温血停跳液对兔缺血心肌的保护作用

目的；探讨温血停跳液对心肌的保护作用。方法：将24只家兔随机分为3组：I组（n=8），温血停跳液组；Ⅱ组（n=8)，冷晶体停跳液组；Ⅲ组（n=8)，温晶体停跳液组。I组为实验组，Ⅱ、Ⅲ组为对照组。使心肌缺血120min。3组均在主动脉阻断时和开放前给予剂量相等的停跳液，随后每隔20min灌注一次冷晶体停跳液。主动脉开放1min，取标本测定冠状窦血中乳酸脱氢酶1（LDH1）、肌酸磷酸激酶－MB（CK－MB）、心肌线粒体谷氨酸脱氢酶（GLDH）及心肌含水量（MWC），并观察心肌超微结构改变及线粒体立体学定量分析。结果：主动脉开放1min，冠状窦血中LDH1三组间无显性差别（P＞0．05）；GLDH，I 显高于Ⅱ、Ⅲ组（P＜0．05），Ⅱ、Ⅲ组间无显性差别（P＞0．05）；CK－MB，I组显低于Ⅱ、Ⅲ组（P＜0．05），Ⅱ、Ⅲ组间无显性差别（P＞0．05）；心肌含水量，I组显低于Ⅱ、Ⅲ组（P＜0．05），Ⅱ、Ⅲ组间无显性差别（P＞0．05）。心肌超微结构，I组分别低于Ⅱ、Ⅲ组（P＜0．05，P＜0．01），Ⅱ组低于Ⅲ组（P＜0．05）。结论：在主动脉阻断时和开放前应用温血停跳液，可取得比单纯给予晶体停跳液更好的心肌保护效果。     

三种心脏停跳液对心肌保护的对比研究

为评估三种心脏停跳液的心肌保护作用,将30例风湿性心脏病二尖辦病变随机分为温血停跳液组(温血组)、冷血停跳液组(冷血组)及冷晶体停跳液组(冷晶体液组),每组10例,观察心肌缺血30～50min期间血浆心肌肌钙蛋白T(cTn-T)、内皮素(ET-1)、心钠素(ANP)和心肌超微结构改变。结果表明:①温血组cTn-T在12h出现高峰;冷血组在12h出现高峰,随后的12h内有一平台期;冷晶体液组峰值出现在48h,体外循环后较前二组增高明显;②温血组ET-1在主动脉开放后下降速度最快,并且低于其它二组,其中冷晶体液组含量最高;③温血组在主动脉阻断后15min,ANP含量上升,恢复至正常水平时间最短;冷血组与冷晶体液组ANP在主动脉阻断后迅速下降,主动脉开放后上升并持续至1h;④心脏复跳后3组心肌超微结构均存在不同程度的损伤表现,以冷晶体液组最重,温血组最轻。结论:温血停跳液的心肌保护作用优于冷血停跳液和冷晶体停跳液。     

温血诱导心脏停搏及间断灌注在成人心内直视手术中的应用

目的 探讨温血诱导心脏停搏及间断温血灌注技术在成人心内直视手术中对心肌的保护作用。方法 将60例成人患者随机分成2组：温血诱导停搏及温血间断灌注组（实验组）;冷晶体诱导停搏及冷晶体间断灌注组（对照组）;2组主动脉阻断时间无明显差异。体外循环前、后60例患者分别抽血测定乳酸脱氢酶（LDH）,磷酸肌酸激酶（CK),电子显微镜观察缺血后心肌超微结构变化。结果 发现冷晶体组LDH、CK值均高于温血灌注组,显微镜观察缺血后心肌超微结构温血组优于冷晶体组。结论 温血诱导心脏停搏及间断灌注技术对成人心肌作用较为明显。     

温血心停跳液续灌与冷晶体间灌临床研究

目的 探讨温血心停跳液和冷晶体心停跳液对心肌的保护作用。方法 选择主动脉阻断时间大于60min的心脏手术20例。分别应用温血心停跳液持续灌注（Warmblood Continuous cardioplegia WBCC）（10例）和冷晶体心停跳液间断灌注（Coldcrystalloid intermittent cardioplegia CCIC）（IC例）的结果进行分析。,记录术前、术后6、12、24、48、72h血浆CPK、CK—MB、LDH、LDH．变化。结果两组在心脏直视手术中心脏停跳良好。围术期血液动力学指标、平均动脉压、中心静脉压、心率无明显差异。WBCC的血浆CPK、CK-MB、LDH、LDH1的水平均明显低于CCIC组（P〈0．05）。酶的释出量大为减少,并于72h内降至正常。恢复比CCIC组早。结论 WBCC能保护心脏停跳过程中有氧代谢的进行,减轻再灌注损伤,心肌酶释放减少。WBCC心肌保护效果优于CCIC。     

