,

polygraph. In the measu rement of PA coZ a correction was shift resul ting from the increased made for the calibration concentration of oxygen. Pace, and pHa d eterminations were made wi .th a Radiometer CO2 el .ectrode and capillary blood electrode on samples obtained anaerobically from a carotid artery. Cog, 02, Nz, and air were delivered through independently valved flowmeters into a mixing manifold. The gas mixtures were administered by excess flow over the external port of the tracheal cannula. End-expiratory CO2 and O2 tensions were controlled manually by fine adjustment of gas flow rates. These gas inhalations were maintained for a minimum of 4 min for CO2 and for 5-30 min for 02. The apneic point was determined as the extrapolated CO2 intercept of the fitted straight-line VT-log ~~~~~ relationship. Hypocapnic points between the resting point and apneic point were obtained by hyperventilating to a steadyic positivestate end-tidal ~~~~~ by either intrapulmon negative-pressure ventilation. pressure or extracorporeal Abrupt cessation of the respiratory pump immediately unmasked ongoing breath .ing of diminished amplitude. The first spontaneous breath was referred to the immediately preceding steady-state level of COZ. A delay in this first breath indicated that the ~~~~~ was below the apneic threshold due to excessive hyperventilation. Such effects were not used for generating the VT-log ~~~~~ response line. For statistical analysis, VT vs. ~~~~~ plots of the data from individual experiments under different conditions were reduced to separate group mean linear regression lines by the method of least squares. Significance of differences between slopes and intercepts were determined by use of the Student two-tailed t-test. RESULTS

Effect of carotid sinus neurotomy on the steady-state response to 100% oxygen. Figure 1 shows the influence of oxygen inhalation on the VT vs. log ~~~~~ relationship before and after CONTROL 120-

pno* (mmHg) ca.1 >650

100

“T

I0

0 0

-

80-

(ml)

pA

co2

1. Influence of oxygen on the VT-log PACO~ relationship prior to (Control) and following carotid sinus neurotomy (CSNX). Encircled symbols represent resting ventilation values; CO2 was administered to achieve higher values and hyperventilation was employed for the lower values (see METHODS). Note that the CO2 intercepts at zero VT for this animal fit in at the low end of the population range given in Table 1. FIG.

MCCARTHY,

AND

BORISON

1. Effect of administration of 100 5% 02 at I atm on slopes and intercepts of VT-kg PA c 0 2 relationship in cats before denervation (intact), after carotid sinus neurotomy (CSNX), and after carotid sinus neurotomy plus bilateral vagotomy (CSNX + VAGX) TABLE

Slope [AVT/AlogPAco2]

Intercept,

mmHg

[PACO~ at zero VT]

A Intercept, -Hg bC02

at

zero AIR

02

AIR

02

VT(k)PACo2

at

zero VT(&)]

Intact W = 12) CSNX (N = 8) CSNX + VAGX W = 7)

588 zt52 523 xk52 932 *173

467 zt55” 420 ~t63~ 750 zt188”

24.1 ltzl.3 29.5 xk2.2 27.2 zt2.0

21.5 ztl.4 23.0 zt2.3 21.4 zt2.6

2.6 1t0.6~ 6.5 zkl.2” 5.8 zkl .2f

N= no. of cats; values are means + SE. a P < 0.008 for difference from slope in air. b 0.09 < P < 0.1 for difference from slope in air. c 0.05 < P < 0.06 for difference from slope in air. d P < 0.001 for difference in intercept between 02 and air. “PC 0.004 for difference from A Intercept in Intact cats. f P 5 0.02 for difference from A Intercept in Intact cats.

