Calcium channel blockers in cerebral ischaemia

Ischaemic stroke usually results from the obstruction of a major cerebral vessel which leads to a decrease in cerebral blood flow, and a subsequent reduction in ATP. This energy loss leads to impaired cellular function due to reduced ATP-dependent processes and a disruption in ionic gradients across membranes. Under these conditions, there is a significant efflux of K+ from cells producing cellular depolarisation and the movement of extracellular calcium into cells through calcium channels. It is this increase in intracellular calcium that leads to the 'calcium toxicity' that has been associated with cerebral ischaemia. Increased intracellular calcium triggers the break-down of phospholipids, proteins and nucleic acids. This is activated by calcium-dependent phospholipases, proteases and endonucleases, and contributes to structural and functional damage of the cell membrane, which compromises cell function and facilitates cell death. Calcium channel blockers are used routinely to treat cardiovascular disease and hypertension. Although some experimental studies over the last decade suggest efficacy/benefit in the treatment of experimental ischaemic stroke, clinical data do not bear this out. This article discusses the role of voltage-operated calcium channel blockers in stroke, and reviews much of the available experimental and clinical data.