THE EFFECTS OF m-AMSA ON RAT ISOLATED HEART |
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Authors: | M S Merkin E Shinar A Shefer MS Gotsman Y Hasin |
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Institution: | Department of Cardiology, Hadassah University Hospital, Jerusalem, Israel;*Department of Hematology, Hadassah University Hospital, Jerusalem, Israel |
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Abstract: | m-AMSA (4'9-acridinylamino]methansulphon-m-anisidide) is a new cytoxic agent now under clinical trial. We used the rat isolated perfused heart model in order to investigate the cardiac effects of m-AMSA. 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 micrograms/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 micrograms/ml). Measurements of the strength-duration and strength-interval relationship showed that m-AMSA induced a significant reduction (P less than 0.005) in excitability and prolongation of refactoriness. We suggest that m-AMSA has a membranal cardiotoxic effect in addition to its known intracellular cytotoxic effect. |
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Keywords: | cardiac excitability cardiotoxicity m-AMSA myocardial developed force |
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