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. 1997 Mar 1;499(Pt 2):543–550. doi: 10.1113/jphysiol.1997.sp021947

Long-term facilitation of ventilation following repeated hypoxic episodes in awake goats.

D L Turner 1, G S Mitchell 1
PMCID: PMC1159325  PMID: 9080380

Abstract

1. This study tested two hypotheses: (1) that episodic hypoxia elicits long-term facilitation (LTF) in respiratory neurons that is manifest as an increase in ventilation in awake goats; and (2) that LTF causes complex changes in respiratory pattern which are responsible for the increase in ventilation. 2. Each goat participated in two protocols. In the first, inspired gas mixtures were alternated between isocapnic normoxia and hypoxia (arterial partial pressure of oxygen, Pa,O2 = 47 mmHg) for ten cycles. Each hypoxic episode lasted 3 min and normoxic intervals were 5 min. Ventilatory variables were measured during the last minute of each episode and periodically for up to 1 h following the last hypoxic episode. The second, sham protocol was undertaken at least 2 weeks later and was identical to the first, except that isocapnic hypoxia was replaced with normoxia. 3. Inspired ventilation (VI) increased during the first isocapnic hypoxic episode and reached progressively higher levels in subsequent hypoxic episodes. VI also increased progressively among normoxic intervals, such that by the tenth normoxic interval, it had increased 68% relative to the comparable sham value (P < 0.05). Respiratory frequency (FR), tidal volume and mean inspiratory flow all contributed to the augmented VI during both isocapnic normoxia and hypoxia. The increase in VI lasted up to 40 min after the final hypoxic episode, with an increased FR making the greatest contribution. The persistent increase in VI strongly suggests that episodic hypoxia elicits LTF in respiratory neurons in the awake goat. Complex changes in respiratory pattern underpin the ventilatory manifestation of LTF.

