Effects of chloroquine and didesethylchloroquine on rabbit myocardium and mitochondria

The effects of chloroquine and didesethylchloroquine on the rabbit isolated perfused heart and on calcium binding and accumulating ability of the heart mitochondria were investigated. The drugs produced negative chronotropy, negative inotropy and a decrease in coronary flow rate in the isolated perfused myocardium. Both chloroquine and didesethylchloroquine significantly decreased mitochondrial calcium binding and accumulation. These results suggest that the cardiodepressant actions of chloroquine could be due in part to alterations in the calcium accumulating abilities of the mitochondrial membranes, and that didesethylchloroquine, among other metabolites, does contribute significantly to the total observed effect of chloroquine on the cardiovascular system.