Influence of flunarizine on postischemic flow and energy metabolism in the isolated rat brain.

Isolated perfused rat brains were subjected to complete ischemia. Reperfusion was started 10 min after the negative DC-shift. In control brains, recovery of flow was retarded and, after 10 min of reperfusion, a delayed hypoperfusion developed. In flunarizine-treated brains, recovery of flow was considerably steeper, complete and without reduction during the further course of reperfusion. Additionally, restoration of energy metabolism and mitochondrial function was significantly improved. The effect on the energetic state of the brains was at least partly independent of the improvement of flow. This could be concluded from experiments in which reperfusion was commenced simultaneously with DC-negativation. In these experiments, flow recovery was prompt and complete in control as well as in treated brains. Nevertheless, treated brains exhibited after reperfusion significantly better ratios of ATP to ADP and normalized levels of lactate and succinate.