Exogenous infusion of adenosine depresses whole body O2 use in fetal/neonatal sheep.
To examine a possible metabolic regulatory role for adenosine, infusions of adenosine and adenosine deaminase were given to 11 near-term fetal sheep during the simulation of birth in utero. Fetal arterial blood gases, the concentration of a number of metabolites, insulin, and whole body O2 consumption (VO2) were measured. After intrauterine ventilation and cord occlusion, fetal/neonatal VO2, measured by closed-circuit respirometry, averaged 11.0 +/- 1.1 (SE) ml (STPD).min-1.kg fetal wt-1 and plasma adenosine concentration ([Ado]) was 1.29 +/- 0.21 microM. Infusion of adenosine (1.5 mumol.min-1.kg-1) during the next 30-min interval increased [Ado] to 1.57 +/- 0.28 microM (not significant) and decreased VO2 to 7.7 +/- 0.5 ml.min-1.kg-1 (P < 0.05). The infusion reduced systolic blood pressure by 19% (P < 0.01) and diastolic blood pressure by 25% (P < 0.01) and increased heart rate by 19% (P < 0.01). At the highest rate of adenosine infusion studied (6 mumol.min-1.kg-1), [Ado] increased to 4.27 +/- 0.46 microM (P < 0.001) and VO2 did not measurably decline further, although there were further decreases in blood pressure and increases in heart rate. After administration of adenosine deaminase, [Ado] decreased to 0.58 +/- 0.13 microM (P < 0.05), whereas VO2 increased to 11.2 +/- 0.8 ml.min-1.kg-1 (P < 0.05); blood pressure and heart rate returned to basal levels. The dependence of VO2 on [Ado] is described by the relationship VO2 = 6.14 + 4.89 exp(-0.45[Ado]) (n = 144; r = 0.34; P < 0.001). Throughout the experiment, arterial O2 content and plasma glucose, lactate, glycerol, and fatty acid concentrations were normal or elevated, and, therefore, O2 lack and substrate deficiency were unlikely to have caused the reduction in VO2. We conclude that plasma adenosine may act as a messenger of energy status for the ovine fetus/neonate and may contribute thereby to a maintenance of a balance between O2 supply and O2 demand.
Karimi
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A
Center for Perinatal Biology, Loma Linda University School of Medicine, California 92350, USA.
Ball
K T
KT
Power
G G
GG
D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D010101:Oxygen Consumption / Q000187:drug effects*; D011247:Pregnancy; D012756:Sheep
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D000243:Adenosine Deaminase; D000241:Adenosine