carotid sinus neurotomy in one cat. Characteristically, the nerve section itself results in a shift to the right in the VTCO2 response line (6) and in a loss of reactivity to oxygen lack (15). However, as can be seen in Fig. 1, the influence of oxygen excess not only persisted but was magnified following the denervation. It is noteworthy that the steady-state effect of hyperoxia on CO2 responsiveness after carotid sinus nerve section occurs in the same direction as the effect of hypoxia when the carotid sinus nerve is intact. Results obtained in 8 cats subjected to carotid sinus neurotomy (CSNX) are compared in Table 1 with data from 12 nondenervated cats. The acid-base status of these preparations is consonant with that observed by Herbert and Mitchell (7) in unanesthetized brain-intact cats. It is evident that the inhalation of oxygen in our peripheral nerve-intact cats resulted in a small but significant reduction in the slope as well as in the zero intercept (apneic point) of the VT-CO2 response line; a decrease in the CO2 intercept occurred in 10 of the 12 cats. By contrast, the mean shift in the intercept due to oxygen was more than doubled following carotid receptor denervation (6.5 mmHg shift in CSNX cats as against 2.6 mmHg shift in Intact cats), but the difference in slope resulting from oxygen intake was no longer significant after the denervation. Thus, an influence of oxygen to reduce the set point (apneic threshold) of CO2 responsiveness was unmasked by interruption of the carotid sinus nerve. Similar results were obtained in two animals that had not been decerebrated but were studied promptly after they had been anesthetized with pentobarbital. E$ect of vagotomy. Unlike carotid receptor denervation, midcervical vagotomy produced no consistent effect on the ventilatory response to oxygen. Indeed, combined denervation, i.e., carotid sinus neurotomy plus vagotomy, performed in seven cats, yielded no greater effectiveness in the CO2 set-point shifting action of oxygen than did carotid denervation alone (see Table 1). The characteristic effect of vagotomy on the VT-CO2 relationship in air is an increase

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (129.186.138.035) on January 16, 2019.

RESPIRATORY

STIMULANT

EFFECT

OF

HYPEROXIA

in slope of the regression line (6). Nevertheless, the presence of excess oxygen did not significantly affect the slope of the VT-CO2 response line after vagotomy plus carotid sinus neurotomy. Efect of area postrema ablation. It was claimed but then disproved that the area postrema acts as the central chemosensitive site for CO2 (6, 11). This notwithstanding, a physiological role for the area postrema, aside from its known chemoreceptor function in vomiting, remains an attractive possibility owing to its strategic location in relation to the cerebrospinal fluid and to the cranial nerve nuclei of the medulla oblongata (2). We therefore tested the effect of oxygen on the VT-CO2 response line in three cats which had chronic lesions made in the area postrema and were subjected acutely to carotid sinus neurotomy and/or vagotomy after decerebration. Typical results are shown in Fig. 2. Two conclusions follow from these experiments. First, it was confirmed that central CO:! responsiveness is retained after peripheral chemodenervation plus ablation of the area postrema in decerebrate cats. Second, the area postrema plays no essential role in the stimulant effect of oxygen on the ventilation. Graded steady-state effect of oxygen on VT at constant pAcoz. Eight experiments were performed in which ~~~~~ was manually controlled at a fixed level while PACT was varied intermittently between ca. 115 and 700 mmHg. The carotid chemoreceptors were denervated in all cases. Results obtained in a single animal under isocapnic conditions (PA~OP - 35 mmHg) are shown in Fig. 3A. The main facts that emerge from this experiment are : a) the PACT stimulation threshold was approximately 150 mmHg ; b) VT was almost doubled at the PACT of 660 mmHg where the effect of oxygen tended to level off. Normalized data for the entire series of experiments are shown in Fig. 3B. Isocapnic PA~O~ levels for the group of animals varied from ca. 32 to 44 mmHg. It can be seen that the steepest rise in the VT response to oxygen occurred between 200 and 300 mmHg. 140

IOO-

", (ml)

r

A

“T

(ml)

60 t

/

25

I

1

1

1

200

100

300 pA

0,

1

400

I

1

1

500

600

700

hmHg)

FIG. 3. Steady-state relationship of VT vs. PACT at constant PACO~ after carotid sinus neurotomy. A: in a single animal; B: normalized data from 8 animals based on percent of maximum VT response.

