The clopidogrel after surgery for coronary artery disease (CASCADE) randomized controlled trial: clopidogrel and aspirin versus aspirin alone after coronary bypass surgery [NCT00228423]

Background

Saphenous vein graft disease remains a major limitation of coronary artery bypass graft surgery. The process of saphenous vein intimal hyperplasia begins just days after surgical revascularization, setting the stage for graft atherosclerotic disease and its sequalae. Clopidogrel improves outcomes in patients with atherosclerotic disease, and is effective at reducing intimal hyperplasia in animal models of thrombosis. Therefore, the goal of this study will be to evaluate the efficacy of clopidogrel and aspirin therapy versus aspirin alone in the prevention of saphenous vein graft intimal hyperplasia following coronary artery bypass surgery.

Methods

Patients undergoing multi-vessel coronary artery bypass grafting and in whom at least two saphenous vein grafts will be used are eligible for the study. Patients will be randomized to receive daily clopidogrel 75 mg or placebo, in addition to daily aspirin 162 mg, for a one year duration starting on the day of surgery (as soon as postoperative bleeding has been excluded). At the end of one year, all patients will undergo coronary angiography and intravascular ultrasound assessment of one saphenous vein graft as selected by randomization. The trial will be powered to test the hypothesis that clopidogrel and aspirin will reduce vein graft intimal hyperplasia by 20% compared to aspirin alone at one year following bypass surgery.

Discussion

This trial is the first prospective human study that will address the question of whether clopidogrel therapy improves outcomes and reduces saphenous vein graft intimal hyperplasia following cardiac surgery. Should the combination of clopidogrel and aspirin reduce the process of vein graft intimal hyperplasia, the results of this study will help redefine modern antiplatelet management of coronary artery bypass patients.     

Cardiopulmonary bypass reduces atrial Na+-K+-ATPase expression in children

Cardiopulmonary bypass (CPB) may induce serious side effects, potentially leading to myocardial failure. The Na(+)-K(+)-ATPase is a key component for myocardial function. Due to its developmental regulation, results from adult studies cannot be adopted to the situation in childhood. Right atrial myocardium from patients with left-to-right shunts at atrial level (VO, n=8) and those without (NO, n=8) was excised during heart surgery before and after CPB. Na(+)-K(+)-ATPase isoforms ATP1A1 (p=0.008) and ATP1A3 (p=0.038) decreased during CPB, which decrease was restricted to the VO group. This study highlights the importance of the underlying heart defect for susceptibility to the effects of CPB, showing a reduced Na(+)-K(+)-ATPase mRNA expression only in patients with left-to-right shunts on the atrial level. This seemed to be an early molecular event, as apart from one, none of the patients showed heart failure before or after surgery.     

Peptide YY levels are elevated after gastric bypass surgery

Objective: Mechanisms that promote effective and sustained weight loss in persons who have undergone Roux‐en‐Y gastric bypass surgery are incompletely understood but may be mediated, in part, by changes in appetite. Peptide YY (PYY) is a gut‐derived hormone with anorectic properties. We sought to determine whether gastric bypass surgery alters PYY levels or response to glucose. Research Methods and Procedures: PYY and ghrelin levels after a 75‐gram oral glucose tolerance test were measured in 6 morbidly obese patients 1.5 ± 0.7 (SE) years after gastric bypass compared with 5 lean and 12 obese controls. Results: After substantial body weight loss (36.8 ± 3.6%) induced by gastric bypass, the PYY response to an oral glucose tolerance test was significantly higher than in controls (p = 0.01). PYY increased ～10‐fold after a 75‐gram glucose load to a peak of 303.0 ± 37.0 pg/mL at 30 minutes (p = 0.03) and remained significantly higher than fasting levels for all subsequent time‐points. In contrast, PYY levels in obese and lean controls increased to a peak of ～2‐fold, which was only borderline significant. Ghrelin levels decreased in a symmetric but opposite fashion to that of PYY. Discussion: Gastric bypass results in a more robust PYY response to caloric intake, which, in conjunction with decreased ghrelin levels, may contribute to the sustained efficacy of this procedure. The findings provide further evidence for a role of gut‐derived hormones in mediating appetite changes after gastric bypass and support further efforts to determine whether PYY_3–36 replacement could represent an effective therapy for obesity.     

