The Myocardial metabolic and haemodynamic effects of perhexiline in in vivo and in vitro models / Steven Anthony Unger.

Abstract

Perhexiline is an effective anti-anginal agent without clinically significant haemodynamic effects, which is postulated to have a primary 'metabolic' mechanism of action. Recent in vitro work in isolated cardiac mitochondria suggested that inhibition of the key enzyme in the regulation of fatty acid catabolism, carnitine palmitoyltransferase (CPT-1), may play a key role in the action of perhexiline. The experiments described in this thesis are primarily aimed at investigating the postulated metabolic effects of perhexiline in the heart, and correlating these to changes in haemodynamics. Secondary aims are the assessment of the time-dependence of such changes, and the investigation of haemodynamic changes induced by parenteral perhexiline in a conscious animal model.