不同剂量异丙酚对心内直视手术患者肌钙蛋白I和血流动力学的影响

目的观察异丙酚对体外循环下行冠脉搭桥术患者心肌缺血再灌注损伤保护作用的剂量相关性,以及不同剂量对血流动力学的影响,寻求产生最佳心肌保护作用和使患者心功能得到最佳恢复的剂量。方法选择45例择期常规体外循环下行冠脉搭桥术患者,随机分成A、B、C三组。诱导后用微量注射泵持续输注异丙酚A组3 mg/(kg.h);B组5 mg/(kg.h);C组8 mg/(kg.h)直到手术结束。分别于体外循环前、主动脉开放后30min、6 h、24 h自桡动脉采血,测定血浆心肌肌钙蛋白I(cTnI)浓度。分别测定开胸前、主动脉插管前、停体外循环、关胸前、关胸毕的平均动脉压(MAP)、外周血管阻力指数(SVRl)、心脏指数,同时观察主动脉开放后的心脏自动复跳情况。结果三组从诱导至体外循环开始时间、体外循环时间、主动脉阻断时间、心肌保护方法以及心脏自动复跳情况无明显差异。三组患者cTnI水平于主动脉开放后迅速升高,主动脉开放后6小时处于高峰期。与A组比较,主动脉开放后B、C组患者cTnI值较低(P<0.01);B组与C组比较各时间点均无明显差异。三组患者停体外循环后心脏指数较开胸前升高明显(P<0.01),SVRI在停体外循环后均有下降(P<0.01),其中C组SVRI下降较其它两组显著,C组停体外循环后各时间点心脏指数值较B组要低(P<0.05)。结论在冠脉搭桥术中,异丙酚以5 mg/(kg.h)持续输注至术毕,能减轻体外循环中心肌缺血再灌注损伤,血浆cTnI水平较低,有较高的心脏指数和满意的SVRI,能维持较为理想的血流动力学。     

不同剂量异丙酚对心内直视手术患者肌钙蛋白Ⅰ和血流动力学的影响

目的 观察异丙酚对体外循环下行冠脉搭桥术患者心肌缺血再灌注损伤保护作用的剂量相关性,以及不同剂量对血流动力学的影响,寻求产生最佳心肌保护作用和使患者心功能得到最佳恢复的剂量.方法 选择45例择期常规体外循环下行冠脉搭桥术患者,随机分成A、B、C三组.诱导后用微量注射泵持续输注异丙酚A组3 mg/(kg·h);B组5 mg/(kg·h);C组8 mg/(kg·h)直到手术结束.分别于体外循环前、主动脉开放后30min、6 h、24 h自桡动脉采血,测定血浆心肌肌钙蛋白Ⅰ(cTnI)浓度.分别测定开胸前、主动脉插管前、停体外循环、关胸前、关胸毕的平均动脉压(MAP)、外周血管阻力指数(SVRl)、心脏指数,同时观察主动脉开放后的心脏自动复跳情况.结果 三组从诱导至体外循环开始时间、体外循环时间、主动脉阻断时间、心肌保护方法以及心脏自动复跳情况无明显差异.三组患者cTnI水平于主动脉开放后迅速升高,主动脉开放后6小时处于高峰期.与A组比较,主动脉开放后B、C组患者cTnI值较低(P<0.01);B组与C组比较各时间点均无明显差异.三组患者停体外循环后心脏指数较开胸前升高明显(P<0.01),SVRI在停体外循环后均有下降(P<0.01),其中C组SVRI下降较其它两组显著,C组停体外循环后各时闻点心脏指数值较B组要低(P<0.05).结论 在冠脉搭桥术中,异丙酚以5 mg/(kg·h)持续输注至术毕,能减轻体外循环中心肌缺血再灌注损伤,血浆cTnI水平较低,有较高的心脏指数和满意的SVRI,能维持较为理想的血流动力学.     

