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.     

Comparative study on cerebral injury after open heart surgery in patients with congenital and rheumatic heart disease

Alongwiththedevelopmentofscienceandtechnology,intracardiacoperationsbecomemuchsaferthanever.Althoughthemortalityrateofthepatientsreceivingintracardiacoperationwith helpofcardiopulmonarybypass(CPB)hasdecreased butneurologicalcomplicationsoccurfrequently.Neurologicalcomplicationshavebeenidentifiedsince theearlydayswhenemployingcardiacsurgery.1And neurologicalcomplicationsaftertheemploymentofCPB areimportantfatalcomplicationsofnon cardiovascular originatpresent.2Theincidenceofneuropsychologica…     

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.     

心内直视手术期间血浆P物质的变化

目的：了解血浆Ｐ物质（ＳＰ）在心内直视手术期间的水平变化。方法：采用放免法对１２例心内直视手术患者的血浆ＳＰ浓度分别在麻醉前、麻醉后、转机前、转机中、转机后、术毕及术后第二天七个时间点进行了动态观察。结果：在体外循环期间血浆ＳＰ水平非常显著高于麻醉前基础值（Ｐ＜０．０１）。结论：ＳＰ参与了体外循环心内直视手术期间心血管活动的调节。     

Usefulness of ulinastatin as a radical scavenger for protection of reperfusion injury after myocardial ischemia in open heart surgery]

The usefulness of ulinastatin for protection of reperfusion injury after myocardial ischemia was evaluated in 25 patients undergone open heart surgery (18 cases with coronary artery bypass grafting and 7 with valve replacements). Twenty five patients were divided into two groups; U (+)-group consisted of 12 patients with ulinastatin (10,000 IU/kg) injected via the aortic root just before aortic declamping, and U (-)-group of 13 patients without ulinastatin. There were no significant differences between the two groups in age, body weight, total cardiopulmonary bypass (CPB) time, and aortic cross clamp time. Blood samples were obtained from coronary sinus before the start of CPB, just before the aortic cross clamp and immediately after reperfusion, and 1 and 3 hours later. Levels of thiobarbituric acid (TBA), alpha-tocopherol (alpha TOC), polymorphonuclear elastase (PMNE), creatine phosphokinase (CK) and creatine phosphokinase isoenzyme (CK-WB) release were measured, and myocardial aerobic metabolism was also evaluated. At each time point after reperfusion, TBA levels in U (+)-group were significantly less (p less than 0.05), and alpha TOC levels were significantly higher (p less than 0.05) than those in U (-)-group. PMNE increased progressively during CPB and showed a peak at 3 hours after reperfusion. And both groups showed increased lactate production and anaerobic metabolism immediately after reperfusion and 1 hour later, as evidenced by changes in excess lactate and redox potential of lactate and pyruvate. There was, however, no significant difference between the two groups with CK-MB as well as CK release.(ABSTRACT TRUNCATED AT 250 WORDS)     

Temporal synthesis and release of endothelin within the systemic and myocardial circulation during and after cardiopulmonary bypass: relation to postoperative recovery

OBJECTIVE: To determine endothelin levels in arterial, pulmonary, and myocardial vascular compartments in patients undergoing coronary artery bypass graft surgery and to examine the influence of endothelin on postoperative recovery. DESIGN: Prospective, clinical study. SETTING: University hospital. PARTICIPANTS: Fifty patients undergoing elective coronary artery bypass graft surgery. INTERVENTIONS: Endothelin plasma content (fmol/mL) was measured in 50 patients undergoing coronary revascularization from various vascular compartments before surgery and at specific intervals up to 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Myocardial endothelin gradient (coronary sinus - aorta) was calculated before cardiopulmonary bypass (CPB), at release of the aortic cross-clamp, immediately after CPB, and 0.5 hour after CPB. The requirement for inotropic therapy and duration of patient stay in the intensive care unit were determined. Systemic and pulmonary endothelin levels were increased by >80% immediately after CPB when compared with preoperative values and increased again by approximately 60% during the first 24 hours postoperatively (p < 0.05). The myocardial endothelin gradient was reversed after CPB, indicating myocardial production of endothelin (pre-CPB, -0.72+/-0.39 fmol/mL v 0.5 hour post-CPB, 0.60+/-0.49 fmol/mL; p < 0.05). Longer intensive care unit times (>28 hours) were associated with higher systemic endothelin levels when compared with shorter times (<18 hours) (16.30+/-1.33 fmol/mL v 9.81+/-1.67 fmol/mL; p < 0.05). Patients with higher endothelin levels 6 hours postoperatively had greater inotropic requirements during the intensive care unit period. CONCLUSION: Endothelin levels after CPB remained persistently increased for at least 24 hours after surgery and were associated with increased myocardial production of endothelin. These results suggest that the increased endothelin observed in the early postoperative period may contribute to a complex recovery from coronary artery bypass graft surgery.     

