Propionyl-L-carnitine improves hemodynamics and metabolic markers of cardiac perfusion during coronary surgery in diabetic patients.
Diabetic hearts are particularly vulnerable to ischemia-reperfusion injury during cardiac surgery. Application of carnitine derivatives could be beneficial not only because of metabolic effects but also by protecting vasculature. This study aimed to evaluate hemodynamic changes associated with propionyl-L-carnitine and L-carnitine administration and its correlation with biochemical markers of cardiac vascular function.


METHODS
Sixty-eight diabetic patients undergoing cardiopulmonary bypass coronary operation were given intravenously 20 mg/kg b.w. L-carnitine (LC), 24 mg/kg b.w. propionyl-L-carnitine (PC), or placebo (Cont). Endothelin and nucleotide metabolites were determined intraoperatively in arterial and coronary sinus blood and heart biopsies.


RESULTS
Cardiac index at 6 and 12 h after cardiopulmonary bypass was significantly higher in PC (3.30 +/- 0.12 and 3.47 +/- 0.15 L/min/m2) as compared to Cont (2.92 +/- 0.13 and 2.91 +/- 0.16 L/min/m2; P = 0.04 and P = 0.01, respectively). Mean pulmonary artery pressure was lower in PC at 6 (20.8 +/- 0.91 mmHg) and 12 h (20.7 +/- 0.81 mmHg) in comparison to Cont (23.5 +/- 0.75 and 23.4 +/- 0.75 mmHg; P = 0.03 and P = 0.02, respectively). Trans-cardiac endothelin difference on reperfusion was higher in Cont (0.33 +/- 0.26 pmol/L) than in LC (-0.61 +/- 0.24 pmol/L, P = 0.012) and tended to be higher than in PC (-0.29 +/- 0.17 pmol/L, P = 0.056). Trans-cardiac hypoxanthine difference after 10 min reperfusion was significantly higher in Cont (6.22 +/- 1.08 micromol/L) in comparison to LC (3.17 +/- 0.66 micromol/L, P = 0.025) and PC (2.36 +/- 0.73 micromol/L, P = 0.006). Myocardial hypoxanthine concentration was lowest in PC.


CONCLUSIONS
Significant improvement of hemodynamics following propionyl-L-carnitine administration in diabetic patients undergoing on-bypass coronary surgery was accompanied by reduced trans-cardiac endothelin difference and rapid hypoxanthine washout during reperfusion suggesting improvement of metabolism or vascular function.
Lango
Romuald
R
Department of Anesthesiology and Intensive Care, Medical University of Gdańsk, Debinki, 7 80-211, Poland. rlango@amg.gda.pl
Smoleński
Ryszard T
RT
Rogowski
Jan
J
Siebert
Janusz
J
Wujtewicz
Maria
M
Słomińska
Ewa M
EM
Lysiak-Szydłowska
Wiesława
W
Yacoub
Magdi H
MH
D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D002316:Cardiotonic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019271:Hypoxanthine / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism
D002316:Cardiotonic Agents; C003223:propionylcarnitine; D019271:Hypoxanthine; D019344:Lactic Acid; D002331:Carnitine