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September 1, 1983Journal of Cardiovascular Pharmacology

Interaction of External Calcium Concentration and Verapamil on the Effects of Doxorubicin (Adriamycin) in the Isolated Heart Preparation

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Why the study?

Does doxorubicin interact with external calcium concentration and verapamil to affect left ventricular function in isolated rabbit hearts?

Population

Isolated rabbit hearts perfused at four different concentrations of CaCl2 (2.4, 1.6, 1.2, and 0.8 mM)

Comparison

Doxorubicin (adriamycin) with or without verapamil vs Baseline function before doxorubicin…

Design

Preclinical

Authors

SRSimon W. Rabkin

Discussion

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Overview

May worsen contractility with verapamil or low calcium; hypothesis-generating in isolated hearts, clinical relevance remains open.

Key Points

  • To determine the acute effects of doxorubicin on left ventricular function relative to extracellular calcium concentrations and verapamil exposure.
  • Perfused isolated rabbit hearts with four varying concentrations of calcium chloride (0.8, 1.2, 1.6, and 2.4 mM).
  • Assessed left ventricular function and contractility metrics, including positive and negative dP/dt and developed pressure, following adriamycin and verapamil administration.
  • Adriamycin induced significant reductions in positive dP/dt and developed pressure across all tested calcium concentrations (p < 0.05), though elevating extracellular calcium in its presence significantly improved contractility (p < 0.05).
  • Verapamil caused significant calcium-dependent negative inotropic effects (p < 0.05), and adding adriamycin after verapamil resulted in a further significant decline in positive dP/dt (p < 0.05).

Structured PICO

Does doxorubicin interact with external calcium concentration and verapamil to affect left ventricular function in isolated rabbit hearts?

P
Population
Isolated rabbit hearts perfused at four different concentrations of CaCl2 (2.4, 1.6, 1.2, and 0.8 mM)
I
Intervention
Doxorubicin (adriamycin) with or without verapamil
C
Comparator
Baseline function before doxorubicin administration
O
Outcome
Left ventricular function (positive dP/dt, developed pressure, negative dP/dt)surrogate

Doxorubicin further decreases myocardial contractility in the presence of low external calcium or verapamil, suggesting a potential adverse interaction.

Cite This Study

Simon W. Rabkin (1983) studied this question.

synapsesocial.com/papers/6a7e520691d72aebec32f76dhttps://doi.org/10.1097/00005344-198309000-00022
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