Abstract
Rises in fetal adenosine during hypoxia may have a metabolic inhibitory role that helps the fetus adapt to periods of low arterial partial pressure of oxygen (Pao2). We examined the fetal cerebral hemodynamic and metabolic responses to exogenous adenosine infusion and compared this with previous studies. Six fetal sheep at ca. 125 d gestation were instrumented under general anesthesia with catheters, flow probes, and near-infrared optodes and allowed to recover. After 3 d, adenosine was infused at a level known to reproduce fetal levels during hypoxia. Fetal hemodynamics and cerebral near-infrared spectroscopic (NIRS) variables were monitored and paired blood samples taken for oxygen delivery and consumption calculation. Fetal heart rate, mean arterial pressure, and carotid flow showed no change during adenosine infusion. Cerebral oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), and blood volume rose, suggesting venous pooling in the brain. Cerebral cytochrome oxidase (CcO) became more oxidized, indicating reduction in electron flow down the mitochondrial electron transfer chain and, thus, a fall in metabolic rate. Blood sample analysis revealed that there was no change in oxygen delivery to the head but that cerebral oxygen consumption fell during adenosine infusion. These data indicate that fetal cerebral metabolism fell during infusion of adenosine at a level known to reproduce fetal plasma concentrations during hypoxia.
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Abbreviations
- CaBF:
-
carotid artery blood flow
- CBV:
-
cerebral blood volume
- CcO:
-
oxidized cytochrome oxidase
- CuA:
-
copper A moiety of cytochrome oxidase
- DO2:
-
oxygen delivery
- Hb:
-
deoxyhemoglobin
- HbO2:
-
oxyhemoglobin
- NO:
-
nitric oxide
- Pao2:
-
arterial Po2
- tHb:
-
total Hb
- V˙o2:
-
oxygen consumption
References
Sawa R, Asakura H, Power GG 1991 Changes in plasma adenosine during simulated birth of fetal sheep. J Appl Physiol 70: 1524–1528
Kubonoya K, Power GG 1997 Plasma adenosine responses during repeated episodes of umbilical cord occlusion. Am J Obstet Gynecol 177: 395–401
Yoneyama Y, Wakatsuki M, Sawa R, Kamoi S, Takahashi H, Shin S, Kawamura T, Power GG, Araki T 1994 Plasma adenosine concentration in appropriate- and small-for-gestational-age fetuses. Am J Obstet Gynecol 170: 684–688
Rudolphi KA, Schubert P, Parkinson FE, Fredholm BB 1992 Neuroprotective role of adenosine in cerebral ischaemia. Trends Pharmacol Sci 13: 439–445
Gidday JM, Fitzgibbons JC, Shah AR, Kraujalis MJ, Park TS 1995 Reduction in cerebral ischemic injury in the newborn rat by potentiation of endogenous adenosine. Pediatr Res 38: 306–311
Kurth CD, Wagerle LC 1992 Cardiovascular reactivity to adenosine analogues in 0.6–0.7 gestation and near-term fetal sheep. Am J Physiol 262: H1338–H1342
Laudignon N, Farri E, Beharry K, Rex J, Aranda JV 1990 Influence of adenosine on cerebral blood flow during hypoxic hypoxia in the newborn piglet. J Appl Physiol 68: 1534–1541
Karimi A, Ball KT, Power GG 1996 Exogenous infusion of adenosine depresses whole body O2 use in fetal/neonatal sheep. J Appl Physiol 81: 541–547
de Mendonca A, Ribeiro JA 1993 Adenosine inhibits the NMDA receptor-mediated excitatory postsynaptic potential in the hippocampus. Brain Res 606: 351–356
Newman JP, Peebles DM, Harding SRG, Springett R, Hanson MA 2000 Hemodynamic and metabolic responses to moderate asphyxia in brain and skeletal muscle of late-gestation fetal sheep. J Appl Physiol 88: 82–90
Matcher SJ, Elwell CE, Cooper CE, Cope M, Delpy DT 1995 Performance comparison of several published tissue near-infrared spectroscopic algorithms. Anal Biochem 227: 54–68