Plasma hepatocyte growth factor levels after open heart surgery for congenital heart disease

BACKGROUND: Hepatocyte growth factor (HGF) is a polypeptide which acts protectively against endothelial cell dysfunction. A high plasma level of HGF is shown when the endothelium is injured. We measured plasma HGF levels during and after open heart operations for congenital heart disease, to elucidate its involvement with endothelial cell injury. METHODS: Experimental design: prospective study. Setting: perioperative setting. Patients: 18 children electively operated upon for congenital heart disease using CPB. RESULTS: Plasma HGF levels (ng/ml) before cardiopulmonary bypass (CPB) were 0.36+/-0.07 in 10 children (S-group) who were older and with simpler diseases, and 0.48+/-0.12 in 8 children (C-group) who were younger and with relatively complex diseases. HGF levels significantly increased after CPB, and gradually decreased thereafter. Plasma HGF levels 3 and 6 hours after CPB were significantly greater in the C-group than in the S-group (1.13+/-0.12 vs 1.68+/-0.1 6 3 hours after, and 1.09+/-0.19 vs 2.35+/-0,43 6 hours after; p<0.05 for both). There were significant positive correlations between HGF levels 6 hours after CPB and the duration of the CPB, the aortic crossclamping time, and plasma thrombomodulin levels just after CPB in all patients (p<0.05 for all). CONCLUSIONS: This data suggests that increased HGF levels are associated with endothelial cell injury induced by CPB, and that the increases are much greater in younger patients with complex anomalies.     

Effects of ulinastatin on changes of plasma granulocyte elastase, myeloperoxidase and fibronectin during and after open heart surgery

We investigated effects of ulinastatin on plasma levels of granulocyte elastase in alpha 1-proteinase inhibitor complex, myeloperoxidase and fibronectin in 20 patients during and after open heart surgery. Ulinastatin, 300,000 units were given immediately after the induction of anesthesia. Plasma fibronectin increased significantly after cardiopulmonary bypass (CPB) in ulinastatin group (group U) compared with control (group C) group. Regression coefficients between CPB time and changes of plasma fibronectin in group U were significantly different from those in group C after CPB. Plasma levels of granulocyte elastase in alpha 1-proteinase inhibitor complex were not different between the two groups. Regression coefficients of group U were smaller than those of group C after CPB. Plasma levels of myeloperoxidase were not different between the two groups. Regression coefficients of group U were significantly smaller than those of group C. Ulinastatin suppressed significantly the decrease of plasma fibronectin after CPB. Ulinastatin had no effects on plasma granulocyte elastase in alpha 1-proteinase inhibitor complex during and after CPB. Ulinastatin inhibited the increase of plasma myeloperoxidase in proportion to CPB time.     

常温不停跳心内直视手术冠脉血心肌酶、SOD、GHS及LPO的变化

目的 观察常温沁脏不停跳心内直视手术与冷停跳手术患者冠脉血心肌酶、超氧化物歧化酶（ＳＯＤ）、谷胱甘肽（ＧＳＨ）、脂质过氧化物（ＬＰＯ）的变化，明确不停跳手术对心肌保护作用。方法 ３６例心内直视手术患者随机分成不停跳与冷停跳组，每组１８例。不停跳组分别于体外循环前、体外循环１５分钟、体外循环停止时、机停后３０、６０分钟采血。冷停跳组分别于体外循环前、主动脉阻断时、主动脉开放时、开放后３０、６０分钟采     

Effects of nitroglycerin upon myocardial metabolism after open heart surgery

The effects of intravenous administration of nitroglycerin (TNG) on hemodynamics and myocardial metabolism after open heart surgery were evaluated in 22 patients without ischemic heart disease. On 12 hours after starting the continuous infusion of TNG at a rate of 0.2 micrograms/kg/min on 10 patients (TNG group), coronary blood flow (CBF) increased (p less than 0.01) and myocardial oxygen metabolism improved remarkably. However, anaerobic metabolism still existed in TNG group and no significant difference between TNG group and Control group even after 12 hour continuous drug infusion. From these studies, it was concluded that the intravenous administration of TNG at a rate of 0.2 microgram/kg/min increased CBF, however did not improve myocardial metabolism after open heart surgery possively probably because of changes in coronary collateral function.     