(IN

AIR-1 ( IN 02---I 0

L

INSPf

50ml I

200

I’ P I

4

n

L

I

‘3Osec

I ’

3min

3min

4. Polygraph recording of the ventilatory response to oxygen under isocapnic conditions following carotid sinus neurotomy. Note the correction made in the CO2 recording for the calibration shift resulting from analyzing COs in oxygen as against CO2 in air. The peaks of the CO2 excursions represent PACO% . The nadir of the 02 excursions represent PAoz . FIG.

#i

80-

>

PA CO, 2. ing carotid animal in olated zero tion range

80

B.F? m m 100 Lr

i

FIG.

769

650

-A--

h-dig)

Influence of oxygen on the VT-log PACO~ relationship followsinus neurotomy plus vagotomy (CSNX + VAGX) in an which area postrema was ablated. In this case, the extrapVT intercept of CO2 falls at the upper end of the populagiven in Table 1.

Dynamic efect of 100% oxygen on VT at constant PA co2. Figure 4 illustrates the manner in which PA~O~ was externally controlled at a constant level during the course of the ventilatory response to a quasi-step change in PACT. It is seen in the polygraph tracing that the latency of VT response onset was somewhat less than 30 s, and that a steady state was achieved within 4 min after the presentation of oxygen in a carotid chemodenervated cat. The accompanying change in respiratory frequency (3-4 breaths/min) coincides with that previously reported for an equivalent change in VT (13). A comparison is made in Fig. 5 of the time courses of the VT response to sudden inhalation of 100 % oxygen at con-

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (129.186.138.035) on January 16, 2019.

770

ROSENSTEIN,

trolled carbon dioxide levels before and after certain peripheral denervations. In this case, the denervations included carotid sinus neurotomy, aortic depressor nerve section, and cervical sympathectomy, with the main trunk of the vagus nerve remaining intact. It should be pointed out that carotid chemodenervation alone suffices to abolish the VT stimulation response to oxygen lack (15) and it also suffices to abolish the dynamic depressant effect of oxygen excess. Nevertheless, the additional nerve sections in the present experiment were made to ensure the elimination of other potential feedback sources in blood gas regulation. In the peripheral nerve-intact preparation (control), oxygen administration produced the expected immediate decrease in VT which reached its nadir in about 30 s and its point of reversal in 2 min. By contrast, following the peripheral denervations, the dynamic response to oxygen inhalation consisted only of ventilatory stimulation starting after about 0.5 min with a response half-time of 75 s. Effect of oxygen on the alveolar estimation of arterial Pco~. If the inhalation of oxygen were to alter systematically the transfer of carbon dioxide between the arterial blood and the alveolar gas, this would result in a spurious shift in the VT-CO~ response line and thereby suggest falsely a change in CO:! responsiveness. Accordingly, three types of experiments were performed in order to compare the status of arterial blood CO2 tension alongside the alveolar measurement of PCO~ before and during the administration of oxygen. These comprise I) the corresponding arterial blood pH measurement, 2) the indirect arterial blood Pcoz measurement by the Astrup method, and 3) the direct measurement of arterial CO:! tension with a Pcoz electrode. The results of one experiment comparing pH, with PACES under four experimental conditions, namely, air and oxygen inhalation before and after carotid chemodenervation, are shown in Fig. 6. Steady-state measurements were obtained over a pH, range of 0.16 unit and corresponding ~~~~~ range of 15 mmHg. Remarkably, all the points fall on 30!-

0 - CONTROL 0 - AFTER

CSNX,

AORTIC

20AVT (ml)

CERV.

I- 0.

l

a

0

o 0

SYMPX.

0

0

lo-

0

NX,

0

0 O

0

0

0

0

0 0

I”

0

1

I

1

50

100

150

0, ON

1

200 TIME

1

250

1

300

1

350

1

400

I

450

(set)

of tidal volume response to oxygen under isocapnic conditions at P~co~ = 32.5 mmHg prior to (Control) and at PAcoz = 35 mmHg following carotid sinus neurotomy (CSNX), aortic nerve section (Aortic NX), and cervical sympathectomy (SYMPX). Zero level represents the mean VT observed for the 5-min period preceding 02 administration. Actual VT values & SD were o 55.9 zt 1.65; 0 68.3 It 0.85. Note that following the nerve sections oxygen elicited only an increase in VT after a latency of approximately 30 s. Different isocapnic levels were selected before and after denervations because of the shift in the VT-CO2 response line and the desirability of maintaining tidal volumes approximatelv eaual.

