Cardiovascular Drugs and Therapy 19 267–275 2005 C  2005 Springer Science + Business Media, Inc. Manufactured in The Netherlands. DOI: 10.1007/s10557-005-3349-8 CLINICAL PHARMACOLOGY AND DRUG STUDIES Propionyl-L-Carnitine Improves Hemodynamics and Metabolic Markers of Cardiac Perfusion during Coronary Surgery in Diabetic Patients Romuald Lango 1 , Ryszard T. Smole ´ nski 2,3 , Jan Rogowski 4 , Janusz Siebert 5 , Maria Wujtewicz 1 , Ewa M. Slomi ´ nska 3 , Wieslawa Lysiak-Szydlowska 6 , and Magdi H. Yacoub 2 1 Department of Anesthesiology and Intensive Care, Medical University of Gda ´ nsk, Poland; 2 Heart Science Centre, Imperial College at Harefield Hospital, UK; 3 Department of Biochemistry, Medical University of Gda ´ nsk, Poland; 4 Department of Cardiac Surgery, Medical University of Gda ´ nsk, Poland; 5 Department of Family Medicine, Medical University of Gda ´ nsk, Poland; 6 Department of Clinical Nutrition, Medical University of Gda ´ nsk, Poland Published online: 20 September 2005 Summary. Diabetic hearts are particularly vulnerable to ischemia-reperfusion injury during cardiac surgery. Appli- cation of carnitine derivatives could be beneficial not only because of metabolic effects but also by protecting vascu- lature. This study aimed to evaluate hemodynamic changes associated with propionyl-L-carnitine and L-carnitine ad- ministration and its correlation with biochemical markers of cardiac vascular function. Methods: Sixty-eight diabetic patients undergoing car- diopulmonary bypass coronary operation were given intra- venously 20 mg/kg b.w. L-carnitine (LC), 24 mg/kg b.w. propionyl-L-carnitine (PC), or placebo (Cont). Endothe- lin and nucleotide metabolites were determined intraop- eratively in arterial and coronary sinus blood and heart biopsies. Results: Cardiac index at 6 and 12 h after cardiopul- monary bypass was significantly higher in PC (3.30 ± 0.12 and 3.47 ± 0.15 L/min/m 2 ) as compared to Cont (2.92 ± 0.13 and 2.91 ± 0.16 L/min/m 2 ; P = 0.04 and P = 0.01, respec- tively). 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 endothe- lin 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 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). Myocar- dial 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 ac- companied by reduced trans-cardiac endothelin difference and rapid hypoxanthine washout during reperfusion sug- gesting improvement of metabolism or vascular function. Key Words. L-carnitine, propionyl-L-carnitine, coronary surgery, diabetes mellitus, endothelin, hemodynamics, hypoxanthine, reperfusion Introduction Cardiopulmonary bypass (CPB) coronary surgery per- formed in diabetic patients with decreased left ventri- cle ejection fraction is associated with increased risk for postoperative complications [1]. This is a conse- quence of unfavorable metabolic changes and impaired endothelial function that develop in diabetic hearts. Relative carnitine deficiency has been highlighted as major factor that contributes to detrimental effects [2]. Exogenous carnitine derivatives have been shown to improve cardiac metabolism and function in ischemic heart disease and other clinical conditions associated with myocardial ischemia [3,4], but the benefit was par- ticularly significant in experimental diabetes [5]. The mechanisms of carnitine action include an increase in glucose metabolism and reduction of toxic effects of long-chain acyl-CoA that accumulates under ischemic conditions. Other effects include protection of plasma membranes [6]. Some carnitine derivatives such as propionyl-L-carnitine has additional protective effects during ischemia-reperfusion as it can be metabolized to the succinate, a substrate of citric acid cycle [7]. Recent studies indicated that in addition to well established Address for correspondence: Romuald Lango, MD, PhD, De- partment of Anesthesiology and Intensive Care, Medical Univer- sity of Gda ´ nsk, Debinki 7, 80-211 Gdansk, Poland. Tel.: +48 58 3492482; Fax: +48 58 3492471; E-mail: rlango@amg.gda.pl 267