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Selected References

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  1. Bach K. B., Mitchell G. S. Hypoxia-induced long-term facilitation of respiratory activity is serotonin dependent. Respir Physiol. 1996 Jul;104(2-3):251–260. doi: 10.1016/0034-5687(96)00017-5. [DOI] [PubMed] [Google Scholar]
  2. Brodin E., Linderoth B., Goiny M., Yamamoto Y., Gazelius B., Millhorn D. E., Hökfelt T., Ungerstedt U. In vivo release of serotonin in cat dorsal vagal complex and cervical ventral horn induced by electrical stimulation of the medullary raphe nuclei. Brain Res. 1990 Dec 10;535(2):227–236. doi: 10.1016/0006-8993(90)91605-g. [DOI] [PubMed] [Google Scholar]
  3. Cao K. Y., Zwillich C. W., Berthon-Jones M., Sullivan C. E. Increased normoxic ventilation induced by repetitive hypoxia in conscious dogs. J Appl Physiol (1985) 1992 Nov;73(5):2083–2088. doi: 10.1152/jappl.1992.73.5.2083. [DOI] [PubMed] [Google Scholar]
  4. Engwall M. J., Bisgard G. E. Ventilatory responses to chemoreceptor stimulation after hypoxic acclimatization in awake goats. J Appl Physiol (1985) 1990 Oct;69(4):1236–1243. doi: 10.1152/jappl.1990.69.4.1236. [DOI] [PubMed] [Google Scholar]
  5. Engwall M. J., Daristotle L., Niu W. Z., Dempsey J. A., Bisgard G. E. Ventilatory afterdischarge in the awake goat. J Appl Physiol (1985) 1991 Oct;71(4):1511–1517. doi: 10.1152/jappl.1991.71.4.1511. [DOI] [PubMed] [Google Scholar]
  6. Erickson J. T., Millhorn D. E. Fos-like protein is induced in neurons of the medulla oblongata after stimulation of the carotid sinus nerve in awake and anesthetized rats. Brain Res. 1991 Dec 13;567(1):11–24. doi: 10.1016/0006-8993(91)91430-9. [DOI] [PubMed] [Google Scholar]
  7. Grahn D. A., Heller H. C. Activity of most rostral ventromedial medulla neurons reflect EEG/EMG pattern changes. Am J Physiol. 1989 Dec;257(6 Pt 2):R1496–R1505. doi: 10.1152/ajpregu.1989.257.6.R1496. [DOI] [PubMed] [Google Scholar]
  8. Hayashi F., Coles S. K., Bach K. B., Mitchell G. S., McCrimmon D. R. Time-dependent phrenic nerve responses to carotid afferent activation: intact vs. decerebellate rats. Am J Physiol. 1993 Oct;265(4 Pt 2):R811–R819. doi: 10.1152/ajpregu.1993.265.4.R811. [DOI] [PubMed] [Google Scholar]
  9. Holtman J. R., Jr, Vascik D. S., Maley B. E. Ultrastructural evidence for serotonin-immunoreactive terminals contacting phrenic motoneurons in the cat. Exp Neurol. 1990 Sep;109(3):269–272. doi: 10.1016/s0014-4886(05)80016-0. [DOI] [PubMed] [Google Scholar]
  10. McEvoy R. D., Popovic R. M., Saunders N. A., White D. P. Effects of sustained and repetitive isocapnic hypoxia on ventilation and genioglossal and diaphragmatic EMGs. J Appl Physiol (1985) 1996 Aug;81(2):866–875. doi: 10.1152/jappl.1996.81.2.866. [DOI] [PubMed] [Google Scholar]
  11. Millhorn D. E., Eldridge F. L., Waldrop T. G. Prolonged stimulation of respiration by endogenous central serotonin. Respir Physiol. 1980 Dec;42(3):171–188. doi: 10.1016/0034-5687(80)90113-9. [DOI] [PubMed] [Google Scholar]
  12. Mitchell G. S. Ventilatory control during exercise with increased respiratory dead space in goats. J Appl Physiol (1985) 1990 Aug;69(2):718–727. doi: 10.1152/jappl.1990.69.2.718. [DOI] [PubMed] [Google Scholar]
  13. Olson E. B., Jr Ventilatory adaptation to hypoxia occurs in serotonin-depleted rats. Respir Physiol. 1987 Aug;69(2):227–235. doi: 10.1016/0034-5687(87)90029-6. [DOI] [PubMed] [Google Scholar]
  14. Pilowsky P. M., de Castro D., Llewellyn-Smith I., Lipski J., Voss M. D. Serotonin immunoreactive boutons make synapses with feline phrenic motoneurons. J Neurosci. 1990 Apr;10(4):1091–1098. doi: 10.1523/JNEUROSCI.10-04-01091.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pizarro J., Ryan M. L., Hedrick M. S., Xue D. H., Keith I. M., Bisgard G. E. Intracarotid substance P infusion inhibits ventilation in the goat. Respir Physiol. 1995 Jul;101(1):11–22. doi: 10.1016/0034-5687(95)00015-6. [DOI] [PubMed] [Google Scholar]
  16. Ryan M. L., Hedrick M. S., Pizarro J., Bisgard G. E. Carotid body noradrenergic sensitivity in ventilatory acclimatization to hypoxia. Respir Physiol. 1993 Apr;92(1):77–90. doi: 10.1016/0034-5687(93)90121-p. [DOI] [PubMed] [Google Scholar]
  17. Veasey S. C., Fornal C. A., Metzler C. W., Jacobs B. L. Response of serotonergic caudal raphe neurons in relation to specific motor activities in freely moving cats. J Neurosci. 1995 Jul;15(7 Pt 2):5346–5359. doi: 10.1523/JNEUROSCI.15-07-05346.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Voss M. D., De Castro D., Lipski J., Pilowsky P. M., Jiang C. Serotonin immunoreactive boutons form close appositions with respiratory neurons of the dorsal respiratory group in the cat. J Comp Neurol. 1990 May 8;295(2):208–218. doi: 10.1002/cne.902950205. [DOI] [PubMed] [Google Scholar]

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