A 00

\

7.4(

MCCARTHY,

0

PA 02

AND

CONTROL

CSNX

BORISON

(mmlig) 0 A aA

ccl.

110

0

A

A*

>

650

0

A

7.3l

pHII 7.3;

7.2t

7.2(

+ t

L

1

20 pA

co2

25 ImmHg)

1

30

J

35

FIG. 6. Graphic relationship between PACO~ and pH, under normoxie and hyperoxic conditions in a cat prior to (Control) and following carotid sinus neurotomy (CSNX). VT-log PACO~ data for this animal are shown in Fig. 1. Dashed line represents the PH,-PAco~ relationship that would have been observed in the presence of 02 following response line been due entirely to CSNX had the shift in the VT-PAC~~ an increase in the Paco2-PAco2 gradient. Position of this hypothetical ine was established by taking corresponding PACO~ values at iso-VT levels shown in Fig. 1 which determine the displacement of the line as indicated by the arrows.

one line and so indicate that a constant CO2 blood-alveolar transfer state prevailed under all testing conditions. Indeed, the graph data points for oxygen inhalation after carotid chemodenervation should have fallen on the displaced pH&‘~co, line drawn in Fig. 6 if, in fact, the observed shift in CO2 responsiveness (see same experiment in Fig. 1) had resulted spuriously from CO2 retention in the pulmonary capillary blood. Similar results were obtained in a second experiment with pH, measurement. Two additional experiments were performed in which arterial blood Pco2 determinations were made by Astrup and CO2 electrode methods, respectively, in cats with carotid sinus nerves cut. In both experiments, the arterialalveolar Pcoz difference was increased by no more than 1.7 mmHg during the inhalation of oxygen; yet the apneic point of CO2 responsiveness was shifted 7.6 mmHg in one experiment and 5.1 mmHg in the other. Furthermore, the arterial-alveolar Pco2 difference during air breathing was essentially zero when measured with the CO2 electrode. Thus, we could obtain no evidence for an influence of oxygen on the arterial-alveolar Pcoz difference of sufficient magnitude to account for the shift produced in the VTCO2 response line following carotid chemodenervation.

FIG. 5. Development

DISCUSSION

Characteristics of oxygen response. The prominent features of the respiratory stimulant response to oxygen in the decerebrate cat are as follows: 1) It is best expressed after peripheral chemodenervation. 2) Under steady-state conditions, it consists essentially of a parallel shift to the left in the VT-log ~~~~~ relationship. 3) The graded steady-state

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (129.186.138.035) on January 16, 2019.