心脏直视手术患儿主动脉开放前低钙血症对心肌缺血再灌注损伤的影响

目的 探讨心脏直视手术患儿主动脉开放前低钙血症对心肌缺血再灌注损伤的影响.方法 选择拟在体外循环下行房缺或室缺修补术患儿50例,年龄6月～4.5岁,体重5～15 kg,根据主动脉开放前血浆离子钙浓度,将患儿分为低钙组(＜1.0 mmol/L)和常钙组(≥I.0 mmol/L),观察2组患儿心脏复跳情况.分别于CPB前、停CPB后即刻、停CPB后12 h时抽取桡动脉血1.5 ml,测定血浆离子钙浓度和动脉血气;于上述时点同时抽取中心静脉血3 ml,测定血浆肌钙蛋白I(cTnI)浓度.结果 在主动脉开放前患儿低钙血症发生率为72%,低钙组较常钙组患儿年龄小,体重轻(P＜0.05),而心脏复跳时间、室颤率、辅助循环时间、拔除气管导管时间、ICU监护时间和血浆cTnI浓度两组间差异无统计学意义(P＞0.05).结论 体外循环心脏直视手术患儿主动脉开放前低钙血症对心肌缺血再灌注损伤无影响.     

Dose the serum brain natriuretic peptide (BNP) level after open heart surgery reflect myocardial protection?

This clinical study was conducted to determine whether the serum BNP level after open heart surgery reflects myocardial protection. The levels of BNP and CPK-MB were measured before and after 12 hours of cardiopulmonary bypass, then 1, 3, and 6 days after open heart surgery, and the relationship between the maximum levels of BNP and the CPK-MB after open heart surgery was examined. The patients were divided into two groups according to whether or not the maximum CPK MB was more than 100 IU/l after open heart surgery. A significant relationship between the maximum BNP and the maximum CPK-MB after open heart surgery was observed (p = 0.013). Moreover, the BNP was significantly increased in the group of patients with a maximum CPK-MB > or = 100 IU/l, compared to that in those with a maximum CPK-MB < 100 IU/l, 12 hours 1 day, and 6 days after open heart surgery (p < 0.01). These findings indicate that the serum level of BNP after open heart surgery can reflect myocardial protection.     

Amino acid and carnitine supplementation in haemodialysed children

Plasma carnitine, amino acids and lipids levels were studied in ten uraemic children treated with haemodialysis and given amino acid supplementation with and without carnitine. As carnitine is synthesised from lysine and methionine and has a significant influence on lipid metabolism, the relationship between these was examined. Amino acid supplementation (0.25 g/kg body weight) was started with the intention of improving the plasma amino acid pattern in these children and increasing the concentration of lysine, which is the substrate for carnitine synthesis. Amino acids were administered i. v. during dialysis and carnitine (25 mg/kg body weight i. v.) was administered after dialysis three times a week. Concentrations of most essential amino acids were decreased in these patients. The first period of amino acid supplementation did not increase plasma levels of the essential amino acids, with the exception of tyrosine (P<0.01). After the second period of supplementation, methionine was increased (P<0.01), isoleucine was decreased (P<0.01), but tyrosine normalised and was significantly lower than after the first period (P<0.05). Thus overall amino acid supplementation did not improve amino acid levels; it was inconsistently associated with a further decrease in highdensity lipoprotein-cholesterol and an increase in total protein levels. Lysine concentrations after amino acid supplementation remained low. Paradoxically, before carnitine supplementation a positive correlation between free carnitine and triglycerides was observed. The plasma carnitine concentration, initially very low, was excessively high after carnitine supplementation. After carnitine administration no amelioration of any of the other biochemical indices was observed. Carnitine supplementation was associated with a significant reduction of total protein levels (P<0.01). In children with end-stage renal disease on haemodialysis, neither amino acid nor carnitine supplementation appear to result in significant improvements in plasma levels of essential amino acids or lipids.     

