THE EFFECT OF NIMODIPINE ON HIGH-ENERGY PHOSPHATES AND INTRACELLULAR PH DURING CEREBRAL-ISCHEMIA

Experimental and clinical studies suggest that the calcium channel blo cker nimodipine may reduce cerebral ischemic injury. Using rapid acqui sition phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscop y, we examined the effect of nimodipine on cerebral energy metabolism during severe ischemia in gerbils. High-energy phosphates and intracel lular pH were characterized at baseline and at 2-min intervals followi ng bilateral common carotid artery (CCA) ligation. Serial forebrain sp ectroscopy was continued until phosphocreatine (PCr) and adenosine tri phosphate (ATP) resonances disappeared. Controls (n = 10) were compare d to gerbils receiving intraperitoneal nimodipine 30 min prior to caro tid ligation, at the following doses: 0.5 mg/kg (n = 8), 1.0 mg/kg (n = 10), 2.0 mg/kg (n = 8), or 4.0 mg/kg (n = 4). In the control group, PCr and ATP peaks were undetectable after a mean of 5.4 +/- 0.47 min f ollowing CCA ligation. Compared with controls, the mean time for deple tion of high-energy phosphates following carotid ligation was prolonge d at nimodipine doses of 0.5 mg/kg and 1.0 mg/kg, but the differences did not reach statistical significance. In the 2.0 mg/kg group, howeve r, ATP was preserved until 9.8 +/- 1.0 min following the onset of isch emia, significantly longer than the control group (p = 0.005, Mann-Whi tney test). Nimodipine had no effect on the time course or severity of intracellular acidosis. In this model of severe ischemia, relatively high doses of nimodipine slowed the depletion of high-energy phosphate s without altering intracellular acidosis. This suggests that nimodipi ne may provide cerebral protection by directly altering ischemic cellu lar metabolism.