Influence of chlorpromazine on lysosomal alterations during myocardial ischaemia

Ligation of the circumflex artery of anaesthetised, open-chest rabbits caused a progressive increase in nonsedimentable cathepsin D activity in severely ischaemic myocardium and an anatomical redistribution of the enzyme from lysosomes into the cytosol, along with progressive ultrastructural signs of cellular damage and necrosis. Chlorpromazine pretreatment (15 mg X kg-1 intravenously) reduced the increase in nonsedimentable cathepsin D activity slightly, but no appreciable protective effect on the anatomical redistribution of the enzyme or the development of ultrastructural signs of necrosis could be detected. It is concluded that in this experimental model of myocardial infarction, high concentrations of chlorpromazine have a mild stabilising action on lysosomes, but the drug has minimal if any effect in protecting the heart from ischaemic damage.