EFFECTS OF PROPIONYL-L-CARNITINE IN CHRONICALLY HYPOPERFUSED (HIBERNATING) MYOCARDIUM

The purpose of this report was to test the effects of systemic treatment with propionyl-L-carnitine in a new model of chronically hypoperfused ("hibernating") myocardium. Adolescent swine were instrumented to undergo a period of mild partial coronary constriction for 1 week (50% reduction of the maximum phasic flow velocity in the anterior descending coronary artery). This reduced regional mechanical function by 56%. The system satisfied criteria defining "hibernating" myocardium, in that the chronic hypoperfusion did not produce massive tissue necrosis and that the reduction in regional contraction remained responsive to inotropic stimulation. Treatment with 50 mg/kg propionyl-L-carnitine by mouth twice daily for 1 week significantly (p < 0.0005) increased concentrations of free and total carnitine in the myocardial tissue by 39% and 31%, respectively. Treatment with propionyl-L-carnitine did not alter regional systolic shortening in either hibernation or reperfusion for 2 hours, but enhanced one estimate of contractility reserve based on the rate of left ventricular emptying with occlusion of the inferior vena cava. Propionyl-L-carnitine did not reverse the observed impairments in mitochondrial respiration (diminutions in state 3 respiration and the respiratory control ratio), but limited the number of lesions seen on histological examination. Six out of eight placebo hearts showed one or more changes of ischemia, infarction or reperfusion injury, while the same was true in only two out of eight hearts treated with propionyl-L-carnitine (p < 0.003). Carnitine and various analogues have been proposed to benefit ischemic myocardium. The present data suggest that this general sparing effect may also occur with the propionyl derivative in chronically underperfused myocardium.