Delayed neurologic deterioration following anoxia: brain mitochondrial and metabolic correlates.
Hyper- but not normoglycemic cats exposed to 8 min of anoxia show neurologic signs (fasciculations, myoclonic jerks, seizures) that develop after a symptom-free period. We examined brain mitochondrial function and metabolite concentrations at 0, 1, 3, and 5 h following exposure to anoxia, to correlate biochemical findings with the presence ("symptomatic") or absence ("presymptomatic") of neurologic signs. Brain mitochondria isolated postexposure only from symptomatic cats showed markedly decreased (-50%), state 3 (ADP-stimulated), and uncoupler-stimulated respiration rates with NAD- and FAD-linked substrates. Respiratory control and ADP/oxygen (ADP/O) ratios remained unchanged, indicating, respectively, that coupling and efficiency of ATP synthesis were preserved. Thus, inhibition of electron transport chain function, not phosphorylative activity, may be rate limiting for respiration. During anoxia, hyperglycemic cats showed higher brain lactate levels (26 versus 20 mumol/g), but similar ATP and phosphocreatine concentrations, compared with normoglycemic cats. After exposure, in all animals lactate and phosphocreatine were restored to control levels, whereas ATP remained at 85%. Cats that became symptomatic demonstrated four- to sixfold increases in lactate and 50% reductions in phosphocreatine. At 3 and 5 h postexposure, symptomatic animals showed significant reductions in ATP concentrations. We conclude that although initially asymptomatic, hyperglycemic cats exposed to anoxia undergo a neurologic deterioration over several hours following reoxygenation that is correlated with inhibition of mitochondrial respiration, increases in tissue lactate, and decreases in energy state.
Wagner
K R
KR
Medical Research Service, Veterans Administration Medical Center, Cincinnati, Ohio 45220.
Kleinholz
M
M
Myers
R E
RE
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002245:Carbon Dioxide / Q000378:metabolism; D002415:Cats; D003573:Cytochrome b Group / Q000378:metabolism; D005260:Female; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009929:Organ Size; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid
D001786:Blood Glucose; D003573:Cytochrome b Group; D005971:Glutamates; D007773:Lactates; D013386:Succinates; D010725:Phosphocreatine; D009243:NAD; D002245:Carbon Dioxide; D005182:Flavin-Adenine Dinucleotide; D019344:Lactic Acid; D018698:Glutamic Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D019802:Succinic Acid; D010100:Oxygen