RESPIRATORY

STIMULANT

EFFECT

OF HYPEROXIA

771

effect of oxygen on tidal volume, determined isocapnically, presents a nonlinear course starting at a threshold value of between 115 and 200 mmHg and rising most steeply below with step 300 mmHg PACT. 4) Its transient form, obtained forcing effected isocapnically, follows a long latency of onset (up to 30 s) and manifests a long response half time (about 75 s). 5) It is not affected by interruption of the vagal pulmonary inflation reflex with the consequent loss of respiratory frequency control. A probable central site of action. When the arterial chemoreceptor innervation is intact, the administration of oxygen silences the centripetal discharges which normally facilitate central CO2 responsiveness (15, 17). Elimination of this disfacilitatory action by means of peripheral chemodenervation leaves the stimulant effect of oxygen unopposed. Inasmuch as the known remaining chemoreceptive input to the respiratory controller resides in the brain stem, it follows that oxygen acts through a central locus to stimulate the respiration. It is safe, however, to exclude the area postrema as a possible site of action. Mechanism of action. In control-systems terms, the effect of oxygen on blood CO2 regulation can be characterized as a decrease in regulating set point with little or no change in controller gain. From the dynamic point of view, shifts in ventilation resulting from changes in peripheral chemoreceptor activity caused by oxygen deprivation occurs with minimal delay (5). P rompt shifts in COa set point also apparently result by way of a central process in transitions between sleep and arousal Hence, the long delay and long response time for the stimulant effect of oxygen point to the intervention of a physical or chemical rate-limiting step in the mode of action. The Haldane effect of oxygen is the first to suggest itself as a suitable explanation, namely that of an increase in the PCO~ difference due to a reduction in CO2 arteriovenous carrying capacity of the blood (8). However, a number of considerations militate against this explanation. 1) If the proposition is correct that central COB receptors lie on the arterial side of the brain capillaries, then those receptors should be relatively unresponsive to venous PCO~ (3). 2) The response onset to step forcing with oxygen would not be delayed beyond the time required for the oxygenation of hemoglobin which occurs within the transit time from lung to brain, amounting to approximately 5 s (see Daubenspeck (4)). 3) The better part of the stimulant effect of oxygen is completed well below 1 atm where the Haldane effect is just starting to manifest itself (8). Indeed, the presently observed effect of 02 at 1 atm amounted to a shift in ~~~~~ of 6.5 mmHg, whereas the change in Pvcoz predicted from the Haldane effect amounts to 2.4 mmHg at 1 atm Oz (16) and only 5.0 mmHg at 3.5 atm Oz (8). A plausible alternative to the Haldane effect is the contention of Lenfant (9) that oxygen increases the mean

(1,w

arterial-alveolar difference in PCO~ by altering the ventilation-to-perfusion ratios distribution. The measuremen t of alveolar CO2 ten .sion would then give an erroneously low value for arterial blood CO2 tension during the inhalation of oxygen, thereby yielding a spurious shift to the left in the VT-CO2 response line. However, in the present experiments we did not find an influence of oxygen on the arterialalveolar Pcoz difference of sufficient magnitude to account for the shift. Indeed, the results from direct and indirect determinations of the arterial-alveolar CO2 gradient indicate an influence of 02 much smaller than that observed by Lenfant. Thus Lenfant’s finding may be related to conditions that apply in a particular way to the human subject. Another possible explanation for the stimulant effect of oxygen is that it relieves a relative brain hypoxia. This is unlikely because the effect of hypoxia under the same experimental conditions is not evident until PACT falls below 80 mmHg (15). Moreover, in the peripheral nerveintact animal, hyperoxia causes a shift of CO2 responsiveness in the same direction as hypoxia which would hardly be consistent with the relief of ongoing deprivation of oxygen. The fact that the VT-log Proof regression line in the presence of oxygen remains linear and lies almost parallel to the regression line in air after peripheral chemodenervation indicates that the respiratory effect of oxygen is unrelated to associated changes induced in brain blood flow which further minimizes the influence of change in Pv coz. The stimulant effect of oxygen cannot be associated with the decerebration procedure since the same type of response was obtained in anesthetized cats that were not subjected to decerebration. A major possibility that remains is that oxygen acts on the central CO2 detector in one or both of two ways, namely, to reduce the reference level and/ or to increase chemoreceptor excitability, either of which would enlarge the error signal to yield an apparent downward shift in set point. No discrete mechanism presents itself by which the necessary changes in CO2 detection might be brought about through an action of oxygen. Nevertheless, the response delay suggests that a metabolic factor participates in the action. In conclusion, a stimulant action of oxygen that resides outside of the peripheral arterial chemoreceptors accounts largely, if not completely, for the respiratory adaptation that follows the initial depression of breathing observed in response to the continued inhalation of oxygen. This investigation was supported in part by Public Health Service Research Grant NS-04456 from the National Institute of Neurological Diseases and Stroke and Veterans Administration MRIS 99-03. A-preliminary report was presented at the 1974 meeting of the Federation of American Societies for Experimental Biology (Rosenstein et al., 1974 (14)). Received

for publication

20 January

1975.

