Abstract
1. Ventilation (˙VE), tidal volume (VT), respiratory frequency (f) and arterial and end-tidal gas tensions were measured in seventy-one tracheostomized New Zealand white rats (∼ 405 g) anaesthetized with an initial dose of pentobarbitone followed by repeated small doses to ensure that a weak limb-withdrawal reflex remained.
2. O2 consumption (1.2 ml (s.t.p.d.) min-1 100 g-1), CO2 production (1.0 ml (s.t.p.d.) min-1 100 g-1), heart rate (357 min-1), ˙VE (43 ml min-1 100 g-1), Pa,CO2 (34 mmHg) and Pa,O2 (84 mmHg) in the control periods did not change significantly during the course of the experiment.
3. Inspirates of 21% O2 with 2-10% CO2, 15, 10 or 7.5% O2 with either no or sufficient CO2 to maintain normocapnia and 15 or 10% O2 with 4, 6 or 8% CO2 were tested. Steady-state responses were measured after 2 min of exposure.
4. Hypoxic—hypercapnic interaction on ˙VE, VT and f determined by a three-inspirate test ((i) hypoxia alone, (ii) hypercapnia and (iii) these hypoxic and hypercapnic levels combined) yielded various conclusions depending on the level of asphyxia examined. Essentially, the milder the asphyxia the more the interaction appeared additive or even multiplicative and the stronger the asphyxia the more the interaction appeared occlusive. However, this test is unsuitable for accurately showing interactions because the Pa,O2 achieved in asphyxia was higher than in hypoxia and the asphyxial Pa,CO2 was lower than in hypercapnia.
5. For isoxic conditions (Pa,O2 = 97, 77 and 51 mmHg), ˙VE and VT were related linearly to Pa,CO2 whilst f was related hyperbolically with convexity upwards (Pa,O2 97 mmHg) or downwards (Pa,O2 77 and 51 mmHg).
6. For isocapnic conditions (Pa,CO2 = 33, 40 and 48 mmHg), ˙VE and VT were inversely related to Pa,O2 with a hyperbolic curve (convexity downwards) whilst f was inversely and linearly related (Pa,CO2 33 mmHg) or constant (Pa,CO2 40 and 48 mmHg).
7. Multivariate analyses showed that the hypoxic—hypercapnic interaction was additive for VT but occlusive for ˙VE and f and the occlusion was more severe in the latter. This was illustrated graphically for the variable plotted against Pa,CO2 or Pa,O2 as parallel shifts in regression lines for VT, flatter regression lines for ˙VE during asphyxia and a virtually constant f during asphyxia.
8. ˙VE responses and sensitivities to hypoxia and hypercapnia, the shape of ˙VE, VT and f regression lines against Pa,O2 and Pa,CO2 and the type of hypoxic—hypercapnic interaction on each variable in the rat were compared with other species.
9. Possible causes of the occlusive hypoxic—hypercapnic interaction in the rat were considered.
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Selected References
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- Adams J. M., Attinger F. M., Attinger E. O. Medullary and carotid chemoreceptor interaction for mild stimuli. Pflugers Arch. 1978 Apr 25;374(1):39–45. doi: 10.1007/BF00585695. [DOI] [PubMed] [Google Scholar]
- Adams J. M., Severns M. L. Interaction of chemoreceptor effects and its dependence on the intensity of stimuli. J Appl Physiol Respir Environ Exerc Physiol. 1982 Mar;52(3):602–606. doi: 10.1152/jappl.1982.52.3.602. [DOI] [PubMed] [Google Scholar]
- Arieli R., Ar A. Ventilation of a fossorial mammal (Spalax ehrenbergi) in hypoxic and hypercapnic conditions. J Appl Physiol Respir Environ Exerc Physiol. 1979 Nov;47(5):1011–1017. doi: 10.1152/jappl.1979.47.5.1011. [DOI] [PubMed] [Google Scholar]
