Interaction of external calcium concentration and verapamil on the effects of doxorubicin (adriamycin) in the isolated heart preparation.
The purpose of this investigation was to determine the acute effects of adriamycin (doxorubicin) on left ventricular function in the isolated heart preparation with regard to its relationship to external calcium concentration, [Ca]0, and the calcium entry-blocking drug verapamil. Isolated rabbit hearts were perfused at four different concentrations of CaCl2 (2.4, 1.6, 1.2, and 0.8 mM). Adriamycin was associated with significant (p less than 0.05) reductions in positive dP/dt and developed pressure across all calcium concentrations (analysis of covariance). The effect of adriamycin on left ventricular function was not significantly related to [Ca]0 but rather was similar at each level of [Ca]0. Increasing levels of [Ca]0 in the presence of adriamycin significantly (p less than 0.05) increased contractility. Negative dP/dt was reduced after adriamycin but was secondary to the decrease in positive dP/dt because there were no significant differences in the relationship between positive and negative dP/dt before and after adriamycin. Verapamil produced negative inotropic effects that were significantly (p less than 0.05) related to [Ca]0. The addition of adriamycin to hearts that had previously received verapamil resulted in a further significant (p less than 0.05) decrease in positive dP/dt. Thus, low [Ca]0 and the calcium entry-blocking agent verapamil reduce myocardial contractility. Contractility is further decreased after adriamycin, suggesting a potential adverse interaction of these agents.
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006321:Heart / Q000502:physiology*; D006334:Heart Function Tests; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D011817:Rabbits; D014700:Verapamil / Q000494:pharmacology*
D004317:Doxorubicin; D014700:Verapamil; D002118:Calcium