Protective effects of flunarizine on hemorrhagic shock in rats

Intravenous injections of flunarizine 0.25, 0.5, or 1.0 mg.kg-1 10 min before hemorrhage increased the maximal bleeding volume from 4.3 +/- 1.1 to 5.5 +/- 1.1 ml. As the dose of flunarizine increased, the survival time in rats subjected to hemorrhage was prolonged in a dose-dependent manner. Five hours after the reinfusion, flunarizine 1 mg.kg-1 markedly improved the survival rate to 70% compared with nil in the shock group. Flunarizine reduced the increase of lactate in blood, ameliorated the depletion of ATP stores in tissues, and prevented the calcium accumulation in heart and liver. The results suggest that flunarizine may produce a protective effect on hemorrhagic shock, probably related to the decrease of calcium accumulation in the ischemic tissues.