title: Fetal in vivo continuous cardiovascular function during chronic hypoxia.
abstract: Although the fetal cardiovascular defence to acute hypoxia and the physiology underlying it have been established for decades, how the fetal cardiovascular system responds to chronic hypoxia has been comparatively understudied. We designed and created isobaric hypoxic chambers able to maintain pregnant sheep for prolonged periods of gestation under controlled significant (10% O2) hypoxia, yielding fetal mean P(aO2) levels (11.5 ± 0.6 mmHg) similar to those measured in human fetuses of hypoxic pregnancy. We also created a wireless data acquisition system able to record fetal blood flow signals in addition to fetal blood pressure and heart rate from free moving ewes as the hypoxic pregnancy is developing. We determined in vivo longitudinal changes in fetal cardiovascular function including parallel measurement of fetal carotid and femoral blood flow and oxygen and glucose delivery during the last third of gestation. The ratio of oxygen (from 2.7 ± 0.2 to 3.8 ± 0.8; P < 0.05) and of glucose (from 2.3 ± 0.1 to 3.3 ± 0.6; P < 0.05) delivery to the fetal carotid, relative to the fetal femoral circulation, increased during and shortly after the period of chronic hypoxia. In contrast, oxygen and glucose delivery remained unchanged from baseline in normoxic fetuses. Fetal plasma urate concentration increased significantly during chronic hypoxia but not during normoxia (Δ: 4.8 ± 1.6 vs. 0.5 ± 1.4 μmol l(-1), P<0.05). The data support the hypotheses tested and show persisting redistribution of substrate delivery away from peripheral and towards essential circulations in the chronically hypoxic fetus, associated with increases in xanthine oxidase-derived reactive oxygen species.
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: B J
authors.initials: BJ
authors.lastname: Allison
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: K L
authors.initials: KL
authors.lastname: Brain
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: Y
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: A D
authors.initials: AD
authors.lastname: Kane
authors.affiliation: Laboratorio de Función y Reactividad Vascular, Programa de Fisiopatología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
authors.forename: E A
authors.initials: EA
authors.lastname: Herrera
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.|Department of Radiology, Stanford University Medical Centre, Palo Alto, CA, 94305, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Thakor
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Botting
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: Cross
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: N
authors.initials: N
authors.lastname: Itani
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: K L
authors.initials: KL
authors.lastname: Skeffington
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: C
authors.initials: C
authors.lastname: Beck
authors.affiliation: Department of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
authors.forename: D A
authors.initials: DA
authors.lastname: Giussani
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis / Q000295:instrumentation / Q000379:methods*; D003326:Coronary Circulation; D005260:Female; D005318:Fetal Heart / Q000503:physiopathology*; D005311:Fetal Hypoxia / Q000503:physiopathology*; D006334:Heart Function Tests / Q000295:instrumentation / Q000379:methods*; D021041:Placental Circulation; D011247:Pregnancy; D058998:Remote Sensing Technology / Q000295:instrumentation / Q000379:methods*; D012756:Sheep