A cell culture assay for the detection of cardiotoxicity.

An important step in minimizing the number of animal experiments in medical research is the study of in vitro model systems. We propose the use of "shock protein" formation, which is a cellular response to cell-damaging stress as an assay to monitor cardiotoxicity. Isolated and cultured cardiac myocytes were prepared by a trypsin digestion method from 18-day-old fetal mice. These cells respond to typical substances inducing "shock protein" formation in other cellular systems as well as to known cardiotoxins with the de novo synthesis of "shock proteins." Pharmaceuticals relevant in transplant medicine were tested for possible cardiotoxic effects: Cyclosporine A evokes "shock protein" formation at subtherapeutic concentrations. Azathioprine and methyl-prednisolone exert the same effect but at concentration ranges highly above the therapeutic level. The ability to induce "shock protein" synthesis obviously seems to be restricted to toxic drugs. The data presented demonstrate that the proposed in vitro model system for cardiotoxicity is animal saving and sensitive.