Journal of Applied Physiology, Vol 77, Issue 6 2734-2739, Copyright © 1994 by American Physiological Society

ARTICLES

Hypoxic inhibition of breathing in fetal sheep: relationship to brain adenosine concentrations

B. J. Koos, B. A. Mason, O. Punla and A. M. Adinolfi
Nicholas S. Assali Perinatal Research Laboratory, Department of Obstetrics and Gynecology, University of California, Los Angeles School of Medicine 90024.

Because hypoxic inhibition of fetal breathing may be caused by a rise in central adenosine levels, the effects of O2 deficiency on fetal brain adenosine concentrations were determined at levels of hypoxia that inhibited fetal breathing. Under halothane anesthesia, the brains of fetal sheep (0.8 term) were implanted with guide cannulas exteriorized through a Silastic rubber window in the uterus and flank of the ewe. At least 4 days after surgery, a microdialysis probe was inserted into a cannula with the membrane tip placed in the rostral brain stem. During 1 h of isocapnic hypoxia, mean fetal arterial PO2 was reduced from 24.0 +/- 0.9 Torr (control) to 13 +/- 0.6 Torr and arterial pH fell progressively from 7.354 +/- 0.007 to 7.273 +/- 0.023. Hypoxia decreased the incidence of fetal breathing movements from 33 +/- 5.2 to 5 +/- 2.2 min/h, with a normal incidence (29 +/- 3.5 min/h) during the hour after arterial PO2 returned to control values. Adenosine concentrations in microdialysis perfusate under control conditions averaged approximately 35 nM, increased up to 2.3-fold during the hour of O2 deficiency, and fell toward control values when normoxia was restored. We conclude that fetal brain adenosine levels are increased at levels of O2 deficiency that inhibit fetal breathing, which are results consistent with a role for adenosine in hypoxic inhibition of fetal breathing.

This article has been cited by other articles:

				C. C. Wendler, M. Busovsky-McNeal, S. Ghatpande, A. Kalinowski, K. S. Russell, and S. A. Rivkees Embryonic caffeine exposure induces adverse effects in adulthood FASEB J, April 1, 2009; 23(4): 1272 - 1278. [Abstract] [Full Text] [PDF]

				T. Maeda and B. J. Koos Adenosine A1 and A2a receptors modulate insulinemia, glycemia, and lactatemia in fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2009; 296(3): R693 - R701. [Abstract] [Full Text] [PDF]

				W. Pearce Hypoxic regulation of the fetal cerebral circulation J Appl Physiol, February 1, 2006; 100(2): 731 - 738. [Abstract] [Full Text] [PDF]

				K. Ballanyi Protective role of neuronal KATP channels in brain hypoxia J. Exp. Biol., August 15, 2004; 207(18): 3201 - 3212. [Abstract] [Full Text] [PDF]

				A. B Blood, C. J Hunter, and G. G Power Adenosine mediates decreased cerebral metabolic rate and increased cerebral blood flow during acute moderate hypoxia in the near-term fetal sheep J. Physiol., December 15, 2003; 553(3): 935 - 945. [Abstract] [Full Text] [PDF]

				A. B Blood, C. J Hunter, and G. G Power The role of adenosine in regulation of cerebral blood flow during hypoxia in the near-term fetal sheep J. Physiol., September 15, 2002; 543(3): 1015 - 1023. [Abstract] [Full Text] [PDF]

				P. M. de Paula and B. H. Machado Antagonism of adenosine A1 receptors in the NTS does not affect the chemoreflex in awake rats Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2001; 281(6): R2072 - R2078. [Abstract] [Full Text] [PDF]

				B. J. Koos, T. Maeda, and C. Jan Adenosine A1 and A2A receptors modulate sleep state and breathing in fetal sheep J Appl Physiol, July 1, 2001; 91(1): 343 - 350. [Abstract] [Full Text] [PDF]

				J. M. Bissonnette Mechanisms regulating hypoxic respiratory depression during fetal and postnatal life Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2000; 278(6): R1391 - R1400. [Abstract] [Full Text] [PDF]

				B. J. Koos, A. Chau, M. Matsuura, O. Punla, and L. Kruger Thalamic lesions dissociate breathing inhibition by hypoxia and adenosine in fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2000; 278(4): R831 - R837. [Abstract] [Full Text] [PDF]

				C. S. Watson, S. E. White, J. H. Homan, L. Fraher, J. F. Brien, and A. D. Bocking The adenosine A1-receptor antagonist 8-CPT reverses ethanol-induced inhibition of fetal breathing movements J Appl Physiol, October 1, 1999; 87(4): 1333 - 1338. [Abstract] [Full Text] [PDF]

				A. Chau and B. J. Koos Metabolic and cardiorespiratory responses to hypoxia in fetal sheep: adenosine receptor blockade Am J Physiol Regulatory Integrative Comp Physiol, June 1, 1999; 276(6): R1805 - R1811. [Abstract] [Full Text] [PDF]

				C. S. Watson, S. E. White, J. H. Homan, K. A. Kimura, J. F. Brien, L. Fraher, J. R. G. Challis, and A. D. Bocking Increased cerebral extracellular adenosine and decreased PGE2 during ethanol-induced inhibition of FBM J Appl Physiol, April 1, 1999; 86(4): 1410 - 1420. [Abstract] [Full Text] [PDF]

				B. J. Koos, A. Chau, M. Matsuura, O. Punla, and L. Kruger Thalamic Locus Mediates Hypoxic Inhibition of Breathing in Fetal Sheep J Neurophysiol, May 1, 1998; 79(5): 2383 - 2393. [Abstract] [Full Text] [PDF]