The effect of a calcium antagonist (D600) on isoprenaline-induced myocardial necrosis in the rat.

The effect of inhibiting isoprenaline-induced intracellular calcium accumulation on the degree of damage produced in the rat myocardium by this amine has been investigated by simultaneously dosing rats with the calcium antagonistic drug D600. The degree of myocardial necrosis produced in animals given isoprenaline alone and those given D600 was measured by the use of a standard point counting method to show absence of formazan from dead muscle fibres in sections treated to demonstrate succinic dehydrogenase. The use of the calcium antagonistic drug D600 considerably reduced the degree of myocardial damage produced by a standard dose of isoprenaline bitartrate. This was associated with a decrease in the isoprenaline-induced cellular calcium uptake. The results are discussed in relation to the possible protection conferred by lowering of the calcium influx at the cell membrane and the maintenance of the cells' high-energy phosphates at a level which permits "normal" cell function.