Pretreatment with chlorpromazine prevents phospholipid degradation and creatine kinase depletion in isoproterenol-induced myocardial damage in rats.

We investigated the effect of chlorpromazine on myocardial phospholipid content and composition and on myocardial creatine kinase (CK) activity in rats with isoproterenol-induced myocardial damage. A single subcutaneous injection of isoproterenol (40 mg/kg) increased heart weight but decreased myocardial phospholipid content and CK activity 24 h after administration. Total phospholipid content was significantly correlated with myocardial CK activity. The decrease of total phospholipid content was accompanied by an increase of the lysophosphatidylcholine (LPC)/phosphatidylcholine (PC) ratio, indicating that conversion from PC to LPC had occurred. Intraperitoneal injection of chlorpromazine (30 mg/kg) prior to isoproterenol injection inhibited the decrease in total phospholipid content and CK activity and the increase in the LPC/PC ratio, but did not affect the increase in heart weight. Pretreatment with propranolol (20 mg/kg) reversed the effects of isoproterenol. On the other hand, dexamethasone (12 mg/kg) and verapamil (50 mg/kg) had no significant effects on the above parameters of myocardial damage. These results suggest that prevention of myocardial phospholipid disruption inhibits enzyme depletion from the myocardium and that chlorpromazine helps to prevent isoproterenol-induced myocardial damage by improving phospholipid metabolism.