七氟醚缺血再灌注早期处理对体外循环中肺内激活中性粒细胞作用的研究

目的研究体外循环心脏手术中七氟醚缺血及再灌注早期处理对肺内激活中性粒细胞的作用。方法 40例二尖瓣或者主动脉瓣膜置换的患者随机分为七氟醚组和对照组,每组20例。七氟醚组患者在阻断升主动脉前吸入2%七氟醚15 min,阻断后经膜式氧合器吸入2%七氟醚15 min,主动脉开放前经膜式氧合器吸入2%七氟醚15 min,开放后恢复机械通气继续吸入2%七氟醚15 min;对照组整个过程不给予任何吸入性麻醉药物。分别于体外循环前(T1)及主动脉开放后30 min(T2)抽取左右心房血样检测中性粒细胞计数和中心粒细胞表面CD11b的表达。分别于切皮前(T0)、体外循环前(T1)、主动脉开放后30 min(T2)、开放后2 h(T3)、开放后6 h(T4)、开放后24 h(T5)取桡动脉血检测动脉血气计算肺泡动脉血氧分压差P(A-a)O_2、氧合指数(OI)、观察不同时间点肺功能变化。结果与T1时间点比较,2组患者在T2时间点中性粒细胞计数、CD11b水平及其跨肺前后的差值都明显升高(P<0.05)。与对照组相比,在T2时间点七氟醚组白细胞计数、CD11b水平及其跨肺前后的差值均明显降低(P<0.05)。与T0时间点比较,2组患者在T2、T3、T4、T5时间点P(A-a)O_2均明显升高(P<0.05),而OI明显降低(P<0.05)。与对照组相比,在T2、T3、T4、T5时点七氟醚组P(A-a)O_2明显低于对照组(P<0.05),而OI明显高于对照组(P<0.05)。结论体外循环心脏手术中应用七氟醚缺血和再灌注早期处理可以抑制白细胞的激活、黏附,改善患者的肺功能,值得临床推广应用。     

BQ123对体外循环缺血再灌注心肌胰岛素抵抗干预作用的实验研究

目的:探讨内皮素受体拮抗剂BQ123对体外循环缺血再灌注心肌胰岛素抵抗(IR)的干预作用。方法:将18条杂种犬分为3组(n=6),Ⅰ组主动脉阻断30min,Ⅱ组主动脉阻断120min,Ⅲ组主动脉阻断120min且心脏停博液中加入BQ123。分别于体外循环转流前、主动脉开放后第15、45、75min4个时点,采集动脉、冠状静脉窦血液标本并进行右房心肌活检,测定各相关指标。结果:与Ⅱ组比较,Ⅲ组的动脉血糖、胰岛素、IR指数、应急激素、血浆内皮素-1及血浆肿瘤坏死因子-α水平升高幅度较小,心肌对葡萄糖的摄取和利用提前至再灌注45min,恢复至正常值更快(P<0.05或P<0.01)。结论:BQ123可以减轻体外循环缺血再灌注过程中的心肌IR,对其引起的损伤具有保护作用。     

促炎因子与抗炎因子在冠脉搭桥术围手术期的变化

目的:观察比较体外循环冠状动脉搭桥术(CABG)和非体外循环冠状动脉搭桥术(OPCAB)后炎症因子表达水平。方法:选取单纯冠脉搭桥手术患者57例。液相蛋白芯片系统(Liquichip)方法检测术前,术后1、4、24及72h的血浆中IL-6、IL-8、IL-10及TNF-α的表达水平,记录患者术后临床资料。结果:CABG组和OPCAB组术后炎症因子水平差异无统计学意义(均P>0.05)。2组术后IL-6、IL-8、IL-10水平均较术前有明显升高,术后1h达高峰(P<0.05),术后72h水平仍高于术前(P<0.05)。TNF-α水平术前术后差异无统计学意义(P>0.05)。结论:2组患者术后炎症因子水平与术前相比有明显的升高;CABG和OPCAB术后炎症因子水平差异无统计学意义。     

Effect of Cardiopulmonary Bypass on Gut Mucosal Barrier Function in Patients Undergoing Cardiac-Valve Replacement

目的:探讨围体外循环期瓣膜置换术患者肠黏膜屏障功能的变化及可能机制.方法:选择体外循环(CPB)心脏瓣膜置换术患者20例,按时点采取中心静脉血标本测定血清肠型脂肪酸结合蛋白(I-FABP)、白细胞介素(IL)-6、IL-10及D-乳酸水平,同时行静脉血气分析和血糖监测.结果:与CPB前比较,主动脉开放10 min时,血清D-乳酸和I-FABP值即显著升高;术后2h血浆D-乳酸达峰值,I-FABP维持较高水平;术后6h血浆I-FABP达峰值;术后18h血清D-乳酸和I-FABP值仍高于基础值.术后6h血浆I-FABP峰值与血糖和乳酸峰值呈正相关.结论:围CPB期肠黏膜屏障功能受损.神经-内分泌-免疫系统共同参与的应激反应与肠黏膜屏障功能损伤有关.     

