Cardiac Hypertrophy in the Dog and Rat Induced by Oxfenicine, an Agent Which Modifies Muscle Metabolism

Abstract

Oxfenicine (S-4-hydroxyphenyl glycine) has been shown to protect the rat and dog heart from experimentally induced myocardial ischaemia probably as a result of its ability to divert myocardial metabolism from fatty acid to carbohydrate utilization with a consequent reduction in oxygen consumption. When various dose levels of oxfenicine were administered to dogs for periods of up to 1 year and rats for periods of up to 2 years, dose-related increases in cardiac weight were observed. No increases in cardiac weight were observed in the rat after only 3 months of treatment but increases were observed in the dogs after a similar treatment period. Macroscopic, light, histochemical and electron microscopic examination of the myocardium revealed that the increase in heart weight was due to uniform myocardial fibre hypertrophy involving all cardiac chambers. Individual muscle fibres were increased in size but there was no clear disproportion of mitochondria and myofibrils. Although intracellular lipid was increased, vacuolated lysosomal structures were only occasionally observed. No histochemical differences in lysosomal enzyme activity were observed between the treated and the control rats. The structural changes were fully compatible with myocardial hypertrophy due to the decreased energy forming capacity of heart muscle resulting from inhibition of fatty acid oxidation by oxfenicine.