Effects of repeated ischemia on cerebral blood flow and brain energy metabolism

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Abstract
To determine if cerebral blood flow (CBF) and cerebral metabolic alterations during partial ischemia are affected by a prior interval of ischemia, 13 neonatal piglets were studied during two successive protocols (termed A and B), each consisting of an interval before, during and after partial ischemia induced by hypotension. Piglets were studied with either microspheres (n = 6) to measure CBF and calculate cerebral uptake of O2 and glucose or 31P nuclear magnetic resonance spectroscopy (n = 6) to measure intracellular pH (pHi) and cerebral phosphorylated metabolites. One piglet was used to determine time effects. Control values of all variables were similar during protocol A and B. In each protocol hypotension was associated with similar reductions in CBF and cerebral O2 uptake but cerebral glucose uptake differed (0.10 ± 0.05 vs 0.05 ± 0.02 mmol · min−1 · 100 g−1 during hypotension of A and B, respectively, p < 0.05). During hypotension of protocol A and B similar changes in phosphorylated metabolites and pHi occurred and were characterized by a reduction in pHi, phosphocreatine and adenosine triphosphate and an increase in inorganic phosphate. Changes in phosphate metabolites and pHi were reversible within 25 min following hypotension in both protocols. Thus, changes in CBF, cerebral O2 uptake, pHi and cerebral energy metabolism are similar during repeated episodes of partial ischemia. However, differences in cerebral glucose uptake in protocol A and B raise the possibility that the balance between energy production and utilization is altered, or alternative substrates are metabolized or enzymatic activity in the glycolytic pathway is changed.