THE EFFECTS OF m‐AMSA ON RAT ISOLATED HEART

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.