The Effect Of Adriamycin On The Isometric Contraction Of Guinea-Pig Papillary Muscle. Muscle mechanics and Electrophysiology

Abstract

Previous studies pointed out that severe cardiotoxic side effects restrict the use of Adriamycin (A) as an effective cancer therapeutic agent. In order to study acute and chronic A-effects on muscle mechenics and electrophysiological properties, experiments were done in isolated papillary muscles from guinea-pig under conditions of isometric contraction. Action potential was measured by use of glass micro-electrodes. In 28 muscles of not pretreated animals maximum isometric tension development (Tmax) was reduced by 15,8±7,5% following an increasing A-concentration (2–80/μg/ml). Maximum rate of tension development (dT/dtmax) decreased by 14.7μ5.9%. Maximally effective concentration: 8–10/μg/ml. Electrophysiological properties such as resting potential, action potential, overshoot, upstroke velocity and duration of action pot. did not change. After pretreatment with A for 1–4 courses (course: 3 days 1mg/kg A; 4 days interval) maximum isometric tension development/cross sectional area and further acute A-effect were reduced variably, when compared to untreated animals. However, the cardiotoxic effect of A-pretreatment became more evident and reproducable after addition of epinephrine (12/μg/ml). Whereas Tmax of muscles from untreated animals increased by about 100% there was a diminuation of response in muscles of pretreated animals. This diminuation could be correlated with duration and dose of A-pretreatment. In summary and conclusion: 1.Both, acute and chron. A-effects can be observed. 2.Musclemech. changes are not due to changes in electrical membrane properties or to change in exciting-contraction coupling. 3.Cardiotoxic effect (clinically often sudden, irreversible congestive heart failure) may be detected most sensitive by (clinical) use of a stimulatory test.