Metabolic heterogeneity in brain tissue during incomplete ischemia and reperfusion.
Two metabolically distinct cell populations were detected when two peaks of inorganic phosphate (Pi), corresponding to two pHi values, were recorded by Phosphorus Magnetic Resonance Spectroscopy (31P MRS). One cell population, having intracellular pH (pHi) values less than 6.3, was thought to contain neither PCr (phosphocreatine) nor ATP and was thus considered metabolically unstable or inactive. The second cell population, having normal or near normal pHi, was considered metabolically active with adequate values of ATP and PCr. We can therefore further analyze the bioenergetics in this cell population. The results were based upon studies of 14 ischemic dogs that were anesthetized with 2% isoflurane and ventilated. The amount of Pi associated with the acidic cell population (low pHi) was used to calculate the fraction of metabolically inactive brain tissues. This value correlated well with the ATP depletion of the total cell population. This suggests that in the acidic cell population, PCr and ATP supplies were depleted by dephosphorylation during ischemia, leading to an accumulation of acidic Pi. In addition, ATP synthesis in this population may be inhibited by the low intracellular pH. On the other hand, the bioenergetic state of the metabolically stable cell population having a nearly neutral pHi changed markedly during ischemia. The PCr/Pi dropped to 0.8 and the phosphorylation potential (PP) dropped to 10 mM-1 from 40 mM-1. With reperfusion, two distinct patterns of responses were observed. One group showed the restoration of ATP (recovery group) whereas the second group did not (non-recovery group). After 3 h of reperfusion, the ATP restored group showed complete recovery of PCr.(ABSTRACT TRUNCATED AT 250 WORDS)
Nioka
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S
Department of Biochemistry and Biophysics, University of Pennsylvania 19104.
Smith
D
D
Chance
B
B
Lockard
S
S
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D004285:Dogs; D004734:Energy Metabolism / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D010766:Phosphorylation; D015427:Reperfusion Injury / Q000378:metabolism*; D013055:Spectrophotometry, Infrared