An approach to the problem of metabolic heterogeneity in brain: ischemia and reflow after ischemia.

We have proposed that tissue metabolic failure during hypoxia or ischemia is related to the microheterogeneous distribution of tissue oxygen and not to failure of the creatine kinase equilibrium. This theory is based on the concept that sharp oxygen gradients exist in rapidly metabolizing tissue and that shifts in these gradients can place specific cells at risk for metabolic death while relatively adjacent cells escape unharmed; cells that are unharmed meet the steady-state requirements (V less than Vmax), those at risk do not (V greater than Vmax). Though it would seem that confirmation of such a hypothesis would require metabolic delineation at a high resolution, we have shown how 31P MRS provides information supporting this hypothesis. This possible use of MR spectroscopy to define microheterogeneous events suggests further clinical possibilities for this instrument in defining the rate of cell loss and the response to therapeutic interventions.