Acute effect of calcium channel blockers on adriamycin exposed isolated adult cardiocytes.
When tested with isolated, calcium-resistant resting rat cardiocytes in an in vitro assay system, adriamycin exerted a dose-dependent cytotoxic effect which could easily be assessed by the ATP depletion of the heart cells and the loss of vitality as monitored by morphological changes (blebbing, spherical contraction). Apart from extremely high non pharmacological concentrations of verapamil and diltiazem, both calcium antagonists left the cardiocytes intact and without loss of internal ATP when given alone to the medium. Coincubation of adriamycin and verapamil or diltiazem did not increase adriamycin toxicity to the cardiocytes; instead a remarkable ATP preservation by verapamil could be demonstrated when both drugs (adriamycin and verapamil) were incubated simultaneously with the heart cells. This acute protective effect was limited in time and could no longer be detected after 9 hours. Diltiazem in coincubation experiments exerted neither a toxic nor an acute protective effect on adriamycin-exposed heart cells.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000633:toxicity; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology / Q000633:toxicity*; D004359:Drug Therapy, Combination; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D051381:Rats; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004317:Doxorubicin; D000255:Adenosine Triphosphate; D014700:Verapamil; D004110:Diltiazem