磷酸肌酸温血心停搏液终末灌注对心肌保护作用的临床研究

目的研究外源性磷酸肌酸（CP）对风湿性心脏病心瓣膜替换术患者在体外循环期间心肌再灌注损伤的保护作用。方法将46例风湿性心脏病体外循环心瓣膜替换术患者随机分为治疗组和对照组各23例。治疗组在开放主动脉前30min，在圣·托马斯（STH2）液中加入外源性磷酸肌酸终末温血半钾灌注，对照组应用常规圣·托马斯液。分别测定所有患者术前、主动脉开放2h、6h、24h、48h各时点中心静脉血中的红细胞压积（HCT）、乳酸脱氢酶（LDH）、磷酸肌酸激酶（CK）、磷酸肌酸激酶同工酶（CK-MB）及心脏肌钙蛋白T（cTnT）。记录术毕心脏自动复跳率和术后多巴胺用量。结果治疗组术后多巴胺用量明显少于对照组（P〈0．01）；术后6h、24h、48h的LDH、CK、CK-MB及cTnT水平均明显低于对照组（P〈0．01）；治疗组患者术毕心脏自动复跳率明显高于对照组。结论磷酸肌酸加入心停搏液中能显著提高心肌保护作用。     

前列地尔含血停搏液在体外循环中的心肌保护作用

目的 探讨心脏含血停搏液加入前列地尔脂微球制剂(Lipo-PGE1)在心肺转流(CPB)心内直视术中的心肌保护作用.方法 32例心脏瓣膜置换术患者随机分为两组(每组16例).B组在心脏含血停搏液中加入Lipo-PGE1 0.5 μg/kg;A组单用心脏含血停搏液作为对照.两组分别于CPB前(T0)和主动脉开放后2(T1)、6(T2)、16(T3)h采集桡动脉血,测定血清肌酸激酶同功酶(CK-MB)、肌钙蛋白Ⅰ(cTnI);观察心脏停跳及复跳情况、术后机械通气时间及术后正性肌力药物的应用情况.结果 两组术后CK-MB、cTnI较术前显著升高(P<0.05);与A组相比,B组术后多巴胺用昔显著减少(P<0.05),T2时的CK-MB及T2、T3时的cTnI显著降低(P<0.05).结论 Lipo-PGEl加入心停搏液中能显著提高心肌保护的效果.     

不同心肌保护方法在双瓣膜置换术中对心肌的保护作用

目的探讨双瓣膜置换术(DVR)中更有效的心肌保护措施。方法选择2010年2月～2011年8月在我院行二尖瓣和主动脉瓣双瓣膜置换术的30例患者为研究对象,根据入院顺序将患者分为3组,每组10例。①顺行灌注组:经左、右冠状动脉开口顺行性灌注冷血心脏停搏液,完成双瓣膜置换术;②逆行灌注组:经冠状静脉窦间断逆行灌注冷血心脏停搏液,完成双瓣膜置换术;③顺逆联合灌注组:先按顺行灌注方法,再采用逆行灌注方法,完成双瓣膜置换术;观察3组术后早期临床疗效;观察心肌乳酸释放率、血清心肌肌钙蛋白Ⅰ(cTnI)、磷酸肌酸激酶同工酶(CK-MB)的含量变化。结果 30例患者无手术死亡,均痊愈出院。顺行灌注组和顺逆联合灌注组主动脉阻断60min时心肌乳酸浓度低于逆行灌注组。主动脉开放20min、术后第1d顺行灌注组和顺逆联合灌注组的血清CK-MB、cTnI浓度低于逆行灌注组。结论以上3种心肌保护方法均有效,但顺行灌注组和顺逆联合灌注组效果较好;顺逆联合灌注方法操作方便,不影响手术进程,是一种有效的选择。     

