Fetal breathing movement, sleep state and cardiovascular responses to an inhibitor of mitochondrial ATPase in sheep.
Hypoxia abolishes breathing movements in fetal sheep, perhaps by reducing ATP synthesis within regulatory brain cells. This possibility was examined by administering to 13 chronically catheterized fetal sheep oligomycin B, a mitochondrial ATPase inhibitor. Injections into the left external carotid artery of oligomycin B (170 +/- 19 micrograms/kg in 9 fetuses) reduced significantly (P less than 0.01) the incidence of fetal breathing movements from a control mean of 52 +/- 6.3% to 6 +/- 2.2 and 9 +/- 4.4% during the first and second hours after drug injection. Oligomycin did not decrease significantly the incidence of low voltage electrocortical activity or reduce the average duration of a cycle of low and high voltage electrocortical states. Nor did it decrease significantly the incidence of rapid eye movements. Fetal heart rate and mean arterial pressure were not significantly affected, and the arterial blood gases and pH did not significantly differ from control values. However, a large dose of the drug (700 micrograms/kg) produced an isoelectric electrocorticogram, hypertension, and bradycardia associated with a rise in arterial PO2 and a severe metabolic acidosis. In 3 fetal sheep oligomycin also inhibited continuous breathing induced by indomethacin. Injection of the vehicle (ethanol) alone did not alter the incidence of breathing movements, electrocortical activity, eye movements or blood gases. These results suggest that reduced mitochondrial production of ATP may be a mechanism by which hypoxia abolishes fetal breathing activity.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D005333:Fetus / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D009840:Oligomycins / Q000494:pharmacology; D012119:Respiration / Q000187:drug effects; D012756:Sheep / Q000196:embryology*; D012890:Sleep / Q000502:physiology*
D009840:Oligomycins; C048335:oligomycin B; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases