THE EFFECTS OF m‐AMSA ON RAT ISOLATED HEART

SUMMARY 1. m-AMSA (4′[9-acridinylamino]methansulphon-m-anisidide) is a new cytoxic agent now under clinical trial. 2. We used the rat isolated perfused heart model in order to investigate the cardiac effects of m-AMSA. 3. The results of the dose-response study indicate that m-AMSA has an acute moderate negative inotropic effect. The 90% effect (25% decrease in developed force compared to the control) was observed at drug concentration of 1.5 μg/ml. The refractory period (as measured by stimuli of twice diastolic threshold intensity) increased progressively as the drug concentration was increased (up to 2.5 μg/ml). 4. Measurements of the strength-duration and strength-interval relationship showed that m-AMSA induced a significant reduction (P < 0.005) in excitability and prolongation of refactoriness. 5. We suggest that m-AMSA has a membranal cardiotoxic effect in addition to its known intracellular cytotoxic effect.