Calcium-channel blockers: Effects on cerebral blood flow and potential uses for acute stroke

Current research suggests that ischemia induces a massive shift of calcium from the extracellular fluid to the intracellular space. This is associated with a precipitous decrease in the concentration of adenosine triphosphate, the energy source required to drive the ion pumps of the calcium channels that maintain intracellular calcium homeostasis. The result is a further increase in free intracellular calcium, leading to calcium overload and thus to cell catabolism and cell necrosis. Treatment with calcium-channel blockers may therefore offer a new approach to arresting and, possibly, preventing destruction of cerebral tissue in stroke victims. Animal studies using nimodipine, a calcium antagonist with marked vasodilator effects, have shown that this agent prevents both spasm of the isolated rabbit basilar artery, produced either by depolarization or by receptor stimulation, and postischemic impairment of cerebral blood flow (CBF), which may be a major contributor to neuronal damage. In patients with acute ischemic stroke, intravenous nimodipine therapy caused a dose-dependent increase in hemispheric CBF. These data prompted us to conduct a prospective, single-blind, randomized trial of 60 patients to determine whether nimodipine treatment would reduce neurologic deficits in patients with acute ischemic stroke. The 29 treated patients were given standard dextran therapy supplemented with daily 120 mg doses of nimodipine, and the 31 control subjects received dextran therapy alone. Mathew scale neurologic scores indicated decreased consciousness and impaired cerebral function in both treated and control groups; however, cerebral deficits were significantly smaller in patients who received nimodipine. Adverse effects were minimal and clinically insignificant. These preliminary results suggest that calcium shifts can greatly influence the extent of cerebral damage in stroke victims and calcium antagonists may be useful in treating such patients.