Electrocardiographic and Ultrastructural Cardiac Effects of Phenothiazine in Rabbits

Electron microscopic study of the hearts of rabbits given short-term high dosages of chlorpromazine revealed changes similar to those found in phenothiazine-treated human subjects who died suddenly. These consisted of severe mitochondrial pleomorphism, loosening of myocardial fiber structure, and intracytoplasmic edema. Widening of Z-band spaces also occurred, as in the human hearts, suggesting incomplete cardiac contraction. A direct effect of phenothiazine drugs on mitochondrial structure and function is suggested and, if sufficiently widespread or strategically located, this effect can trigger changes in cardiac rhythm.