- Bartlett D., Jr, Tenney S. M. Control of breathing in experimental anemia. Respir Physiol. 1970 Oct;10(3):384–395. doi: 10.1016/0034-5687(70)90056-3. [DOI] [PubMed] [Google Scholar]
- CHAPIN J. L. Ventilatory response of the unrestrained and unanesthetized hamster to CO2. Am J Physiol. 1954 Oct;179(1):146–148. doi: 10.1152/ajplegacy.1954.179.1.146. [DOI] [PubMed] [Google Scholar]
- Cherniack N. S., Edelman N. H., Lahiri S. Hypoxia and hypercapnia as respiratory stimulants and depressants. Respir Physiol. 1970;11(1):113–126. doi: 10.1016/0034-5687(70)90107-6. [DOI] [PubMed] [Google Scholar]
- Cunningham D. J., Gardner W. N. A quantitative description of the pattern of breathing during steady-state CO2 inhalation in man, with special emphasis on expiration. J Physiol. 1977 Nov;272(3):613–632. doi: 10.1113/jphysiol.1977.sp012063. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Daubenspeck J. A., Ogden R. D. Estimation of response slopes in respiratory control using directional statistics. J Appl Physiol Respir Environ Exerc Physiol. 1978 Nov;45(5):823–829. doi: 10.1152/jappl.1978.45.5.823. [DOI] [PubMed] [Google Scholar]
- Drysdale D. B., Jensen J. I., Cunningham D. J. The short-latency respiratory response to sudden withdrawal of hypercapnia and hypoxia in man. Q J Exp Physiol. 1981 Jul;66(3):203–210. doi: 10.1113/expphysiol.1981.sp002550. [DOI] [PubMed] [Google Scholar]
- Falchuk K. H., Lamb T. W., Tenney S. M. Ventilatory response to hypoxia and CO2 following CO2 exposure and NaHCO3 ingestion. J Appl Physiol. 1966 Mar;21(2):393–398. doi: 10.1152/jappl.1966.21.2.393. [DOI] [PubMed] [Google Scholar]
- Favier R., Lacaisse A. Stimulus oxygène de la ventilation chez le rat éveillé. J Physiol (Paris) 1978;74(4):411–417. [PubMed] [Google Scholar]
- Flenley D. C. Methods and results of assessing the hypoxic ventilatory drive in patients and normal subjects. Bull Eur Physiopathol Respir. 1979;15 (Suppl):223–231. [PubMed] [Google Scholar]
- Fukuda Y., See W. R., Honda Y. Effect of halothane anesthesia on end-tidal PCO and pattern of respiration in the rat. Pflugers Arch. 1982 Jan;392(3):244–250. doi: 10.1007/BF00584304. [DOI] [PubMed] [Google Scholar]
- Gabel R. A., Kronenberg R. S., Severinghaus J. W. Vital capacity breaths of 5 percent or 15 percent CO 2 in N 2 or O 2 to test carotid chemosensitivity. Respir Physiol. 1973 Mar;17(2):195–208. doi: 10.1016/0034-5687(73)90061-3. [DOI] [PubMed] [Google Scholar]
- Gautier H., Bonora M. Effects of carotid body denervation on respiratory pattern of awake cats. J Appl Physiol Respir Environ Exerc Physiol. 1979 Jun;46(6):1127–1131. doi: 10.1152/jappl.1979.46.6.1127. [DOI] [PubMed] [Google Scholar]
- Gautier H. Pattern of breathing during hypoxia or hypercapnia of the awake or anesthetized cat. Respir Physiol. 1976 Aug;27(2):193–206. doi: 10.1016/0034-5687(76)90074-8. [DOI] [PubMed] [Google Scholar]
- Giese K., Berndt J., Berger W. Interaction of central and peripheral respiratory drives in cats. II. Peripheral and central interaction of hypoxia and hypercapnia. Pflugers Arch. 1978 May 31;374(3):211–217. doi: 10.1007/BF00585597. [DOI] [PubMed] [Google Scholar]
- HEMINGWAY A., NAHAS G. G. Effect of varying degrees of hypoxia on temperature regulation. Am J Physiol. 1952 Aug;170(2):426–433. doi: 10.1152/ajplegacy.1952.170.2.426. [DOI] [PubMed] [Google Scholar]
