Factors limiting regeneration of ATP following temporary ischemia in cat brain.
Cerebral ischemia was induced in cats using bilateral carotid artery occlusion coupled with hemorrhagic hypotension. Thirty minutes of ischemia, which depleted levels of ATP and phosphocreatine throughout the cerebral cortex, was followed by 2-4 hours of recirculation. During the recovery period, cortical perfusion and NADH fluorescence were monitored through a cranial window. Postischemic perfusion, as indicated by transit time, was initially higher than control, but declined to subnormal levels by 60 minutes. NADH fluorescence transients, induced by brief anoxia, also decreased steadily during recirculation, indicating a failure of oxidation-reduction capability. The disappearance of anoxic-NADH transients usually preceded the decline of flow, suggesting that O2 delivery was not the factor limiting redox reactions. Furthermore, tissue levels of NADH, which were nearly normal after 2-4 hours of recirculation, did not indicate tissue hypoxia. In spite of normalization of NADH, resynthesis of high energy phosphates were severely impaired. The degree of ATP recovery varied widely in different cortical regions; however, there were two general groups of ATP values--one at 5% and the other at 70% of control levels. In the energy-depleted areas, NADH levels were normal, but the total pool of NAD (NADH + NAD+) and the tissue content of K+ were 43% lower than control. In contrast, the NAD pool and K+ content were only slightly diminished in the regions with greater ATP restitution. The results suggest that postischemic resynthesis of ATP may be limited not by inadequate delivery of O2, but rather by defective production of NADH.
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D001784:Blood Gas Analysis; D002415:Cats; D002540:Cerebral Cortex / Q000378:metabolism*; D002560:Cerebrovascular Circulation; D004734:Energy Metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D007773:Lactates / Q000096:biosynthesis; D019344:Lactic Acid; D009243:NAD / Q000096:biosynthesis; D010725:Phosphocreatine / Q000096:biosynthesis
D007773:Lactates; D010725:Phosphocreatine; D009243:NAD; D019344:Lactic Acid; D000255:Adenosine Triphosphate