冷温血停搏液联合灌注在儿童先天性心脏病中的应用研究

目的 评价冷温血停搏液联合灌注在儿童先天性心脏病(CHD)手术中对心肌的保护作用,探讨更有效的心肌保护方法。方法 将24例儿童先天性心脏病病人随机分为两组:温血组(A组,n=12),采用温血诱导心脏停搏、冷血维持与终末温血灌注进行心肌保护;冷血组(B组,n=12),采用冷氧合血停搏液进行心肌保护。两组间主动脉阻断时间无明显差异;体外循环前(T1)、主动脉开放1h(T2)、主动脉开放6h(T3)、主动脉开放12h(T4)、主动脉开放24h(T5)分别抽血测定乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK—MB)、心肌肌钙蛋白T(cTnT)。结果 体外循环前两组间含量无差异。主动脉开放后LDH、CK—MB、cTnT含量较体外循环前明显升高(P<0.01),T4、T5时点B组,LDH、CK—MB含量较A组明显升高(P<0.05),T3～T5时点B组cTnT含量较A组明显升高(P<0.05)。结论 冷温血停搏液联合灌注对儿童先天性心脏病病人的心肌保护作用优于冷血心脏停搏液。     

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。     

氧合血与冷晶体心肌停搏液保护心肌的临床研究

目的：比较氧合血心肌停搏液与冷晶体心肌停搏液对心肌的保护效果。方法：心脏瓣膜直视术病人120例，随机分为氧合血心肌停博液组（I组）、冷晶体心肌停博液组（Ⅱ组）各60例。I组采用4：1高钾冷血停搏液（4℃-8℃）灌注诱导心肌停跳，术中每隔20min用4：1高钾冷血停搏液维持，在开放升主动脉钳之前用温血灌注。Ⅱ组采用4℃冷晶体心肌停搏液灌注，术中每20min复灌1次。结果：I组心脏自动复跳率明显高于Ⅱ组（P＜0．001）；术后低心排综合征和室性心律失常的发生率明显低于Ⅱ组（P＜0．01）；术后应用心肌正性肌力药物量及时间明显少于Ⅱ组（P＜0．05）。结论：氧合血心肌停博液较冷晶体心肌停搏液具有更好的保护心肌效果。     

体外循环三种灌注方式对心肌酶的影响

目的 :比较体外循环 (CPB)晶体冷停跳液灌注、不停跳转流方式灌注和氧合血与晶体冷停跳液 (4 :1)混合灌注3种方式对临床和心肌酶的影响。方法 :ASAⅠ～Ⅱ级病例41例。分组 :A组17例为晶体冷停跳液灌注 ;B组12例为不停跳转流方式灌注 ;C组12例为氧合血与晶体冷停跳液混合灌注。麻醉诱导药为安定、氟哌啶醇、芬太尼、丙泊酚和维库溴胺 ;维持药为芬太尼和维库溴胺。各组均在术前、术后和术后36小时抽血1次查谷草转氨酶 (AST)、肌酸激酶 (CK)、乳酸脱氢酶 (LDH)、α -羟丁酸脱氢酶(HBDH)、肌酸激酶同功酶 (CK -MB) ,检测值进行比较。结果 :心肌酶术毕之间比较 ,AST、LDH和HBDH3项A组均高于B组和C组 ,(P<0 01) ;CK和CK—MB2项A组高于C组 ,(P<0 01) ;CK—MB1项B组均高于A组和C组 ,(P<0 01)。术后36小时之间比较 ,AST、CK、LDH和HBDH4项B组均高于A组和C组 ,(P<0 01) ;CK—MB1项A组高于C组 ,(P<0 01)。结论 :氧合血与晶体冷停跳液 (4 :1)混合灌注优于晶体冷停跳液灌注和不停跳转流方式灌注 ,而晶体冷停跳液灌注又优于不停跳转流方式灌注     

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.     

温血逆行灌注对瓣膜置换同期冠脉搭桥术患者心肌保护作用的研究

目的：探讨使用温血逆行灌注技术对瓣膜置换同期冠脉搭桥术患者的心肌保护作用。方法40例行瓣膜置换手术加冠状动脉搭桥手术患者随机分为两组：研究组（温血逆行灌注组）和对照组（常规灌注组）,各20例。对照组常规冷晶体氧合血顺行灌注,研究组在温晶体氧合血的基础上给于逆行灌注。观察两组术中心脏复苏情况,分别于转流前、主动脉开放后10min、术后2h、术后4h和24h,采集动脉血标本,检查心肌肌钙蛋白T(cTnT)、心肌肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)。结果转流前及主动脉阻断开放后10min,两组心肌酶学指标无明显差别(P>0.05)。而术后2h、4h和24h研究组cTnT、CK和CK-MB指标低于对照组(P<0.05);且两组分别与转流前相比差异均有统计学意义(P<0.05)。结论温血逆行灌注对瓣膜置换同期冠状动脉搭桥手术患者有较好的心肌保护作用。     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.     

Trichinellosis in immigrants in Switzerland

We describe a case of trichinellosis diagnosed at the Division of Infectious Diseases, Hospital of Lugano, in January 2009. This case was associated with a cluster of cases and was traced to the consumption of contaminated meat after a wild boar hunt in Bosnia.