REFERENCES 1. BELLVILLE, J. W., W. S. HOWLAND, J. C. SEED, AND R. W. The effect of sleep on the respiratory response to carbon Anesthesiology 20 : 628-634, 1959. 2. BORISON, H. L. Area postrema: chemoreceptor trigger vomiting-is that all? Life Sci. 14: 1807-1817, 1974. 3. BORJSON, H. L., AND L. E. MCCARTHY. CO2 ventilatory time obtained by inhalation step forcing in decerebrate AppZ. Physiol. 34 : 1-7, 1973.

HOUDE.

dioxide. zone

for

response cats. J.

4. DAUBENSPECK, J. A. Frequency analysis of CO2 regulation: afferent influences on tidal volume control. J. APPZ. Physiol. 35: 662-672, 1973. 5. DEJOURS, P. Control of respiration by arterial chemoreceptors. Ann. N. Y. Acad. Sci. 109 : 682-695, 1963. 6. FLOREZ, J., AND H. L. BORISON. Tidal volume in CO2 regulation: peripheral d enervations and ablation of area postrema. Am. J. Physiol. 212: 985-991, 1967.

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (129.186.138.035) on January 16, 2019.

772 7. HERBERT,

acid-base 1971.

ROSENSTEIN, D. A., balance

AND

in

R. A. MITCHELL. Blood gas tensions and awake cats. J. Appl. Physiol. 30: 434-436,

8. LAMBERTSEN, C. J. Effects of oxygen at high partial pressure. In: Handbook of Physiology. Respiration. Washington, D.C. : Am. Physiol. Sot., 1965, sect. 3, vol. II, chapt. 39, p. 1027-1046. C. Arterial-alveolar difference in PCO~ during air and 9. LENFANT,

oxygen breathing. J. A#. Physiol. 2 1: 1356-l 362, 1966. 10. MARSHALL, E. K., JR., AND M. ROSENFELD. Depression tion by oxygen. J. Pharmacol. Exptl. Therap. 57 : 437-457, 11. MASLAND, W. S., AND W. S. YAMAMOTO. Abolition of response to inhaled CO% by neurological lesions. Am. 203 : 789-795, 1962. 12. REED, D. J., AND R. H. KELLOGG. Changes in respiratory to CO2 during natural sleep at sea level and at altitude. Physiol. 13 : 325-330, 1958.

of respira1936.

ventilatory J.

Physiol.

response J. Apfll.

MCCARTHY,

AND

BORISON

13. ROSENSTEIN, R., L. E. MCCARTHY, AND H. L. BORISON. Rate versus depth of breathing independent of alveolar oxygen in decerebrate cats. Respiration Physiol. 19 : 80-87, 1973. 14. ROSENSTEIN, R., L. E. MCCARTHY, AND H. L. BORISON. Tidal volume response to hyperoxia in P&02-controlled chemodenervated unanesthetized decerebrate cats. Federation Proc. 33 : 456, 1974. 15. ROSENSTEIN, R., L. E. MCCARTHY, AND H. L. BORISON. Influence of hypoxia on tidal volume response to CO2 in decerebrate cats. Respiration Ph.ysiol. 20 : 239-250, 1974. 16. SAUNDERS, K. B., D. M. BAND, P. EBDEN, J. P. VAN DER HOFF, D. J. MABERLEY, AND S. J. G. SEMPLE. Acid-base status and gas exchange in the anaesthetized dog breathing pure oxygen. Respiration 29 : 305-316, 1972. 17. WATT, J. G., P. R. DUMKE, AND J. H. COMROE, JR. Effects of inhalation of 100 per cent and 14 per cent oxygen upon respiration of unanesthetized dogs before and after chemoreceptor denervation. Am. J. Physiol. 138: 610-617, 1943.

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (129.186.138.035) on January 16, 2019.

Slow respiratory stimulant effect of hyperoxia in chemodenervated decerebrate cats.

A direct stimulating action of oxygen on the CO2 respiratory control system was determined from steady-state and dynamic observations in unanesthetize...
1MB Sizes 0 Downloads 0 Views