title: Effects of hypoxia on urinary organic acid and hypoxanthine excretion in fetal sheep.
abstract: Severe birth asphyxia leads to a transient organic aciduria and increased hypoxanthine excretion. To investigate its origin and timing, we analyzed urine from 12 late gestation fetal sheep in utero subjected to moderately severe isocapnic hypoxia for 1 h. In six fetuses the carotid sinus nerves were cut to determine whether reflex peripheral vasoconstriction contributed to the changes in excretion. After a control period of 1 h, maternal inspired oxygen was reduced for 1 h so that fetal arterial oxygen tension fell significantly from 2.86 +/- 0.12 kPa (mean +/- SEM) to 1.55 +/- 0.04 kPa. The ewes were returned to normoxia, and monitoring was continued for 1 h. Fetal heart rate, arterial blood pressure, and femoral arterial blood flow (intact fetuses only) were recorded, and arterial pH, blood gases, and lactate were measured. Urine collected via a bladder catheter was analyzed for organic acids and hypoxanthine with gas chromatography-mass spectrometry. In intact fetuses, hypoxia increased excretion of hypoxanthine and several organic acids, notably lactic acid and intermediates of valine catabolism. Changes were apparent by 15 min, significant by 45 min, and maximal after reoxygenation. In denervated fetuses, there were small, significant, increases in organic acids and hypoxanthine by 45 min of hypoxia, but there was no surge in excretion posthypoxia. Hypoxia caused a large, significant, fall in femoral arterial blood flow in intact fetuses. We conclude that the extent of the reflex peripheral vasoconstriction, particularly in skeletal muscle, determines the amount of organic acid and hypoxanthine excretion and may explain similar biochemical disturbances after birth asphyxia. Urinary lactic acid measurement has a potential value for grading birth asphyxia.
authors.affiliation: Department of Chemical Pathology, Southampton General Hospital, United Kingdom.
authors.forename: V
authors.initials: V
authors.lastname: Walker
authors.forename: L
authors.initials: L
authors.lastname: Bennet
authors.forename: G A
authors.initials: GA
authors.lastname: Mills
authors.forename: L R
authors.initials: LR
authors.lastname: Green
authors.forename: K
authors.initials: K
authors.lastname: Gnanakumaran
authors.forename: M A
authors.initials: MA
authors.lastname: Hanson
mesh_terms: D000818:Animals; D001238:Asphyxia Neonatorum / Q000652:urine*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D002264:Carboxylic Acids / Q000652:urine*; D004195:Disease Models, Animal; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005865:Gestational Age; D006340:Heart Rate, Fetal / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019271:Hypoxanthine / Q000652:urine*; D000860:Hypoxia / Q000652:urine*; D007231:Infant, Newborn; D019344:Lactic Acid / Q000097:blood; D011247:Pregnancy; D012756:Sheep
chemical_list: D002264:Carboxylic Acids; D019271:Hypoxanthine; D019344:Lactic Acid