Cardiac Electrophysiologic Effects of 9‐Deoxydoxorubicin
作者:
VICTOR MOLINA‐VIAMONTE,
MARY HAMRA,
MICHAEL R. ROSEN,
期刊:
Journal of Cardiovascular Electrophysiology
(WILEY Available online 1991)
卷期:
Volume 2,
issue 5
页码: 419-430
ISSN:1045-3873
年代: 1991
DOI:10.1111/j.1540-8167.1991.tb01342.x
出版商: Blackwell Publishing Ltd
关键词: anthracycline antibiotics;cellular electropharmacology;antiarrhythmic drugs;action potentials;ventricular tachycardia
数据来源: WILEY
摘要:
Electrophysiology of 9‐Deoxydoxorubicin.Introduction: The purpose of this investigation was to use standard microelectrode techniques to study the actions of the anthracycline antibiotic, 9‐deoxydoxorubicin (9‐DOD), on cellular electrophysiologic properties of canine Purkinje fibers and on ouabain‐induced ventricular tachycardia (VT) in intact dogs.Methods and Results: 9‐DOD, 1‐5μM, suppressed delayed afterdepolarizations and prolonged repolarization and the effective refractory period in Purkinje fibers. It had no effect on maximum diastolic potential, V̇maxof phase 0, or action potential overshoot through a 10μM concentration. Although 9‐DOD did augment early afterdepolarizations (EAD) induced by cesium, it did not induce EAD. In six of eight intact dogs with ouabain‐induced VT, 9‐DOD, 0.32‐1.28 mg/m2IV, brought conversion to sinus or junctional rhythm. In its cellular and intact animal antiarrhythmic actions, 9‐DOD is about 50 times more potent than the parent compound, doxorubicin. Like doxorubicin, it is highly selective for delayed afterdepolarization‐induced rhythms, suppressing these at concentrations lower than those required to reduce the rate of automatic rhythms. Moreover, it has a greater Class III action than doxorubicin and prolongs the duration of normal and calcium‐induced (slow response) action potentials. Hence, this subtle variation on the doxorubicin molecule adds greatly to the antiarrhythmic action of the drug.Conclusions: Although useful as an investigative tool, clinical development of 9‐DOD as an antiarrhythmic is not possible because the antitumor activity of the parent compound, which results in lipid peroxidatio
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