异丙酚对内毒素诱导大鼠急性肺损伤的保护作用

目的 探讨不同剂量异丙酚对内毒素(LPS)诱导大鼠急性肺损伤(ALI)的保护作用。方法 股静脉注射内毒素(LPS)5mg/kg,建立大鼠ALI模型。24只健康雄性Wistar大鼠随机分为四组:对照组(C组,输注生理盐水),LPS对照组(L组,股静脉注射LPS后输注生理盐水),低剂量异丙酚治疗组(Lp1组,股静脉注射LPS后立即输注异丙酚5mg/kg,随后5mg·kg~(-1)·h~(-1)维持),高剂量异丙酚治疗组(Lp2组,股静脉注射LPS后立即输注异丙酚10mg/kg,随后10mg·kg~(-1)·h~(-1)维持),每组6只。于注射LPS后1、2、3、4h抽血并于4h时处死大鼠,酶联免疫吸附法(ELISA)测定血清和支气管肺泡灌洗液(BALF)中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)水平;测肺湿/干重比;并观察BALF中性粒细胞计数比、蛋白浓度。结果 L组大鼠肺湿/干重、BALF中性粒细胞计数比及蛋白浓度均明显增加(P<0.05),血清及BALF中TNF-α、IL-1β、IL-10水平显著性升高(P<0.01),而异丙酚治疗组的各项指标均较内毒素组减轻,大剂量作用更明显(P<0.01)。结论 异丙酚对内毒素诱导的大鼠急性肺损伤有保护作用,大剂量作用较明显。     

抗氧化剂对内毒素性休克大鼠α1-肾上腺素能受体mRNA表达的影响

目的评价抗氧化剂对内毒素性休克大鼠α1-肾上腺素能受体(α1-AR)mRNA表达的影响.方法雄性SD大鼠40只,随机分成5组(n=8)空白对照组(C组);内毒素休克组(LPS组,静脉注射LPS 15 mg·kg-1);异丙酚组(P组,注射LPS后1 h,静脉注射异丙酚10 mg·kg-1,继以10 mg·kg-1·h-1静脉持续泵注4 h);尿酸组(UA组,注射LPS后1 h,腹腔注射UA 200 mg·kg-1);N-乙酰5-甲氧基色胺组(MLT组,注射LPS后1 h,腹腔注射MLT 10 mg·kg-1).各组大鼠于注射LPS后6h处死,迅速取胸主动脉、下腔静脉、心脏、肝脏、肺脏、肾脏组织.提取各组织的总RNA,逆转录聚合酶链反应(RT-PCR)法检测各组织α1A-AR、α1B-AR和α1D-AR mRNA的表达.结果与C组比较,LPS组α1-AR三种亚型mRNA在胸主动脉、肝脏、肺脏、肾脏组织表达均下降(P＜0.05),α1A-AR、α1B-AR mRNA在下腔静脉、心脏组织表达均下降(P＜0.05).与LPS组比较,P组α1A-AR mRNA在肺脏和肾脏组织表达增加(P＜0.05),α1B-AR、α1D-AR mRNA在胸主动脉、肝脏、肺脏、肾脏组织表达增加(P＜0.05),α1B-AR mRNA在下腔静脉和心脏组织表达增加(P＜0.05);UA组α1A-AR mRNA在肾脏组织表达增加(P＜0.05),α1B-AR mRNA在肺脏以外各组织表达均增加(P＜0.05),α1D-AR mRNA在胸主动脉、肝脏、肺脏、肾脏组织表达增加(P＜0.05);但MLT组α1-AR三种亚型mRNA表达水平变化无统计学意义(P＞0.05).结论内毒素性休克大鼠α1-AR的基因表达普遍下调,抗氧化剂的抗休克作用机制与α1-AR基因表达上调有关.     

