Use of cell culture for optimisation of direct antiatherogenic therapy with verapamil.

The potential of verapamil to prevent atherogenesis induced by atherogenic serum in cell culture was investigated. Smooth muscle cells were cultured from human aortic intima and incubated with blood serum from patients with coronary artery disease. Only serum causing a significant rise in total cholesterol content in cultured cells during a 24-hour incubation period was used. The addition of verapamil to cells decreased serum-induced cholesterol accumulation. The maximum antiatherogenic effect of verapamil in vitro was recorded at 10(-5) to 10(-4) mol/L. Blood serum obtained from patients before and after oral verapamil administration was added to cultured cells. The atherogenic potential of serum obtained after verapamil administration was significantly lower than the predose value. To optimise direct antiatherogenic therapy with verapamil, the minimum dose that produced the maximum effect was established as 30 to 40mg. Using a 40mg dose, the maximum effect of oral verapamil was observed 3 hours after administration. A second 40mg dose was given 5 hours after the first dose, when the blood serum atherogenic potential was about 40% of the predose value and rising. This second dose maintained the atherogenic potential of serum at about 40%. Thus, to decrease atherogenic potential of serum and to maintain it at a low level, verapamil should be administered at a dose of 40mg 5 times daily with a 4- to 5-hour interval between doses.