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Propionyl-L-Carnitine Improves Hemodynamics and Metabolic Markers of Cardiac Perfusion during Cardiopulmonary Bypass Coronary Surgery in Diabetic Patients

December 21, 2005

By Sahar Bedrood B.S. and Asher Kimchi M.D.

Gdansk, Poland - Unfavorable metabolic changes and impaired endothelial function in diabetic patients make them more susceptible to post-operative complications in cardiopulmonary bypass coronary surgery (CPB). It has been shown that carnitine administration in such patients can improve cardiac metabolism and function in ischemic patients. Suggested mechanisms include an increase in glucose metabolism and reduction of toxic effects of long-chain acyl-Co-A. Romauld Lango et al from the Medical University Gdansk, Poland evaluated hemodynamic changes associated with pre-operative propionyl-L carnitine and L-carnitine administration and its association with biochemical markers of cardiovascular function. Their study, published in the December 2005 issue of Cardiovascular Drugs and Therapy indicates a significant improvement of hemodynamics following propionyl-L carnitine administration in diabetic patients undergoing coronary-artery bypass grafting (CABG).

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.

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 control (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 control (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 control (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 control (6.22 1.08 μmol/L) in comparison to LC (3.17 0.66 μmol/L, P = 0.025) and PC (2.36 0.73 μmol/L, P = 0.006). Myocardial hypoxanthine concentration was lowest in PC.

This study demonstrates that propionyl-L-carnitine administration before CABG significantly improved post-operative recovery in early diabetic patients. The study noted improvements in cardiac index, reduction in pulmonary pressure, reduction in trans-cardiac endothelin concentration and accelerated myocardial hypoxanthine, a marker for disturbed myocardial metabolism induced by ischemia, washout. L-carnitine did not produce significant improvements in cardiovascular metabolism, thereby indicating that a specific formulation of carnitine is an important factor for future therapy.

Co-authors: Romuald Lango, Ryszard T. Smoleński, Jan Rogowski, Janusz Siebert, Maria Wujtewicz, Ewa M. Słomińska, Wiesława Łysiak-Szydłowska and Magdi H. Yacoub

 


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