Brain metabolic correlates of hypoxic-ischemic cerebral necrosis in mid-gestational sheep fetuses: significance of hypotension.
Mid-gestational sheep fetuses exposed to marked hypoxia for 2 h remain brain intact if MABP is maintained above 30 mm Hg. On the other hand, similarly hypoxic fetuses, if they experience reductions in MABP below 30 mm Hg, develop foci of necrosis that predominantly affect hemispheric white matter and neostriatum. Cortex damage is more restricted and is usually associated with more massive underlying white matter damage. The present study examines the brain metabolic basis for the important role of hypotension in brain injury development in marked hypoxia. Sheep fetuses rendered hypoxic by respiring their ewes with 11% oxygen (fetal PaO2 = 8-12 mm Hg) in which MABP was maintained above 30 mm Hg showed increases in brain lactic acid concentrations to 7-13 mumol/g but unaltered energy charge. In contrast, fetuses that sustained MABP reductions below 30 mm Hg showed increases in lactic acid concentrations in vulnerable structures to 16-24 mumol/g accompanied by marked decreases in energy charge. The vulnerable structures also showed reductions in fructose concentrations but a variable behavior of other brain metabolites including phosphocreatine, glycogen, and glucose. Thus, the present findings suggest a relation between hypotension during marked hypoxia, low energy charge, lactic acid accumulation in brain at high concentrations, and fetal brain injury. The ewes of hypoxic hypotensive fetuses received pentobarbital at lower doses than did those of fetuses that maintained blood pressure. This suggests that pentobarbital plays an important role in protecting the fetal brain from asphyxia by extending the hypoxic fetus's ability to maintain blood pressure in addition to reducing its brain metabolism.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D004734:Energy Metabolism; D005260:Female; D005315:Fetal Diseases / Q000378:metabolism*; D007022:Hypotension / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000503:physiopathology; D009336:Necrosis; D010100:Oxygen / Q000097:blood; D010424:Pentobarbital / Q000008:administration & dosage; D011247:Pregnancy; D012756:Sheep
D010424:Pentobarbital; D010100:Oxygen