Temperature dependence of calcium antagonist action

Calcium-tolerant ventricular myocytes from adult rats were electrically stimulated. The maximal contraction frequency (fm) was determined at different temperatures. In drug-free Tyrode solution, fm follows the Arrhenius equation from 7 to 39.5 degrees C. However, all investigated calcium antagonist drugs (verapamil, nifedipine, diltiazem, fendiline) introduce a discontinuity between 27 and 30 degrees C into the Arrhenius plots of fm. Above this transition temperature calcium antagonists lower fm more pronouncedly than below. Below, 10- or 100 fold higher concentrations are needed for the same relative effect as at 37 degrees C. It is argued that these findings might be important in cardiac surgery when calcium antagonists are used for cardioplegia at deep hypothermia.