粪菌移植在体外循环术后肠道菌群失调患者中的应用

目的 研究粪菌移植在体外循环术后肠道菌群失调患者中的应用,探讨其有效性及安全性。方法 回顾性分析2015年1月—2017年12月兰大一院心外科重症监护室行粪菌移植治疗肠道菌群失调的患者20例,对比治疗前及治疗后患者降钙素原、肠道菌群失调程度、Hart腹泻计分的变化,统计痊愈率并随访1个月关注不良反应的发生。结果 与治疗前相比,粪菌移植治疗后所有患者降钙素原明显下降[（2.79±2.93）vs（0.83±0.86）ng/mL],Hart腹泻计分明显减少[（20.40±2.62）vs（4.15±2.70）],差异均具有统计学意义（Ps＜0.05）。治疗后患者肠道菌群失调程度明显改善（P＜0.05）。患者痊愈率达95%。治疗期间及随访1个月无不良反应发生。结论 粪菌移植可以明显改善体外循环术后患者肠道菌群失调情况及临床症状,降低患者炎症反应,且无不良事件发生,有利于患者术后康复,安全性好。     

Human DNA polymerases catalyze lesion bypass across benzo[a]pyrene-derived DNA adduct clustered with an abasic site

The combined action of oxidative stress and genotoxic polycyclic aromatic hydrocarbons derivatives can lead to cluster-type DNA damage that includes both a modified nucleotide and a bulky lesion. As an example, we investigated the possibility of repair of an AP site located opposite a minor groove-positioned (+)-trans-BPDE-dG or a base-displaced intercalated (+)-cis-BPDE-dG adduct (BP lesion) by a BER system. Oligonucleotides with single uracil residue in the certain position were annealed with complementary oligonucleotides bearing either a cis- or trans-BP adduct. Digestion with uracil DNA glycosylase was utilized to generate an AP site which was then hydrolyzed by APE1, and the resulting gap was processed by X-family DNA polymerases β (Polβ) and λ (Polλ), or Y-family polymerase ι (Polι). By varying reaction conditions, namely, Mg²⁺/Mn²⁺ replacement/combination and ionic strength decrease, we found that under certain conditions both Polβ and Polι can catalyze lesion bypass across both cis- and trans-BP adducts in the presence of physiological dNTP concentrations. Polβ and Polι catalyze gap filling trans-lesion synthesis in an error prone manner. By contrast, Polλ selectively introduced the correct dCTP opposite the modified dG in the case of cis-BP-dG adduct only, and did not bypass the stereoisomeric trans-adduct under any of the conditions examined. The results suggest that Polλ is a specialized polymerase that can process these kinds of lesions.     

Photorespiration in the context of Rubisco biochemistry,CO2 diffusion and metabolism

Photorespiratory metabolism is essential for plants to maintain functional photosynthesis in an oxygen‐containing environment. Because the oxygenation reaction of Rubisco is followed by the loss of previously fixed carbon, photorespiration is often considered a wasteful process and considerable efforts are aimed at minimizing the negative impact of photorespiration on the plant’s carbon uptake. However, the photorespiratory pathway has also many positive aspects, as it is well integrated within other metabolic processes, such as nitrogen assimilation and C₁ metabolism, and it is important for maintaining the redox balance of the plant. The overall effect of photorespiratory carbon loss on the net CO₂ fixation of the plant is also strongly influenced by the physiology of the leaf related to CO₂ diffusion. This review outlines the distinction between Rubisco oxygenation and photorespiratory CO₂ release as a basis to evaluate the costs and benefits of photorespiration.     

Angiotensin II,as well as 5-hydroxytriptamine,is a potent vasospasm inducer of saphenous vein graft for coronary artery bypass grafting in patients with diabetes mellitus