- HILL J. R. The oxygen consumption of new-born and adult mammals. Its dependence on the oxygen tension in the inspired air and on the environmental temperature. J Physiol. 1959 Dec;149:346–373. doi: 10.1113/jphysiol.1959.sp006344. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heeringa J., Berkenbosch A., de Goede J., Olievier C. N. Relative contribution of central and peripheral chemoreceptors to the ventilatory response to CO2 during hyperoxia. Respir Physiol. 1979 Aug;37(3):365–379. doi: 10.1016/0034-5687(79)90082-3. [DOI] [PubMed] [Google Scholar]
- Hey E. N., Lloyd B. B., Cunningham D. J., Jukes M. G., Bolton D. P. Effects of various respiratory stimuli on the depth and frequency of breathing in man. Respir Physiol. 1966;1(2):193–205. doi: 10.1016/0034-5687(66)90016-8. [DOI] [PubMed] [Google Scholar]
- Honda Y., Kreuzer F. PO2-ventilation response curve with normal pH and PCO2 in the dog. J Appl Physiol. 1966 Mar;21(2):423–433. doi: 10.1152/jappl.1966.21.2.423. [DOI] [PubMed] [Google Scholar]
- LLOYD B. B., JUKES M. G., CUNNINGHAM D. J. The relation between alveolar oxygen pressure and the respiratory response to carbon dioxide in man. Q J Exp Physiol Cogn Med Sci. 1958 Apr;43(2):214–227. doi: 10.1113/expphysiol.1958.sp001319. [DOI] [PubMed] [Google Scholar]
- LOESCHCHKE H. H., GERTZ K. H. Einfluss des O2-Druckes in der Einatmungsluft auf die Atemtätigkeit des Menschen, geprüft unter Konstanthaltung des alveolaren CO2-Druckes. Pflugers Arch. 1958;267(5):460–477. doi: 10.1007/BF00361733. [DOI] [PubMed] [Google Scholar]
- Lahiri S., Cherniack N. S., Edelman N. H., Fishman A. P. Regulation of respiration in goat and its adaptation to chronic and life-long hypoxia. Respir Physiol. 1971 Aug;12(3):388–403. doi: 10.1016/0034-5687(71)90079-x. [DOI] [PubMed] [Google Scholar]
- Lahiri S., DeLaney R. G. Relationship between carotid chemoreceptor activity and ventilation in the cat. Respir Physiol. 1975 Sep;24(3):267–286. doi: 10.1016/0034-5687(75)90018-3. [DOI] [PubMed] [Google Scholar]
- Lai Y. L., Tsuya Y., Hildebrandt J. Ventilatory responses to acute CO2 exposure in the rat. J Appl Physiol Respir Environ Exerc Physiol. 1978 Oct;45(4):611–618. doi: 10.1152/jappl.1978.45.4.611. [DOI] [PubMed] [Google Scholar]
- Lee L. Y., Milhorn H. T., Jr Central ventilatory responses to O2 and CO2 at three levels of carotid chemoreceptor stimulation. Respir Physiol. 1975 Dec;25(3):319–333. doi: 10.1016/0034-5687(75)90007-9. [DOI] [PubMed] [Google Scholar]
- Lundberg D., Breese G. R., Mueller R. A. Dopaminergic interaction with the respiratory control system in the rat. Eur J Pharmacol. 1979 Feb 15;54(1-2):153–159. doi: 10.1016/0014-2999(79)90417-5. [DOI] [PubMed] [Google Scholar]
- Maskrey M., Megirian D., Nicol S. C. Effects of decortication and carotid sinus nerve section on ventilation of the rat. Respir Physiol. 1981 Mar;43(3):263–273. doi: 10.1016/0034-5687(81)90108-0. [DOI] [PubMed] [Google Scholar]
- Maskrey M., Nicol S. C. The respiratory frequency response to carbon dioxide inhalation in conscious rabbits. J Physiol. 1980 Apr;301:49–58. doi: 10.1113/jphysiol.1980.sp013187. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Milic-Emili J., Grunstein M. M. Drive and timing components of ventilation. Chest. 1976 Jul;70(1 Suppl):131–133. doi: 10.1378/chest.70.1_supplement.131. [DOI] [PubMed] [Google Scholar]
- Mines A. H., Sorensen S. C. Ventilatory responses of awake normal goats during acute and chronic hypoxia. J Appl Physiol. 1970 Jun;28(6):826–831. doi: 10.1152/jappl.1970.28.6.826. [DOI] [PubMed] [Google Scholar]
- Mitchell R. A., Bainton C. R., Edelist G. Posthyperventilation apnea in awake dogs during metabolic acidosis and hypoxia. J Appl Physiol. 1966 Jul;21(4):1363–1367. doi: 10.1152/jappl.1966.21.4.1363. [DOI] [PubMed] [Google Scholar]