冷温血停搏液联合灌注对瓣膜置换术中炎性细胞因子和自由基的影响

目的　评价冷温血停搏液联合灌注在瓣膜置换术中对血浆促炎性细胞因子和自由基代谢水平的影响 ,探讨更有效的心肌保护方法。方法　将 30例瓣膜病病人随机分为两组 :温血组 (A组 ,n =15 ) ,采用温血诱导心脏停搏、冷血维持与终末温血灌注心肌保护方法 ;冷血组 (B组 ,n =15 ) ,采用冷氧合血停搏液进行心肌保护。分别于心肺转流 (CPB)前 (T1)、CPB 30min(T2 )、CPB结束后30min(T3 )、4h(T4)、2 4h(T5)测定血浆白细胞介素 6 (IL 6 )、IL 8和MDA浓度及SOD活性。结果B组IL 6于T2 即升高 ,持续至T5;A组无明显变化 ,于T3 明显低于B组 (P <0 0 5 )。B组IL 8于T2升高 (P <0 0 1) ,至T3 达峰值 (P <0 0 1) ,于T5下降至基础值水平 ;A组在T3 ～T4较基础值明显升高 (P <0 0 5 ) ,于T2 ～T4均显著低于B组 (P <0 0 5 )。两组MDA均在T2 升高 ,持续至T4,但A组于T3 、T4显著低于B组 (P <0 0 5 )。B组SOD活性自T2 开始降低 ,持续至T4(P <0 0 1) ;A组无明显变化 ,且在T3 与B组比较有显著性差异 (P <0 0 5 )。结论　冷温血停搏液联合灌注对瓣膜病病人的心肌再灌注损伤的抑制效应优于冷血心脏停搏液。     

体外循环对血浆胰岛素分泌影响的观察

本文观察了１５例体外循环病人术中不同时期血浆胰岛素，血糖，肾上腺素及去甲肾上腺素改变。结果显示，尽管体外循环过程中血浆胰岛素和血糖溶液明显升高，但胰岛素／血糖比值明显下降，这提示胰岛素分泌功能降低或延迟。在影响胰岛素分泌的因素中，血浆肾上腺素浓度高可能起重要作用。     

小儿心内直视手术中心肺转流对雷米芬太尼药代动力学的影响

目的探讨心内直视手术中心肺转流(CPB)对雷米芬太尼药代动力学的影响。方法择期CPB下行心内直视手术的患儿40例,静脉注射雷米芬太尼后1、2、3、4、5、10、15、20、25、30、45、60、90、120、180min及其后每隔3h直至24h各抽取桡动脉血测定血浆雷米芬太尼浓度。同时,分别在CPB前、CPB后、开放升主动脉时及拔除主动脉插管时各采取动脉血测定血浆雷米芬太尼、白蛋白、总蛋白浓度和血细胞比容(Hct)。应用NONLIN软件分析药代动力学参数。结果CPB前血浆雷米芬太尼浓度-时间衰减曲线可用三室开放模型表示,血药浓度-时间曲线拟合非常满意(r=0.9947,P<0.01)。CPB后雷米芬太尼的血药浓度显著降低(P<0.01),血药浓度-时间曲线也拟合良好(r=0.9905,P<0.01)。CPB前后药代动力学参数比较差异无统计学意义。CPB后白蛋白、总蛋白浓度和Hct均显著降低(P<0.01)。结论CPB时雷米芬太尼的血药浓度下降,但是药代动力学参数无明显改变。血液稀释是雷米芬太尼血药浓度改变的原因之一。     

缺血预处理对心肌的保护作用

目的 探讨定量检测血清心肌肌钙蛋白I(cTnI)，并结合临床指标，评价心肌缺血预处理(IPC)对缺血心肌的保护作用。方法 将40例择期心瓣膜置换术患者随机分为IPC组和对照组，每组20例。IPC组采用2个周期的3分钟缺血 5分钟再灌注方案。两组分别于体外循环(CPB)前、CPB后、术后l0小时、24小时、72小时和6天测定血清cTnI，比较两组间cTnI、术毕心脏自动复跳率、术后室性心律失常发生率、正性肌力药物使用率和死亡率。结果 术后两组cTnI均立即升高，对照组在术后l0小时达峰值，而IPC组在CPB后即达峰值；CPB前和术后6天两组cTnI比较差别无显著性意义(P＞0．05)，其余各时点对照组cTnI值均明显高于IPC组(P＜0．05)；对照组术后室性心律失常发生率和正性肌力药物使用率均明显高于IPC组(P＜0．05)。结论 IPC能降低缺血心肌血清cTnI浓度，降低患者术后室性心律失常发生率，减少术后正性肌力药物的使用率，对缺血心肌具有保护作用。     