腺苷后处理在心肺转流中的心肌保护作用

目的 观察腺苷药理性后处理在心肺转流心脏直视术中对心肌的保护作用.方法 45例心脏瓣膜置换术患者随机分为三组:腺苷预适应组转流前微量泵入腺苷;腺苷后处理组心脏灌停后术中再灌注时将腺苷加入停搏液中灌入或主动脉开放时由主动脉插管灌入;对照组在灌注液中加入同体积的生理盐水.三组分别于转流前、主动脉开放后2、6、16h采集患者桡动脉血,测血清肌酸激酶同功酶(CK-MB)、肌钙蛋白I(cTnI)、丙二醛(MDA);观察术后机械通气时间及术后正性肌力药物的应用.结果 腺苷预适应和后处理组术后多巴胺用量少,腺苷预适应组开放后2h CK-MB、6h MDA、开放后cTnI较对照组显著降低,后处理组开放后2、6h CK-MB、开放后MDA、cTnI均较对照组显著降低;预适应组和后处理组之间无显著差异(P>0.05).结论 外源性腺苷后处理和预适应在心肺转流中同样有显著的心肌保护作用.     

磷酸肌酸钠停搏液对心功能不全瓣膜病患者的心肌保护作用

目的:探讨磷酸肌酸钠(CP)对心功能不全瓣膜病患者术后心肌保护作用.方法:将82例择期行瓣膜置换术或成形术的慢性心功能不全患者随机分为两组:(1)对照组,常规使用4∶1含血心脏停搏液;(2)外源性磷酸肌酸钠组(CP组),在心脏停搏液中加入注射用磷酸肌酸钠.于转机前及术后24 h分别采血测定心肌酶谱,记录术后血管活性药物使用及机械通气等情况.结果:CP组的心肌酶谱各指标均显著低于对照组(P＜0.05);心脏自动复跳率明显高于对照组(P＜0.05);机械通气时间也较对照组缩短(P＜0.05);血管活性药物应用量均较对照组小(P＜0.05).结论:心脏停搏液中加入磷酸肌酸钠有明显的心肌保护作用,有利于心功能不全瓣膜病患者术后心功能恢复.     

体外循环心内手术主动脉开放前纯温血灌注的心肌保护效果

目的 探讨纯机器氧合血灌注诱复的心肌保护效果.方法 40例重症心脏瓣膜置换术患存均分两组,A组开放主动脉前用温血停搏液灌注+纯机器氧合血顺-逆灌注,待心脏复苏后再开放升主动脉;B组开放升主动脉前单用温血停搏液灌注后即开放升主动脉.于转流前、术毕、术后6 h和1、3、5 d取外周血测定心肌肌钙蛋白I(cTnI),记录心脏复跳、主动脉阻断、辅助循环、机械通气和ICU停留时间.结果 两组术后cTnI均较转流前增高,A组增高明显少于B组(P<0.01);A组自动复跳率高于B组,辅助循环、机械通气和ICU停留时间均短于B组(P<0.05).结论 主动脉开放前纯温血顺-逆灌注诱复后再开放方法有较好的心肌保护作用.     

自体冷血心脏停搏液对未成熟心肌CK-MB、cTnI及细胞线粒体的影响

目的通过对比自体冷血心脏停搏液与HTK液对未成熟心肌释放CK-MB、cTnI及细胞线粒体的影响,提示自体冷血心脏停搏液对未成熟心肌细胞的保护作用。方法年龄≤1岁行体外循环室间隔缺损修补术的患儿40例随机分为两组,实验组20例、对照组20例。主动脉阻断后,分别用自体冷血停搏液、HTK液根部灌注。于心脏停跳前、复跳后30min取右心耳标本1mm×1mm×1mm电镜观察细胞线粒体形态,并用Flameng法评价线粒体损伤程度。另外于术前、术毕、术后24、48h经桡动脉采血检测cTnI及CK-MB。研究上述两组各项指标的差异,运用统计学t检验的方法,得出研究结果。结果术后cTnI和CK-MB均明显升高,其中对照组cTnI和CK-MB升高较多(P<0.01)。主动脉阻断前心肌线粒体基本完好,偶见基质颗粒丢失或线粒体肿胀。主动脉开放后,线粒体出现不同程度损伤样改变,如颗粒丢失或嵴断裂。主动脉开放后两组患儿心肌线粒体Flameng评分显著增高(P<0.01),开放后对照组评分比自体冷血停搏液组明显增高(P<0.05)。结论自体冷血停搏液可减少未成熟心肌释放CK-MB与cTnI。能减轻缺血再灌注对未成熟心肌细胞线粒体的损伤。自体冷血心脏停搏液对未成熟心肌的心肌保护效果明显优于HTK液。     

