Adult rat myocardial slices: A tool for studies of comparative cardiotoxicity.
The applicability of myocardial slices in comparative cardiotoxicity studies was investigated using the known cardiotoxicants allylamine (AAM) and doxorubicin (DOX). Precision-cut adult rat myocardial slices are a recently developed in vitro system. Previously, it has been demonstrated that myocardial slices are viable for up to 24 hr in organ culture. Myocardial slices exhibited a concentration- and time-dependent loss of viability in response to exposure to AAM or DOX (10(-7), 10(-6) or 10(-5)m) during 24 hr in culture, as assessed by biochemical parameters including protein synthesis, ATP content, lipid peroxidation and the loss of the cytosolic enzyme creatine kinase. Protein synthesis and ATP content were sensitive indicators of slice viability, while lipid peroxidation was affected only by 10(-5)m DOX. Myocardial slices appear to be a useful in vitro system for the study of the cardiotoxic potential of chemicals. The maintenance of normal cellular architecture makes myocardial slices uniquely attractive for these studies.
Parrish
A R
AR
Department of Pharmacology, University of Arizona, Health Sciences Center, Tucson, Arizona, USA.
Dorr
R T
RT
Gandolfi
A J
AJ
Brendel
K
K