Plasma magnesium in patients submitted to cardiac surgery and its influence on perioperative morbidity

BACKGROUND: To determine the changes in magnesaemia in cardiac surgical patients submitted to cardiopulmonary bypass (CPB) and their influence on perioperative morbidity. METHODS: Setting: the cardiovascular surgery department of a university hospital. Patients: 60 patients of both sexes, mean age 60+/-12 yrs, operated on consecutively for myocardial revascularization or valve replacement. Interventions: plasma Mg2+ levels were measured preoperatively, during CPB, postCPB and throughout the first 24 hrs after operation. Preoperative plasma Mg2+ levels of these patients were compared with those of 15 non-cardiac surgical patients and 11 healthy volunteers. RESULTS: Mean values of Mg2+ similar in the three populations although in the group of cardiac patients the number of hypomagnesaemic patients was significantly higher (16 patients=26.6%). In these 16 patients, preoperative hypomagnesaemia had a statistically significant relationship with the preoperative treatment with beta-blockers and previous history of arrhythmias (p<0.05). A progressive statistically significant decrease of Mg2+ was observed throughout the surgery that remained low at 24 hours postoperatively (p<0.05). Normomagnesemic patients needed significantly more shocks and electrical energy to obtain heart defibrillation after CPB. The incidence of both postoperative arrhythmias and postoperative low cardiac index (<2.5 L.m2) was statistically significantly more frequent in hypomagnesaemic patients (p<0.05). CONCLUSIONS: Preoperative hypomagnesaemia was more frequent in this small sample of cardiac surgical patients than in non-cardiac surgical patients and was related to preoperative treatment with b-blockers. Hypomagne-saemia caused by CPB persisted 24 hrs after operation and was associated with higher incidence of both postoperative arrhythmias and low cardiac index.     

甲状腺激素在体外循环心脏直视手术患者的应用

在体外循环（cardiopulmonary bypass,CPB）心脏直视手术后,患者常常发生伴有甲状腺激素血清水平严重降低的正常甲状腺病态综合征。然而,是否应该给实施CPB心脏直视手术的患者常规应用外源性甲状腺激素。以减轻手术中的心肌缺血一再灌注损伤和防治手术后正常甲状腺病态综合征的发生．目前尚无一致意见。本文综述正常甲状腺病态综合征及其相关不良影响、CPB心脏直视手术对甲状腺激素血清水平的影响和CPB心脏直视手术患者应用外源性甲状腺激素治疗等内容。     

Soluble Adhesion Molecules and Myocardial Injury during Coronary Artery Bypass Grafting

Abstract Cardiopulmonary bypass is acknowledged to be one of the major causes of a complex systemic inflammatory response after cardiac surgery. Leukocyte-endothelial binding followed by neutrophil migration appears to play a central role. These interactions are mediated by adhesion molecules on the surface of activated cells. The present study compared the perioperative levels of soluble adhesion molecules after coronary artery bypass grafting (CABG) in patients with or without cardiopulmonary bypass (CPB). Altogether, 9 patients underwent off-pump revascularization and 11 did so with CPB. Plasma levels of soluble adhesion molecules sE-selectin and sP-selectin and soluble intercellular adhesion molecule-1 (sICAM-1) were measured before anesthesia induction and 1, 4, and 20 hours after reperfusion to the myocardium. The baseline plasma levels of the adhesion molecules were similar in the two groups. Perioperative levels of sE-selectin remained the same and did not differ between groups. Plasma sP-selectin increased in both groups, the change being significantly greater in the CPB group than that in the off-pump group (p = 0.001). Plasma sICAM-1 decreased during an early stage after CABG with CPB, recovering at 4 hours after reperfusion; and a significant increase in ICAM-1 was observed 20 hours later. In the off-pump group, sICAM-1 levels did not change at 1 and 4 hours after reperfusion but increased 20 hours later. Postoperative creatine kinase–muscle bound (CK-MB) levels were significantly higher in the CPB group than in the off-pump group (p = 0.001). The change in sP-selectin levels also showed a correlation with CK-MB values (r = 0.676, p = 0.001). The results indicated that off-pump revascularization is associated with reduced endothelial activation and myocardial injury.