The effects of propionylcarnitine taurine on cardiac performance in aerobic and ischemic myocardium.
Carnitine, certain of its derivatives, and the amino acid metabolite, taurine, when administered independently in prior studies have been shown to improve cardiac mechanic and/or metabolism. The purpose of these studies is to test a new compound, propionylcarnitine taurine (PCT), which potentially combines these actions, in a therapeutic trial to preserve function in a setting of myocardial ischemia. In the main protocol, PCT was administered (0.71 mg/kg/min I.V.) to eight extracorporeally perfused, intact, working swine hearts over a 70 min perfusion trial and compared with seven similarly prepared placebo hearts. Left anterior descending (LAD) flows were held at aerobic levels (6.3 +/- 0.3 ml/min/g dry) for 40 min and then reduced acutely by 50% for 30 min. Serum fatty acids (FA) in both groups were augmented to 1.27 +/- 0.5 mumol/ml. Contractility (measured regionally from shortening rates of ultrasonic crystals placed in the LAD circulation); myocardial oxygen consumption (MVO2); and FA oxidation (measured from 14CO2 production rates from labeled palmitate infused into the LAD perfusate) were obtained serially throughout the perfusion trials. Regional contractility was significantly increased in PCT-treated hearts as compared with placebo hearts both during normal and ischemic flows. Treatment appeared to deplete free carnitine stores in both aerobic and ischemic myocardium but failed to modify acyl CoA levels. In seven additional animals PCT was shown to independently stimulate fatty acid oxidation (about 39 delta % increase) at aerobic flows. Lastly in nine separate animals (4 placebo; 5 treatment) prepared and studied identically to those of the main protocol, taurine alone (0.2 mg/kg/min infused IV for 70 min) was without influence in reproducing mechanical benefits. Thus, PCT favorably enhances regional contractility in conditions of myocardial ischemia, presumably by the positive inotropic effects of the propionylcarnitine constituent of the compound.
Molaparast-Saless
F
F
Section of Cardiology, University of Wisconsin, Madison 53792.
Nellis
S H
SH
Liedkte
A J
AJ
D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003327:Coronary Disease / Q000503:physiopathology; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D010100:Oxygen / Q000502:physiology*; D010477:Perfusion; D013552:Swine; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology*
C003223:propionylcarnitine; D013654:Taurine; C052221:ST 520; D002331:Carnitine; D010100:Oxygen