Dissociation of hemodynamic and metabolic effects of propionyl-L-carnitine in ischemic pig heart

Abstract

Propionyl-L-carnitine protects ischemic myocardium in the isolated working rat heart preparation [1] and enhances recovery of myocardial function following mild myocardial ischemia in an in vivo porcine model [2]. The enhanced recovery of post-ischemic myocardium has been ascribed to a positive inotropic action of the drug [2]. Stimulation with catecholamines will also improve function of depressed post-ischemic (“stunned”) myocardium [3, 4], but this is accompanied by a shift in substrate utilization in favor of free fatty acids [4, 5]. Free fatty acid oxidation could, however, still be impaired because of a carnitine deficiency, depletion of mitochondrial pools of citric acid cycle intermediates and fatty acyl-CoA inhibition-induced adenine nucleotide translocation across the inner mitochondrial membrane. Propionyl-L-carnitine administration has the potential to relieve the deficiency of carnitine, to supply propionyl-CoA as a source of succinyl-CoA and to reduce fatty acyl- CoA accumulation (as we discussed in [6]). In this respect it is of interest that carnitine has increased the tolerance to pacing-induced myocardial ischemia in patients undergoing diagnostic cardiac catheterization [7]. Thus, propionyl-L-carnitine could, because of its metabolic actions, be useful during inotropic stimulation of post-ischemic myocardium with catecholamines.

“Post-ischemic blood flow to the myocardium perfused by the left anterior descending coronary artery was higher in the propionyl-L-carnitine-treated than in the untreated animals. It has been well established that reperfusion after a prolonged period of myocardial ischemia does not always result in a complete return of blood flow since the vasculature of the ischemic myocardium can become obstructed by extravascular compression or by intravascular obstructions (the “no-reflow”-phenomenon). It could then be argued that propionyl-L-carnitine treatment attenuated this no-reflow phenomenon.”