Address of Corresponding Author

Med Princ Pract 2004;13:277-281 (DOI: 10.1159/000079527)

  Key Words

• Moderate hypoxia
• Hypoxic depression of ventilation
• Theophylline

  Abstract

Objective: The present study was undertaken to investigate the ventilatory response due to sustained isocapnic moderate hypoxia and the possible role of adenosine in hypoxic depression in anesthetized cats. Materials and Methods: Cats anesthetized with pentothal sodium (30 mg kg^-1 i.p.) were divided into two groups: treated (n = 11) and control (n = 15). Respiratory frequency (f), tidal volume (V_T), minute volume (E) and systemic arterial blood pressure were recorded during air and 20 min of breathing hypoxic gas mixture (14% O₂-86% N₂). Isocapnia was maintained by adding fractions of 1% CO₂ to the inspired hypoxic gas mixture. The PaO₂ and PaCO₂ were determined. Results: On hypoxic gas mixture breathing, V_T and E values of the control animals increased significantly, at 5 min to 50 ± 6 and 53 ± 6%, respectively, above the prehypoxic air phase value (p < 0.001). After that, the magnitude of increase in V_T and E declined gradually. At 20 min of hypoxia, V_T and E were less than those in prehypoxic air phase (17 ± 7, 16 ± 7%, respectively). In cats injected with an adenosine antagonist (theophylline 13.6 mg kg^-1 i.v.), f, V_T and E increased significantly at 5 min of hypoxia (p < 0.001). At 20 min of hypoxia, f, V_T and E were 8 ± 2, 30 ± 8, and 39 ± 8%, respectively, higher than corresponding values of the prehypoxic stage. In cats injected with theophylline (0.5 mg kg^-1) by cisternal puncture V_T and E increased significantly at 5 min of hypoxia. At 20 min of hypoxia, V_T and E were 27 ± 7 and 31 ± 8% higher than those in the prehypoxic air phase. Conclusion: The results of this study show that accumulation of adenosine in the brain during hypoxia seems to reduce the response of the central mechanisms to chemoreceptor impulses.

Copyright © 2004 S. Karger AG, Basel

  References

1.

Beckenbosh A, De Gioede J: Effects of brain hypoxia on ventilation. Eur Respir J 1988;1:184-190.

2.

Wenging L, Lobchuk D, Anthonisen NR: Ventilatory response to CO₂ and hypoxia after sustained hypoxia in awake cats. J Appl Physiol 1994;76:2262-2266.

3.

Wenging L, Giesbrech GG, Anthonisen NR: Ventilatory response to moderate hypoxia in awake chemodenervated cats. J Appl Physiol 1993;74:805-810.

4.

Vizek M, Pickett KC, Weil VJ: Biphasic ventilatory response of adult cats to sustained hypoxia has central origin. J Appl Physiol 1987;63:1658-1664.

5.

Neubauer JA, Melton JE, Edelman NH: Modulation of respiration during brain hypoxia. J Appl Physiol 1990;68:441-451.

6.

Miller MJ, Tenney SM: Hypoxia-induced tachypnea in carotid deafferented cats. Respir Physiol 1975;23:31-39.

7.

Oruç T: The activation of central and peripheral respiratory control mechanisms in hyperoxia and hypoxia. Bull Eur Physiopathol Respir 1982;18:113.

8.

Oruç T, Terziolu M, ahin G, Dursun S: Response of the central respiratory control mechanisms to hyperoxia and hypoxia. Bull Eur Physiopathol Respir 1982;18:439-447.

9.

van Beek JH, Beckenbosh A, De Goede J, Oliever CN: Effects of brainstem hypoxaemia on the regulation of breathing. Respir Physiol 1984;57:171-189.

10.

van Beek JH, Beckenbosh A, Oliever CN, Quanger PhH: Depression of ventilation during brainstem hypoxia in anesthetized cats. Bull Eur Physiopathol Respir 1982;18:139-144.

11.

Oliever CN, Beckenbosch A, Beek van JH, De Coede J, Quanjer Ph H: Hypoxia, cerebrospinal fluid PCO₂ and central depression of ventilation. Bull Eur Physiopathol Respir 1982;18:165-172.

12.

Soto-Arape I, Burton MD, Kazemi H: Central amino acid neurotransmitters and the hypoxic ventilatory response. Am J Respir Crit Care Med 1995;151:1113-1120.

13.

Richter DW, Schmidt-Garcon P, Pierrefiche O, Bischoft AM, Lalley PM: Brainstem amino acid neurotransmitters and hypoxic ventilatory response. J Physiol 1999;514:567-578.

14.

Melton JE, Neubauer JA, Edelman NH: GABA antagonism reverses hypoxic respiratory depression in the cat. J Appl Physiol 1990;69:1296-1301.

15.

Güner I, Yelmen N, ahin G, Oruc T: The effect of intracerebroventricular dopamine administration on the respiratory response to hypoxia. Tohoku J Exp Med 2002;196:219-230.

16.

Eldridge FL, Milhorn DE, Kiley JP: Antagonism by theophylline of respiratory inhibition induced by adenosine. J Appl Physiol 1985;59:1428-1433.

17.

Javaheri S, Teppema LJ, Evers JA: Effects of aminophylline on hypoxemia induced ventilatory depression in the cat. J Appl Physiol 1988;64:1837-1843.

18.

ahin G, Terziolu M: The influence of chronic hypoxia on erythrocytic 2,3-diphosphoglycerate and the sensitivity of peripheral chemoreceptors of rabbits. Cerrahpaa Med Rev 1985;4:46-56.

19.

Eldridge FL, Millhorn DE, Waldrop TG, Kiley JP: Mechanism of respiratory effects of methylxanthines. Respir Physiol 1983;53:239-261.

20.

Lincoln TM, Cornwell TL, Taylor A: c-GMP-dependent protein kinase mediates the reduction of Ca²⁺ by cAMP in vascular smooth muscle cells. Am J Physiol 1990;259:399-407.

21.

Scislo TJ, O'Leary DS: Mechanisms mediating regional sympathoactivatory responses to stimulation of NTS A(1) adenosine receptors. Am J Physiol Heart Circ Physiol 2002;283:H1588-H1599.

  Author Contacts

Nermin Karaturan Yelmen
Department of Physiology, Cerrahpaa Faculy of Medicine
Istanbul University
TR-34303 Cerrahpaa, Istanbul (Turkey)
Tel. +90 212 414 30 71, Fax +90 212 414 30 72, E-Mail nermink@istanbul.edu.tr

  Article Information

Received: October 7, 2002
Revised: September 10, 2003
Number of Print Pages : 5
Number of Figures : 0, Number of Tables : 2, Number of References : 21

  Publication Details

Medical Principles and Practice
A Publication of the Academic Publications Council

Vol. 13, No. 5, Year 2004 (Cover Date: September-October 2004)

Journal Editor: Farida Al Awadi, Kuwait
ISSN: 1011-7571 (print), 1423-0151 (Online)

For additional information: http://www.karger.com/mpp

  Drug Dosage / Copyright

Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.