- NIELSEN M., SMITH H. Studies on the regulation of respiration in acute hypoxia; with a appendix on respiratory control during prolonged hypoxia. Acta Physiol Scand. 1952 Feb 12;24(4):293–313. doi: 10.1111/j.1748-1716.1952.tb00847.x. [DOI] [PubMed] [Google Scholar]
- Olson E. B., Jr, Dempsey J. A. Rat as a model for humanlike ventilatory adaptation to chronic hypoxia. J Appl Physiol Respir Environ Exerc Physiol. 1978 May;44(5):763–769. doi: 10.1152/jappl.1978.44.5.763. [DOI] [PubMed] [Google Scholar]
- Ou L. C., Tenney S. M. Hypoxia and carbon dioxide as separate and interactive depressants of ventilation. Respir Physiol. 1976 Dec;28(3):347–358. doi: 10.1016/0034-5687(76)90029-3. [DOI] [PubMed] [Google Scholar]
- Ou L. C., Tenney S. M. The role of brief hypocapnia in the ventilatory response to CO2 with hypoxia. Respir Physiol. 1976 Dec;28(3):333–346. doi: 10.1016/0034-5687(76)90028-1. [DOI] [PubMed] [Google Scholar]
- Palecek F., Chválová M., Novenko J. The influence of body temperature on the ventilatory response to CO 2 in anaesthetized rats. Acta Neurobiol Exp (Wars) 1973;33(1):155–161. [PubMed] [Google Scholar]
- Palecek F., Chválová M. Pattern of breathing in the rat. Physiol Bohemoslov. 1976;25(2):159–166. [PubMed] [Google Scholar]
- Pappenheimer J. R. Sleep and respiration of rats during hypoxia. J Physiol. 1977 Mar;266(1):191–207. doi: 10.1113/jphysiol.1977.sp011763. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Phillipson E. A., Hickey R. F., Bainton C. R., Nadel J. A. Effect of vagal blockade on regulation of breathing in conscious dogs. J Appl Physiol. 1970 Oct;29(4):475–479. doi: 10.1152/jappl.1970.29.4.475. [DOI] [PubMed] [Google Scholar]
- Richardson P. S., Widdicombe J. G. The role of the vagus nerves in the ventilatory responses to hypercapnia and hypoxia in anaesthetized and unanaesthetized rabbits. Respir Physiol. 1969 Jun;7(1):122–135. doi: 10.1016/0034-5687(69)90073-5. [DOI] [PubMed] [Google Scholar]
- Sahn S. A., Zwillich C. W., Dick N., McCullough R. E., Lakshminarayan S., Weil J. V. Variability of ventilatory responses to hypoxia and hypercapnia. J Appl Physiol Respir Environ Exerc Physiol. 1977 Dec;43(6):1019–1025. doi: 10.1152/jappl.1977.43.6.1019. [DOI] [PubMed] [Google Scholar]
- Stahl W. R. Scaling of respiratory variables in mammals. J Appl Physiol. 1967 Mar;22(3):453–460. doi: 10.1152/jappl.1967.22.3.453. [DOI] [PubMed] [Google Scholar]
- Székely M. The effect of hypoxia and hypercapnia on oxygen consumption and body temperature of rats treated with large doses of thyroxine. Acta Physiol Acad Sci Hung. 1970;37(1):57–63. [PubMed] [Google Scholar]
- Tenney S. M., Brooks J. G., 3rd Carotid bodies, stimulus interaction, and ventilatory control in unanesthetized goats. Respir Physiol. 1966;1(2):211–224. doi: 10.1016/0034-5687(66)90018-1. [DOI] [PubMed] [Google Scholar]
- Weiss H. R., Cohen J. A., McPherson L. A. Blood flow and relative tissue PO2 of brain and muscle: effect of various gas mixtures. Am J Physiol. 1976 Mar;230(3):839–844. doi: 10.1152/ajplegacy.1976.230.3.839. [DOI] [PubMed] [Google Scholar]
- YAMAMOTO W. S., EDWARDS M. W., Jr Homeostasis of carbon dioxide during intravenous infusion of carbon dioxide. J Appl Physiol. 1960 Sep;15:807–818. doi: 10.1152/jappl.1960.15.5.807. [DOI] [PubMed] [Google Scholar]
- von Euler C., Wexler I., Herrero F. Control mechanisms determining rate and depth of respiratory movements. Respir Physiol. 1970 Jul;10(1):93–108. doi: 10.1016/0034-5687(70)90030-7. [DOI] [PubMed] [Google Scholar]