左卡尼汀在全肠外营养中的应用

一、概述左卡尼汀（l－carnitine）又称左旋肉碱，是一种广泛存在于机体组织内的特殊氨基酸，化学名L－３－羟－４－三甲氨基丁酸，商品名贝康亭，相对分子质量为１６２。二、来源人体左卡尼汀主要由两个途径获得。１．生物合成：参与合成或与合成有关的６种重要因子有：赖氨酸、蛋氨酸、烟酸、维生素B６、维生素C和Fe２＋，赖氨酸形成左卡尼汀的基本骨架。２．食物来源：肉类食品含较丰富的左卡尼汀，而植物类食物含量较低。果汁中几乎不含左卡尼汀，肌肉中含量很高。三、药理作用在机体内，左卡尼汀的基本功能是辅助长链脂肪酸穿透线粒…     

左卡尼汀在男性不育中临床应用专家共识(2014版)

<正>左卡尼汀(Levocarnitine),是哺乳动物能量代谢中必需的一种天然存在的物质,临床适应证为防治左卡尼汀缺乏,随着左卡尼汀临床应用及研究的不断深入,其在提高精子活力、改善附睾功能、治疗男性不育方面的疗效和安全性得到了广大临床医生的认可,已经成为目前男性不育治疗领域的常用药物[1]。2007年中华医学会《男性不育诊治指南》中已明确了左卡尼汀在男性不育治疗中的重要价值[1],但目前仍存在适应证不明确,使用疗程不当,用药方法不规范等问题。为规范其在男性不育治疗     

左卡尼汀对乳腺癌化放疗心脏毒性的保护

左卡尼汀可以改善阿霉素所致的卡尼汀系统代谢变化,能显著阻止或减低阿霉素等抗癌药物诱发的急慢性心肌病变的发生,减少抗癌药物对心脏的毒性[1].我们设计了本研究观察左卡尼汀对左侧乳腺癌患者术后接受化放疗心脏毒性的保护作用,现报道如下:     

左卡尼汀与清开灵注射液联用治疗急性病毒性心肌炎临床观察

目的探讨左卡尼汀联合清开灵注射液治疗急性病毒性心肌炎的临床效果。方法将急性病毒性心肌炎患者98例随机分为观察组与对照组,治疗组50例,应用左卡尼汀和清开灵,对照组48例,给予能量合剂和病毒唑,比较两组的疗效。结果治疗组临床表现、心电图、心肌标志物治疗后的改善与对照组治疗后比较,差异有统计学意义（P〈0.05）。结论左卡尼汀联合清开灵注射液治疗急性病毒性心肌炎疗效显著,值得临床推广。     

血液透析前补充左卡尼汀对改善终末期尿毒症患者透析耐受性的影响

目的 探讨不同时段静脉补充左卡尼汀对终末期维持性血液透析患者透析过程中发生低血压、肌肉痉挛及透析患者耐受性的影响和血浆游离肉碱浓度变化.方法 选择终末期维持性血液透析患者30例,按照数字表法随机分为3组:A组为对照组(透析结束后给予左卡尼汀1.0g加入0.9％氯化钠20ml静脉注射)10例,B组(透析前给予左卡尼汀1.0g加入0.9％氯化钠20ml静脉注射,透析结束后左卡尼汀1.0g加入0.9％氯化钠20ml静脉注射)10例,C组(透析开始2h后给予左卡尼汀1.0g加入0.9％氯化钠20ml静脉注射,透析结束后给予左卡尼汀1.0g加入0.9％氯化钠20ml静脉注射)10例.观察各组用药前、用药4周、8周及12周后各项指标的变化、血浆肉碱浓度和血液透析充分性.结果 B、C两组患者较对照组临床症状及分级显著好转,差异有统计学意义(P＜0.05);游离血浆肉碱浓度较对照组升高,差异有统计学意义(P＜0.05);患者透析的耐受力和尿素氮清除效率(Kt/V)明显好转,差异有统计学意义(P＜0.05).结论 在透析前或透析中给予左卡尼汀即刻补充剂量能降低患者发生透析不良反应的风险,增加患者的透析耐受力,提高患者透析的充分性.     

