Rescue of amitriptyline-intoxicated hearts with nanosized vesicles

OBJECTIVE: Amitriptyline, one of the most prescribed antidepressants, is reported to claim a large number of human lives due to drug overdose related cardiac arrest. Although amitriptyline poisoning has long been recognized as a frequent and serious fatality in the medical field, few efforts have been made to devise methods for treating its toxicity. To address this issue, phospholipid-based nanosized vesicles (spherulites) were employed to reverse the cardiotoxicity induced by amitriptyline in an isolated heart perfusion model. METHODS: The ability of spherulites to efficiently take up amitriptyline was first established in vitro in protein free and albumin-containing buffers. Vesicles bearing an internal pH of 3.0 or 7.4 were then infused into amitriptyline pre-intoxicated isolated rat hearts, and changes in coronary perfusion pressure (CPP), the first derivative of left ventricular pressure (dP/dt max) and heart rate were monitored. Control hearts received no vesicles. RESULTS: Based on the recoveries in CPP observed, the efficacies of the formulations were ranked as follows: control=pH 7.4-spherulites<pH 3.0-spherulites; whereas the ranking for the recoveries in heart rate was: control<pH 7.4-spherulites