Effects of L-propionylcarnitine on ischemia-induced myocardial dysfunction in men with angina pectoris.
To identify the effect of L-propionylcarnitine (LPC) on ischemia, 31 fasting, untreated male patients with left coronary artery disease were studied during 2 identical pacing stress tests 45 minutes before (atrial pacing test I [APST I]) and 15 minutes after (APST II) administration of 15 mg/kg of LPC or placebo. Hemodynamic, metabolic, and nuclear angiographic variables were studied before, during, and for 10 minutes after pacing. After LPC administration, arterial total carnitine levels increased from 47 +/- 1.7 mumol/liter (control) to 730 +/- 30 mumol/liter. Hemodynamic and metabolic variables were comparable in LPC and placebo during APSI I, and reproducible in placebo during both tests. Although LPC did not affect myocardial oxygen demand and supply, it diminished myocardial ischemia, indicated by a significant 12% and 50% reduction in ST-segment depression and left ventricular end-diastolic pressure, respectively, during APST II. Moreover, during APST II, left ventricular ejection fraction increased by 18% (p < 0.05 vs APST I). Furthermore, LPC improved recovery of myocardial function after pacing, with a reduction in the time to peak filling and a 21% increase in both peak ejection and filling rates 10 minutes after pacing (all p < 0.05). Thus, LPC prevents ischemia-induced ventricular dysfunction, not by affecting the myocardial oxygen supply-demand ratio but as a result of its intrinsic metabolic actions, increasing pyruvate dehydrogenase activity and flux through the citric acid cycle. Because it is well tolerated, it may be a valuable alternative or addition to available antiischemic therapy.
Sticares Cardiovascular Research Foundation, Zuiderziekenhuis, Rotterdam, The Netherlands.
G L
GL
Bartels
W J
WJ
Remme
M
M
Pillay
D H
DH
Schönfeld
D A
DA
Kruijssen
D000368:Aged; D000787:Angina Pectoris / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000097:blood / Q000627:therapeutic use*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D003327:Coronary Disease / Q000150:complications / Q000473:pathology; D004562:Electrocardiography; D005080:Exercise Test; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000097:blood; D007773:Lactates / Q000097:blood; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D010919:Placebos; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology; D017725:Ventricular Pressure / Q000187:drug effects / Q000502:physiology
D002316:Cardiotonic Agents; D007042:Hypoxanthines; D007773:Lactates; D010919:Placebos; C003223:propionylcarnitine; D019271:Hypoxanthine; D002331:Carnitine