左卡尼汀对高原地区维持性血液透析患者营养状况的影响观察

维持性血液透析（MHD）患者补充外源性左卡尼汀是改善营养状态的一种有效治疗方法。据国内相关文献报道[1,2]补充外源性左卡尼汀可改善维持性血液透析患者营养状态。然而这些研究均没有对处于高海拔地区MHD患者进行相关研究。为探讨高原地区MHD患者补充外源性左卡尼汀的营养状况的影响,     

左卡尼汀对血液透析患者微炎症及营养状况的影响

目的探讨左卡尼汀对维持性血液透析患者微炎症及营养状况的影响。方法选择62例维持性血液透析患者,随机分为左卡尼汀组和对照组,检测二组患者治疗前、治疗后血C反应蛋白（CRP）、血红蛋白（Hb）、白蛋白（Alb）和血肌酐（SCr）值,计算Kt／V值。结果与治疗前及对照组治疗后比较,左卡尼汀组患者治疗后CRP水平下降,Alb、Hb升高,差异有统计学意义（P〈0．05）;对照组患者治疗前后CRP、Alb、Hb无统计学差异（P〉0.05）;二组患者治疗前后SCr、Kt/V值均无统计学差异（P〉0．05）。结论左卡尼汀可减轻维持性血液透析患者微炎症反应,改善患者营养状态。     

左卡尼汀治疗特发性少、弱精子症疗效及安全性的系统评价

目的:根据现有临床证据评价左卡尼汀治疗特发性少、弱精子症的疗效及安全性。方法:通过计算机检索建库至2014年4月期间Cochrane图书馆、Pub Med、MEDLINE、EMBASE、CNKI、VIP、CBM、万方数据库,辅以手工检索有关左卡尼汀治疗特发性少、弱精子症的文献,根据纳入与排除标准筛选文献、提取资料和评价纳入研究的方法学质量后,采用Rev Man5.2软件对数据进行meta分析。结果:纳入7个随机对照试验(RCT),共计751例特发性少、弱精子症患者,排除失访人数后实际纳入678例。meta分析结果显示:左卡尼汀治疗后配偶自然妊娠率高于对照组[RR=3.2,95%CI(1.74,5.87),P=0.000 2];左卡尼汀治疗12~16周和24~26周后精子活动率[WMD=5.21,95%CI(2.78,7.64),P<0.000 1;WMD=9.29,95%CI(1.28,17.29),P=0.02]、前向运动精子百分率[WMD=12.44,95%CI(4.58,20.31),P=0.002;WMD=9.76,95%CI(3.56,15.97),P=0.002]均高于对照组;左卡尼汀治疗12~16周和24~26周后精子浓度与对照组比较差异无统计学意义[WMD=4.91,95%CI(-2.63,12.45),P=0.2;WMD=0.93,95%CI(-3.48,5.34),P=0.68];左卡尼汀治疗12~16周后畸形精子百分率低于对照组[WMD=-2.48,95%CI(-4.35,-0.61),P=0.009],而左卡尼汀治疗24~26周后畸形精子百分率与对照组比较差异无统计学意义[WMD=-4.38,95%CI(-9.66,0.89),P=0.1];左卡尼汀治疗12~16周和24~26周后精液量与对照组比较差异无统计学意义[WMD=-0.13,95%CI(-0.43,0.18),P=0.42;WMD=0.28,95%CI(-0.02,0.58),P=0.07];其中4项研究报告了左卡尼汀治疗期间均无严重不良反应发生。结论:基于当前证据,左卡尼汀可能对特发性少、弱精子症患者配偶的自然妊娠率及患者的精液质量有一定的改善,无明显不良反应。     

仙鹿口服液联合左卡尼汀口服液治疗精子DNA损伤的临床观察

目的研究联合应用左卡尼汀口服液(东维力)及仙鹿口服液治疗男性精子DNA损伤的临床疗效及其用药安全性。方法选取200例精子DNA碎片率(DFI值)高于25%的男性,随机分为4组进行治疗。A组口服左卡尼汀+仙鹿口服液,B组口服左卡尼汀口服液,C组口服仙鹿口服液,D组不进行药物干预,共计3个月,3个月后复查精子DNA完整性及精液常规参数,比较DFI改善程度、精子密度及活力的改善及用药期间安全性。结果仙鹿口服液联合左卡尼汀口服液治疗组与使用单药组及不用药组相比,治疗精子DNA损伤的有效率比较差异均有统计学意义;对a级精子百分率提升的有效率比较差异亦有统计学意义:临床安全性各组间比较未见统计学差异。结论联合应用左卡尼汀+仙鹿口服液治疗精子DNA损伤较使用单药及不用药物更为有效,精子密度及a级精子百分率亦有明显改善,临床安全性高,具有较高的临床应用价值。     