体外循环对瓣膜置换术患者肠黏膜屏障功能的影响

目的:探讨围体外循环期瓣膜置换术患者肠黏膜屏障功能的变化及可能机制。方法:选择体外循环(CPB)心脏瓣膜置换术患者20例,按时点采取中心静脉血标本测定血清肠型脂肪酸结合蛋白(I-FABP)、白细胞介素(IL)-6、IL-10及D-乳酸水平,同时行静脉血气分析和血糖监测。结果:与CPB前比较,主动脉开放10min时,血清D-乳酸和I-FABP值即显著升高;术后2h血浆D-乳酸达峰值,I-FABP维持较高水平;术后6h血浆I-FABP达峰值;术后18h血清D-乳酸和I-FABP值仍高于基础值。术后6h血浆I-FABP峰值与血糖和乳酸峰值呈正相关。结论:围CPB期肠黏膜屏障功能受损。神经-内分泌-免疫系统共同参与的应激反应与肠黏膜屏障功能损伤有关。     

浅低温心脏不停跳心内直视手术对心肌酶学和超微结构的影响

目的 探讨浅低温不停跳心内直视手术对心肌保护的效果。方法20例单纯房间隔缺损或室间隔缺损患随机分成两组，其中浅低温不停跳组(Ⅰ组)12例、低温停跳组(Ⅱ组)8例。两组均切开右心房置入冠状静脉窦(CS)灌注管，不停跳组分别于体外循环(CPB)前(T1)、CPBl5min(T2)、CPB停止时(T3)及停止后15min(T4)取冠脉血和右心房心肌，停跳组分别于转流前(T1)、主动脉阻断时(T2)、主动脉开放时(T3)、主动脉开放后15min(T1)取冠脉血和右心房心肌。测定冠状静脉血中超氧化物歧化酶(SOD)、肌酸激酶(CK)、乳酸脱氢酶(LDH)的活性和丙二醛(MDA)的含量，测定心肌组织匀浆中钙-ATP酶(Ca2^ -ATPase)、一氧化氮合酶(NOS)的活性，观察两组心房肌超微结构的变化。结果体外循环开始后各时段两组LDH、CK均呈上升趋势，停跳组明显高于不停跳组。体外循环开始后停跳组SOD明显低于不停跳组而MDA明显高于不停跳组。停跳组心肌组织Ca^2 -ATPase、NOS活性较不停跳组低。结论与传统的冷停跳心脏手术相比浅低温不停跳手术具有很好的心肌保护作用。     

心脏搭桥术（非体外循环和体外循环下）术前术后细胞因子变化研究进展

心脏搭桥手术有体外和非体外循环下心脏搭桥手术两种,是临床常用的治疗手段。在心脏搭桥术术前术后其细胞因子及炎症因子的变化对心脏搭桥术的影响也极为重要,本文特对心脏搭桥术术前术后细胞因子及炎症因子的变化进行以下综述。     

异丙酚和异氟醚对非体外循环搭桥术患者围术期细胞因子的影响

目的:研究异丙酚和异氟醚对非体外循环搭桥术患者围术期炎性与抗炎性细胞因子平衡的影响。方法:择期非体外循环搭桥患者50例,随机分为2组。异丙酚组微量泵输入剂量为4～6mg·kg-·1h-1,异氟醚组吸入浓度为1%～1.5%。检测诱导前、打开心包、旁路血管开放30min,术后2h、24h血清白细胞介素6(IL-6)、白细胞介素10(IL-10)和肿瘤坏死因子α(TNF-α)的浓度。结果:2组患者旁路血管开放后IL-6浓度较术前升高(P<0.01),术后2h达高峰;术后2h异氟醚组高于异丙酚组(P<0.05)。IL-10浓度变化趋势与IL-6相似,旁路血管开放后、术后2h和24h异丙酚组高于异氟醚组(P<0.05)。2组患者TNF-α水平均无显著变化。结论:异丙酚麻醉促进IL-10的产生,抑制IL-6的产生,控制术中应激反应异丙酚优于异氟醚。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.