Lango Romuald, Smoleński Ryszard T, Rogowski Jan, Siebert Janusz, Wujtewicz Maria, Słomińska Ewa M, Lysiak-Szydłowska Wiesława, Yacoub Magdi H
Department of Anesthesiology and Intensive Care, Medical University of Gdańsk, Debinki, 7 80-211, Poland.
Cardiovasc Drugs Ther. 2005 Aug;19(4):267-75. doi: 10.1007/s10557-005-3349-8.
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.
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 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.
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.
糖尿病患者的心脏在心脏手术期间特别容易受到缺血再灌注损伤。应用肉碱衍生物可能有益，这不仅是因为其代谢作用，还因为它对血管系统有保护作用。本研究旨在评估丙酰-L-肉碱和L-肉碱给药相关的血流动力学变化及其与心血管功能生化标志物的相关性。
68例接受体外循环冠状动脉手术的糖尿病患者静脉注射20mg/kg体重的L-肉碱（LC）、24mg/kg体重的丙酰-L-肉碱（PC）或安慰剂（对照组）。术中测定动脉血、冠状窦血和心脏活检组织中的内皮素和核苷酸代谢产物。
与对照组（2.92±0.13和2.91±0.16L/min/m²；P分别为0.04和0.01）相比，体外循环后6小时和12小时时，PC组的心脏指数显著更高（3.30±0.12和3.47±0.15L/min/m²）。与对照组（23.5±0.75和23.4±0.75mmHg；P分别为0.03和0.02）相比，PC组在6小时（20.8±0.91mmHg）和12小时（20.7±0.81mmHg）时的平均肺动脉压更低。再灌注时对照组的跨心脏内皮素差值（0.33±0.26pmol/L）高于LC组（-0.61±0.24pmol/L，P=0.012），且有高于PC组（-0.29±0.17pmol/L，P=0.056）的趋势。再灌注10分钟后，对照组的跨心脏次黄嘌呤差值（6.22±1.08μmol/L）显著高于LC组（3.17±0.66μmol/L，P=0.025）和PC组（2.36±0.73μmol/L，P=0.006）。PC组的心肌次黄嘌呤浓度最低。
在接受体外循环冠状动脉手术的糖尿病患者中，给予丙酰-L-肉碱后血流动力学有显著改善，同时跨心脏内皮素差值降低，再灌注期间次黄嘌呤快速清除，提示代谢或血管功能得到改善。
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