左卡尼丁治疗血液透析中的低血压疗效观察

目的:观察管通治疗血液透析中的低血压疗效.方法:观察左卡尼汀联合管通治疗12周,对30例透析性顽固性低血压患者的疗效.结果:治疗后透析过程中血压下降幅度明显减小,与治疗前比较差异显著(P<0.01).结论:左卡尼汀联合管通对透析性顽固性低血压疗效显著.     

Plasma carnitine concentrations in patients undergoing open heart surgery.

Carnitine is an essential cofactor for fatty acid (FA) metabolism, the predominant source of ATP in the normal aerobic heart. During myocardial ischemia, FA metabolism is impaired and tissue carnitine levels are depleted. Since the heart cannot synthesize carnitine, plasma carnitine could play an important role in maintaining myocardial carnitine levels during reperfusion. The purpose of this study was to determine the incidence of abnormal plasma carnitine concentrations in open heart surgery. Blood samples were obtained from eleven patients before, immediately after, and two hours after cardiopulmonary bypass (CPB). Total and free carnitine levels were significantly reduced immediately after CPB (p<0.01) and remained depressed until two hours after CPB (p<0.01 vs. pre CPB), while acyl carnitine levels were unchanged over the course of this study. These depressed free carnitine levels might affect cardiac metabolism in the heart after open heart surgery. Carnitine supplement might be a useful adjunct in the therapy after open heart surgery.     

Carnitine supplementation vs. medium-chain triglycerides in postburn nutritional support

The effect of dietary supplementation of carnitine on protein metabolism was studied in a burned guinea-pig model. Animals bearing a 30 per cent total body surface area burn were enterally infused with three isocaloric and isonitrogenous diets via gastrostomy feeding tubes for 14 days. Two diets contained safflower oil (long-chain triglycerides, LCT) and another diet contained medium-chain triglycerides (MCT) as their lipid sources (30 per cent of total calories as lipid). L-Carnitine was added to one of the two diets containing safflower oil. There were no significant differences in nitrogen balance, urinary excretion, serum albumin or transferrin among the three groups. However, the use of MCT in place of LCT appeared to increase liver weight and liver nitrogen. In this model, carnitine supplementation did not enhance the nitrogensparing effect of fat following burn injury.     

Carnitine and carnitine esters in acute renal failure

Plasma concentrations of carnitine and carnitine esters were determined in patients with multiple forms of acute renal failure with and without sepsis, and also before and after haemodialysis therapy. Total carnitine, free carnitine, short-chain and long-chain acylcarnitine values of both groups of acute renal failure patients were markedly elevated compared with healthy subjects and chronically uraemic patients undergoing regular haemodialysis treatment. Carnitine and carnitine esters did not differ between septic and non-septic patients before and after haemodialysis with dialysers made of cuprophane or polysulphone. Animal experiments with acutely uraemic rats were performed in order to determine whether the liver or the kidney may be responsible for elevated carnitine and carnitine esters in acute renal failure. Plasma and liver total carnitine, free carnitine, short-chain acylcarnitine and long-chain acylcarnitine were significantly elevated in sham-operated animals, and further in ureter ligated and bilateral nephrectomised rats. Skeletal muscle and heart muscle carnitine and carnitine esters remained the same as in sham-operated controls. Our data demonstrate markedly increased liver carnitine synthesis and carnitine acylation in an acute uraemic rat model even after binephrectomy and 48-h food depletion and in the presence of elevated serum carnitine concentrations. Furthermore, from our clinical study we conclude that there is no need for carnitine supplementation in patients who developed acute renal failure in the postoperative and post-traumatic state under adequate nutrition even when requiring daily haemodialysis.     