Wray S, Cope M, Delpy DT, Wyatt JS, Reynolds EOR 1988 Characterisation of the near infrared absorption spectra of cytochrome aa3 and haemoglobin for the noninvasive monitoring of cerebral oxygenation. Biochim Biophys Acta 933: 184–192
Cooper CE, Elwell CE, Meek JH, Matcher SJ, Wyatt JS, Cope M, Delpy DT 1996 The noninvasive measurement of absolute cerebral deoxyhemoglobin concentration and mean optical path length in the neonatal brain by second derivative near infrared spectroscopy. Pediatr Res 39: 32–38
Ongini E, Adami M, Ferri C, Bertoerelli R 1997 Adenosine A2A receptors and neuroprotection. Ann N Y Acad Sci 825: 30–48
Koos BJ, Chau A 1998 Fetal cardiovascular and breathing responses to an adenosine A2 receptor agonist in sheep. Am J Physiol 274: R152–R159
Marks KA, Mallard CE, Roberts I, Williams CE, Gluckman PD, Edwards AD 1996 Nitric oxide synthase inhibition attenuates delayed vasodilation and increases injury after cerebral ischemia in fetal sheep. Pediatr Res 40: 185–191
Kamii H, Mikawa S, Murakami K, Kinouchi H, Yoshimoto T, Reola L, Carlson E, Epstein CJ, Chan PH 1996 Effects of nitric oxide synthase inhibition on brain infarction in SOD-1-transgenic mice following transient focal cerebral ischemia. J Cereb Blood Flow Metab 16: 1153–1157
Kawahara N, Ide T, Saito N, Kawai K, Kirino T 1998 Propentofylline potentiates induced ischemic tolerance in gerbil hippocampal neurons via adenosine receptor. J Cereb Blood Flow Metab 18: 472–475
Koos BJ, Doany W 1991 Role of plasma adenosine in breathing responses to hypoxia in fetal sheep. J Dev Physiol 16: 81–85
Rurak DW, Gruber NG 1983 The effect of neuromuscular blockade on oxygen consumption and blood gases in the fetal lamb. J Dev Physiol 145: 258–262
Dolphin AC, Archer ER 1983 An adenosine agonist inhibits and a cyclic AMP analogue enhances the release of glutamate but not GABA from slices of rat dentate gyrus. Neurosci Lett 43: 49–54
Corradetti R, Lo Conte G, Moroni F, Passani MB, Pepeu G 1984 Adenosine decreases aspartate and glutamate release from rat hippocampal slices. Eur J Pharmacol 104: 19–26
Dunwiddie TV, Fredholm BB 1989 Adenosine A1 receptors inhibit adenylate cyclase activity and neurotransmitter release and hyperpolarize pyramidal neurons in rat hippocampus. J Pharmacol Exp Ther 249: 31–37
Cooper CE, Springett R 1997 Measurement of cytochrome oxidase and mitochondrial energetics by near-infrared spectroscopy. Philos Trans R Soc Lond 352: 669–676
Janigro D, Wender R, Ransom G, Tinklepaugh DL, Winn HR 1996 Adenosine-induced release of nitric oxide from cortical astrocytes. Neuroreport 7: 1640–1644
Brown CG 1999 Nitric oxide and mitochondrial respiration. Biochim Biophys Acta 1411: 351–369
Clementi E, Brown CG, Feelisch M, Moncada S 1998 Persistent inhibition of cell respiration by nitric oxide: crucial role of S-nitrosylation of mitochondrial complex I and protective action of glutathione. Proc Natl Acad Sci USA 95: 7631–7636
Clementi E, Brown CG, Foxwell N, Moncada S 1999 On the mechanism by which vascular endothelial cells regulate their oxygen consumption. Proc Natl Acad Sci USA 96: 1559–1562
Yager JY, Brucklacher RM, Vannucci RC 1996 Paradoxical mitochondrial oxidation in perinatal hypoxic-ischemic brain damage. Brain Res 712: 230–238
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Newman, J., Peebles, D. & Hanson, M. Adenosine Produces Changes in Cerebral Hemodynamics and Metabolism as Assessed by Near-Infrared Spectroscopy in Late-Gestation Fetal Sheep in Utero. Pediatr Res 50, 217–221 (2001). https://doi.org/10.1203/00006450-200108000-00009
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DOI: https://doi.org/10.1203/00006450-200108000-00009