Del Nido液联合磷酸肌酸钠在成人心脏瓣膜术中的应用效果分析

目的 评价Del Nido液联合磷酸肌酸钠在成人心脏瓣膜术中的临床应用效果。方法 60例行成人心脏瓣膜术患者,按照术中使用心肌保护液不同分为D组和T组,每组30例。D组顺灌Del Nido液+磷酸肌酸钠, T组顺灌St.Thomas液+磷酸肌酸钠,两组患者均在心脏停跳心内直视下行瓣膜手术。比较两组患者术中相关指标(升主动脉阻断时间、灌注量、灌注次数、自动复跳率、术后并发症发生率、围术期死亡情况)以及手术前后血浆肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)。结果 D组患者升主动脉阻断时间(106.90±29.47)min短于对照组的(123.83±35.45)min,灌注量(1257.33±370.93)ml、灌注次数(1.63±0.67)次少于T组的(2630.00±873.25)ml、(3.77±1.14)次,有统计学差异(P<0.05);两组患者自动复跳率、术后并发症发生率及围术期死亡率比较无统计学差异(P>0.05)。两组患者术后即刻cTnI水平均有明显上升,术后48 h明显出现下降,组内比较有统计学差异(P<0.05),但组间无统计学差异(P>0...     

间断冷含血停跳液在心脏瓣膜置换术中的心肌保护作用

目的评价间断冷含血停跳液在心脏瓣膜置换术中心肌保护的临床效果。方法54例心瓣膜置换术的患者,均使用按4:1比例灌注冷含血停跳液,观察体外循环时间、主动脉阻断时间、自动复跳率、住院死亡率。结果体外循环时间47～218mins,阻断主动脉时间26～102mins,心脏自动复跳43例,占80%,住院死亡2例,死亡率3.7%。结论间断冷含血停跳液在心瓣膜置换术中有良好的心肌保护作用。     

磷酸肌酸钠停搏液对未成熟心肌保护效果的临床观察

目的 探讨磷酸肌酸钠(cP)停搏液在婴幼儿心内直视术中的心肌保护效果.方法 选择60例择期在体外循环(ECC)和心脏停搏下,行法洛四联症(TDF)根治术的先天性心脏病(先心病)患儿,随机分为试验组和对照组.主动脉阻断后于其根部插针顺行灌注4℃停搏液,试验组灌注CP停搏液(在单纯冷晶体高钾停搏液中加入CP,浓度为10 mmol/L),对照组灌注单纯冷晶体高钾停搏液.2组患儿分别于ECC前、主动脉阻断(ACC)30 min后,术后2、24、48 h抽取中心静脉血,测血清心肌酶(CK-MB、cTnI)的浓度;分别记录,临床观察指标(心脏诱导停搏时间,自动复跳时间,自动复跳率,术后呼吸机维持时间、ECC停止及术后24 h多巴胺、盐酸肾上腺素用量和使用率).结果 试验组在各临床观察指标上均优于对照组(P<0.05);2组的血清心肌酶均于ACC 30min后开始上升,并于术后24 h达高峰,与ECC前比较有统计意义(P<0.01).2组间比较,试验组在ACC 30 min后各时点升高的幅度明显低于对照组(P<0.05),差异有统计学意义(P<0.05).结论婴幼儿心内直视术中应用含CP的冷晶体停搏液对未成熟心肌具有良好的保护作用,优于单纯的冷晶体心脏停搏液.[关键词l磷酸肌酸钠;冷晶体停搏液;心内直视术;未成熟心肌;心肌保护     

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.

     

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.     

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.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.