Evaluation of plasma carnitine levels after orthotopic transplantation of the liver

Variations in plasma levels of total carnitine (TC), free carnitine (FC), and acyl-carnitine (AC) were studied in 10 patients undergoing orthotopic liver transplantation. The postoperative values were higher than the preoperative ones and positively related to time flow. As exogenous carnitine was not supplied during the study, these data suggested a better biosynthetic activity in the transplanted liver, in spite of standard blood tests results. No positive correlation between carnitine levels and variations in serum transaminases, bilirubin, cholestasis related enzymes, pre-albumin and albumin supply was found. Carnitine plasma levels were not influenced either by nutritional caloric input or by methionine and lysine inputs. Our results show that variations in carnitine plasma levels are a specific and responsive index of functional recovery in the transplanted liver.     

Effects of carnitine on cardiac function after cardioplegic ischemia in neonatal rabbit hearts

BACKGROUND: Ischemia immediately impairs myocardial fatty acid metabolism and reduces the concentration of carnitine which is an essential cofactor for fatty acid metabolism in the mitochondria. The purpose of this study was to investigate the effects of carnitine administration on recovery of cardiac function after cardioplegic ischemia in the neonatal heart where fatty acid metabolism is not a predominant source of adenosine triphosphate. METHODS: Isolated blood-perfused neonatal rabbit hearts underwent 3 hours of cold cardioplegic ischemia. The control group (n = 10) was reperfused with unmodified diluted blood. The carnitine group (n = 10) was reperfused with the blood containing 5 mM/L of carnitine. Before ischemia (base line) and after 15 and 30 minutes reperfusion, left ventricular (LV) function and LV compliance were measured using a intraventricular conductance catheter combined with an isovolumic balloon. Coronary blood flow was measured and myocardial oxygen consumption was calculated. RESULTS: Carnitine significantly improved not only LV systolic function but also LV diastolic function (p < 0.05) as well as LV compliance after ischemia. Coronary blood flow and myocardial oxygen consumption were significantly improved after ischemia in the carnitine group compared with the control group (p < 0.05). CONCLUSIONS: These results suggest that carnitine strikingly improves LV functional recovery and aerobic metabolism after cold cardioplegic arrest, and may improve cardiac performance in neonates after open heart surgery.     

Myocardial function, energy provision, and carnitine deficiency in experimental uremia

Cardiac complications are the leading cause of mortality in patients with chronic renal failure. Secondary carnitine deficiency, which is frequently observed in hemodialysis patients, has been associated with cardiac hypertrophy and heart failure and may impair myocardial fatty acid oxidation. In chronic kidney disease, impaired carnitine homeostasis also may affect myocardial metabolism. In this study, myocardial function and substrate oxidation in conjunction with carnitine deficiency were investigated in experimental renal failure. Uremia was induced in male Sprague-Dawley rats via a two-stage five-sixths nephrectomy. Cardiac function and substrate oxidation were assessed in vitro by means of isovolumic perfusion using 13C nuclear magnetic resonance at 3 and 6 wk of uremia. Renal impairment as assessed by serum creatinine was more severe initially and was associated with a significant deficiency in serum free carnitine (43%; P < 0.001) and elevated acyl carnitine/free carnitine ratio. Myocardial tissue carnitine concentrations, however, were unaffected. A moderate degree of cardiac hypertrophy (10 to 14%; P < 0.05) was observed in uremia without evidence of dysfunction or changes in myocardial substrate utilization. It is concluded that renal dysfunction is associated with cardiac hypertrophy in the presence of normal myocardial carnitine levels, despite a significant depletion in serum carnitine. This may be a factor in maintaining normal cardiac function and metabolism.     

Carnitine Contents in Remnant Liver, Kidney, and Skeletal Muscle after Partial Hepatectomy in Rats: Randomized Trial

p < 0.01). The increase of total carnitine content was more obvious than that of the free form. In contrast, the decreasing concentrations of total carnitine and free carnitine in the kidney were significant ( p < 0.01). In skeletal muscle the total carnitine content decreased to a small extent, and it was observed only at 6 hours after partial hepatectomy ( p < 0.05). It is suggested that remnant liver promoted the generation of carnitine, whereas kidney and skeletal muscle released their stored carnitine at an early stage after partial hepatectomy. As a result, the influx of the carnitine into hepatocytes increased at the regenerative stage. The carnitine content of remnant liver is sufficient during the early posthepatectomy stage.     

