Acute negative inotropic effect of adriamycin (doxorubicin)

The muscle mechanical and haemodynamic effects of adriamycin were investigated in guinea pigs and rats by use of isolated myocardium (isometric contractions of papillary muscles of guinea pigs and rats) and in situ preparations (haemodynamic parameters in thoracotomized rats). 1. Adriamycin (10-6 to 10-3 M) produced a concentration-dependent negative inotropic effect in papillary muscles of 21 guinea pigs (decrease of T max and dT/dt max to 80% of control) and in papillary muscles of 15 rats (decrease of T max and dT/dt max to 25% of control for maximally effective concentrations). 2. The haemodynamic parameters left ventricular pressure (LVP), dLVP/dt max, arterial pressure and cardiac output of thoracotomized rats (N = 12) decreased dose-dependently following i.v. injections of adriamycin at doses of 2-30 mg/kg until a lethal haemodynamic shock occurred. 3. "Low-dose-effects" were reversible within min, whereas "high-dose-effects" were not up to an observation period of 1 h. 4. In the haemodynamic experiments, the ionized serum calcium fell excessively after adriamycin (from 2.1 mEq/l for controls to 0.5 mEq/l after doses of 25 mg/kg adriamycin). 5. An antagonistic interaction was seen between the cardio-depressant effect of adriamycin and the positive inotropic effect of calcium and vice versa. 6. It is concluded that the acute muscle mechanical and haemodynamic effects of adriamycin result from an interaction between adriamycin and calcium.