Diabetes mellitus (DM) is an important risk factor for adverse outcomes of coronary artery bypass grafting. The bypass grafts harvested from patients with DM tend to go into spasm after their implantation into the coronary circulation. To clarify the contribution of 5-hydroxytriptamine (5-HT) and angiotensin II (AngII) in the bypass graft spasm, we examined the contractile reactivity to 5-HT or AngII of isolated human endothelium-denuded saphenous vein (SV) harvested from DM and non-DM patients. The 5-HT-induced constriction of the SV was significantly augmented in the DM group than in the non-DM group, which is similar to our previous report. AngII-induced constriction of the SV was also significantly augmented in the DM group than the non-DM group. Especially in the non-DM group, the AngII-induced maximal vasoconstriction was markedly lower than the 5-HT-induced one. Meanwhile, the increasing rates of AngII-induced vasoconstriction in the DM group to the non-DM group were significantly greater than those of 5-HT-induced vasoconstriction. These results indicate that 5-HT is a potent inducer of SV graft spasm in both DM and non-DM patients, while AngII is a potent inducer of SV graft spasm only in patients with DM. Furthermore, the protein level of AngII AT₁ receptor (AT₁R), but not the protein level of 5-HT_2A receptor, in the membrane fraction of the SV smooth muscle cells of DM patients was significantly increased as compared with that of the non-DM patients. These results suggest that the mechanism for hyperreactivity to AngII in the SV from DM patients is due to, at least in part, the increase in the amount of AT₁R on membrane of the SV smooth muscle cells.     

体外循环超滤法影响小儿心内直视术患者血糖和血乳酸水平的研究

目的本研究旨在探讨体外循环超滤法对小儿心内直视术患者血糖和血乳酸的影响及临床意义.方法62例小儿先心病患者(男39例,女23例,体重9.5～20kg,年龄平均2.5岁)随机分成AB两组,A组用5%葡萄糖预充,B组无糖预充,各组再分成超滤组和对照组,两组病种基本相同.超滤组和对照组在复温前、停机时,分别采血和超滤液测定血糖和乳酸,进行对比.结果A组和B组超滤后血清中血糖相比(P＜0.01),两组统计学差异有显著性.超滤组与对照组血糖和乳酸浓度,无明显统计学差异.而超滤液中含有较高浓度糖和乳酸.结论无糖预充可以降低血糖和乳酸,用超滤法可直接排除心内直视术小儿患者高血糖和高乳酸,减少神经系统的受损,值得临床推广应用.     

胃转流术后远端肠黏膜形态及生长因子表达的变化

目的：探讨胃转流术后远端肠管黏膜的适应性变化及生长因子的表达情况。方法：将8周龄的Wistar大鼠随机分为对照组、假手术组和胃转流术组,术后8周取吻合口远端肠管行常规病理切片检查,测量肠黏膜厚度和绒毛高度,采用免疫荧光法检测肠粘膜中表皮生长因子（EGF）和胰岛素样生长因子-1（IGF—1）的表达。结果：胃转流术组黏膜厚度（672±39与500±31um,P〈0．01）和绒毛高度（445±19与342±15um,P〈0．01）均显著高于假手术组（P〈0．01）,而对照组和假手术组间均无显著差异。与假手术组比较,胃转流术组肠粘膜中EGF和IGF-1的表达显著升高（P〈0．01）,而对照组和假手术组间无显著差异。结论：胃转流术后远端肠管粘膜发生适应性增生,同时伴随着EGF和IGF—1表达水平的升高。     

犬体外循环模型建立及麻醉处理

目的建立CPB实验动物模型,加强围手术期麻醉管理,探索肺功能保护方法 ,以减少术后并发症的产生。方法 20只实验犬全部用于建立实验动物模型。丙泊酚复合麻醉后,开胸;全血肝素化后,连接体外循环管道开始体外循环,微量泵入丙泊酚50～150μg/（kg·min）维持麻醉;监测麻醉诱导前（T0）、气管插管即刻（T1）、CPB前即刻（T2）、降温至32.0℃（T3）、阻断主动脉前即刻（T4）、阻断主动脉后2min（T5）、开始复温即刻（T6）、停CPB即刻（T7）及停CPB后15min（T8）9个时间结点的鼻咽温度、平均动脉压（mean arterial pressure,MAP）及心率（heart rate,HR）。结果体外循环期间各时点鼻咽温度均低于T0及T2（P〈0.05）;T1、T2及体外循环期间各时点的MAP明显低于T0（P〈0.05）,体外循环期间各时点的MAP低于T2（P〈0.05）;T4的HR明显低于T0及T2（P〈0.05）。体外循环期间各时点MAP比较无统计学意义（P〉0.05）。结论犬体外循环模型建立的成败与手术技术和麻醉管理密切相关。