Carnitine affects fatty acid metabolism after cardioplegic arrest in neonatal rabbit hearts

BACKGROUND: Fatty acid (FA) metabolism and the contribution of carnitine to metabolism after cardioplegic arrest still remain unclear, especially in the neonatal heart where beta-oxidation is not a predominant source of adenosine triphosphate. METHODS: FA metabolism and the effects of carnitine administration were evaluated using a newborn (7-day-old) rabbit blood-perfused Langendorff model subjected to cold cardioplegic arrest. The hearts were divided into five groups; (1) perfused with unmodified diluted blood (n = 9), (2) subjected to 180 minutes of cold cardioplegic arrest and reperfused with the blood (n = 9), (3) subjected to the same ischemia and reperfused with the blood containing 40 microM/L (n = 9), (4) 0.5 mM/L (n = 5), and (5) 5 mM/L of carnitine (n = 5). During reperfusion, FA metabolism was assessed by iodine-123-labeled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid, a fatty acid. The myocardial time-radioactivity curve was then determined and a mathematical compartment analysis of the external detection was used to elucidate FA metabolism in the cardiac myocyte. RESULTS: Cold cardioplegic arrest resulted in significantly impaired FA metabolism following reperfusion. Compartment analysis suggested that FA activation in the cytosol and beta-oxidation were impaired. Carnitine supplementation in groups 3 and 4 improved FA metabolism during reperfusion. In contrast, supplementation in group 5 had no beneficial effect on FA metabolism. CONCLUSIONS: These results suggest that FA metabolism is impaired after cold cardioplegic arrest and that carnitine supplementation may improve aerobic metabolism in neonates after open heart surgery.     

L-Carnitine in Dialysis Patients

Hemodialysis (HD) patients often have low serum concentrations of free L‐carnitine and decreased skeletal muscle stores. As L‐carnitine is an essential cofactor in fatty acid and energy metabolism, it is possible that abnormal carnitine metabolism in dialysis patients may be associated with clinical problems such as skeletal myopathies, intradialytic symptoms, reduced cardiac function, and anemia. Studies have shown that L‐carnitine supplementation in HD patients improves several complications seen in dialysis patients, including cardiac complications (arrhythmias, reduced output, low cardiothoracic ratio), limitation of exercise capacity, increased intradialytic hypotension, and muscle symptoms. The most promising results have been noted in the treatment of erythropoietin‐resistant anemia. Routine administration of L‐carnitine to all dialysis patients is not recommended at this time; however, a therapeutic trial of L‐carnitine can be useful in symptomatic patients with certain clinical features unresponsive to the usual measures. These include intradialytic muscle cramps and hypotension, asthenia, cardiomyopathy, lowered ejection fraction, muscle weakness or myopathy, reduced oxygen consumption, and anemia requiring large doses of EPO.     

Multicenter trial of L-carnitine in maintenance hemodialysis patients. I. Carnitine concentrations and lipid effects

Previous studies have reported conflicting results of carnitine supplementation on plasma lipids in patients with chronic renal failure. We therefore performed a four center, double-blind placebo controlled trial to evaluate the effects of post-hemodialysis intravenous injection of L-carnitine in ESRD patients on maintenance hemodialysis. Thirty-eight patients received up to six months of L-carnitine infusions (20 mg/kg) post-dialysis and 44 patients received placebo infusions. In both groups of patients, baseline pre-dialysis plasma and red blood cell total carnitine levels were normal, but pre-dialysis plasma-free carnitine concentrations and free/total ratios were subnormal, and plasma acyl levels were elevated. Post-dialysis plasma free and total carnitine concentrations were also subnormal. Plasma and red blood cell total carnitine levels rose eightfold in carnitine recipients, but were unchanged from baseline in those receiving placebo. There were no significant changes observed in plasma triglycerides, HDL-cholesterol or other lipoprotein parameters in either the carnitine or placebo treated groups. We conclude that carnitine metabolism is altered in uremia. Furthermore, in a randomly-selected hemodialysis population, L-carnitine injection at the dose of 20 mg/kg results in significant increases in blood (and perhaps tissue) carnitine levels, but this is not associated with any major effects on lipid profiles.