The disappearance of high-energy
phosphates (HEPs) in the rat brain during global
ischemia induced by
cardiac arrest is slowed down significantly by
dihydropyridine Ca antagonists (DCAs) compared to controls. Two mechanisms might account for this effect: increased HEP production via anaerobic glycolysis or decreased HEP consumption. In order to obtain more insight into the underlying mechanisms of
ATP preservation we have studied in the rat the effect of the DCAs
isradipine,
darodipine and
nimodipine on the cerebral steady-state levels of HEPs and
lactate as well as the intracellular pH value during global
ischemia using combined 31P/1H magnetic resonance spectroscopy. We have found that the
ATP preservation in DCA-treated animals is not associated with significantly higher postischemic
lactate levels (
lactate/
N-acetylaspartate 0.97 +/- 0.08 for
isradipine at a dose of 2.5 mg/kg i.p.) or lower pH values (6.40 +/- 0.03) as compared to control rats (
lactate/
N-acetylaspartate 0.94 +/- 0.13, pH = 6.49 +/- 0.03). This is in contrast to hyperglycemic rats, in which similar preservation of
ATP levels during
ischemia was observed; however, at the expense of a larger drop in brain pH (6.22 +/- 0.09) and a concomitant increase in cerebral
lactate (
lactate/
N-acetylaspartate = 1.40 +/- 0.09). These results strongly favor reduced
ATP consumption to be the cause for the protective effect of DCAs.(ABSTRACT TRUNCATED AT 250 WORDS)