The effect of verapamil on cardiac sympathetic function

We have used systolic time intervals (STI) to measure inotrophy and chronotropy as indirect measures of the actions of noradrenaline, in order to ascertain whether the depletion of cardiac noradrenaline stores which has been shown to occur in laboratory rats after chronic verapamil treatment could be demonstrated in healthy volunteers. Placebo, verapamil, or atenolol were given by slow intravenous injection to 8 healthy volunteers and QS2I, LVETI, and PEP/LVET were measured. Verapamil pretreatment resulted in a positive inotropic state. Intravenous verapamil after oral pretreatment caused accentuated negative inotropic and chronotropic responses as compared with acute verapamil without pretreatment. We postulate that the observed initial inotropic effect may be in part due to an increase in the amount of noradrenaline available to the myocardium intrasynaptically, and that the accentuated negative response after intravenous or oral verapamil may result from a decrease in cardiac noradrenaline storage.