蛋白O-GlcNAc修饰在谷氨酰胺改善感染性休克大鼠血管低反应性中的作用

目的 评价蛋白O位-N-乙酰葡萄糖胺(O-GlcNAc)修饰在谷氨酰胺改善感染性休克大鼠血管低反应性中的作用.方法 健康雄性SD大鼠32只、2～3月龄,体重250 ～ 300 g,采用随机数字表法,将其随机分为4组(n=8):假手术组(S组)、感染性休克组(C组)、谷氨酰胺组(G组)和四氧嘧啶组(A组).采用盲肠结扎穿孔法制备感染性休克模型.于造模前1hG组和A组经30 min静脉输注谷氨酰胺0.75 g/kg,A组同时腹腔注射四氧嘧啶90 mg/kg.于造模后6h、依次静脉注射去氧肾上腺素(PE) 0.5、1,0、2.0、2.5 μg/kg,每次间隔20 min,计算给药后MAP的增幅百分比.经心内穿刺采集血样,测定血清NO浓度.处死后取胸主动脉环行血管张力实验,计算离体血管环对PE反应的半数有效浓度(EC50)和最大效应(Emax)；测定胸主动脉蛋白O-GlcNAc修饰和诱导型一氧化氮合酶(iNOS)水平.结果 与S组比较,C组、G组和A组MAP增幅百分比、离体血管环对PE反应的Emax降低,离体血管环对PE反应的EC50、血清NO浓度、胸主动脉iNOS含量和蛋白O-GlcNAc修饰水平升高(P＜0.05)；与C组比较,G组胸主动脉蛋 白O-GlcNAc修饰水平升高,离体血管环对PE反应的EC50降低,G组和A组MAP增幅百分比、离体血管环对PE反应的Emax升高,胸主动脉iNOS含量和血清NO浓度降低(P＜0.05)；与G组比较,A组高体血管环对PE反应的EC50、血清NO浓度、胸主动脉iNOS含量升高,MAP增幅百分比、离体血管环对PE反应的Emax和蛋白O-GlcNAc修饰水平降低(P＜0.05).结论 谷氨酰胺通过提高蛋白O-GlcNAc修饰水平改善感染性休克大鼠血管低反应性.     

cGMP依赖性蛋白激酶G抑制剂对内毒素孵育大鼠胸主动脉血管环反应性的影响

目的 评价特异性cGMP依赖性蛋白激酶G(PKG)抑制剂(D)-DT-2对内毒素(LPS)孵育大鼠胸主动脉血管环收缩功能的影响.方法 实验Ⅰ 取SD大鼠胸主动脉血管环,采用随机数字表法分为3组(n=5):KH液组、DT2组和DDT2组,用50 μmol/L 8-Br-cGMP孵育25 min后加入上述各药,比较各组血管环的张力变化.实验Ⅱ 将SD大鼠胸主动脉血管环,采用随机数字表法分为4组(n=5):对照组、LPS组、LPS-DT2组和LPS-DDT2组,在体外测定LPS孵育3h后各组血管环在苯肾上腺素(PE)作用下最大收缩力(Emax)以及产生最大收缩力的半数有效浓度(EC50).结果 实验ⅠPKG抑制剂DT-2和(D)-DT-2能够使8-Br-cGMP舒张的血管环收缩,DDT2组血管环的Emax明显高于DT2组(P＜0.05).实验ⅡDT-2和(D)-DT-2均可以显著提高LPS孵育血管环的收缩功能;与LPS组比较,LPS-DT2组和LPS-DDT2组Emax升高,EC50降低(P＜0.01).LPS-DDT2组与LPS-DT2组相比Emax升高,EC50降低(P＜0.05).结论 PKG抑制剂可提高内毒素孵育血管环的收缩功能,(D)-DT-2恢复血管反应性的作用强于DT-2.     

异丙酚早期给药对内毒素休克大鼠急性肺损伤的保护作用

目的观察不同时点给予异丙酚对脂多糖(LPS)致内毒素休克大鼠急性肺损伤(ALI)的保护作用及机制.方法静脉注射LPS 8 mg·kg-1复制内毒素致ALI模型,雄性Wistar大鼠76只随机分为5组对照组(A组,n=8)、LPS组(B组,n=17)、异丙酚给药组(C～E组,n=17),C组、D组和E组分别于LPS注入前1 h、LPS注入即刻、LPS注入后1 h、静脉注射异丙酚5 mg·kg-1,继以10mg·kg-1·h-1持续泵注.从注入LPS至实验结束,历时5 h.持续监测平均动脉压(MAP),测定支气管肺泡灌洗液(BALF)中蛋白(BALFpro)、一氧化氮(NO)、肿瘤坏死因子(TNF-α)、肺组织湿/干重比、肺通透指数(PPI)、肺组织中硝基酪氨酸(NT)表达、NT的Westem Blot、肺组织中诱生型一氧化氮合酶mRNA表达及大鼠死亡率.结果与基础值比较,B组、C组、D组、E组在注入LPS后3、5 h MAP降低(P＜0.05),与B组比较,C组、D组注入LPS后5 h MAP降低(P＜0.05).与A组比较,B组、D组、E组PPI、W/D、BALFpro及BALF中TNF-α、NO均升高(P＜0.01),C组W/D、BALFpro及BALF中TNF-α、NO升高(P＜0.01);与B组比较,C组、D组PPI、W/D、BALFpro及BALF中TNF-α、NO均降低(P＜0.05或0.01),E组W/D、BALFpro及BALF中NO降低(P＜0.05).与B组比较,A组NT微弱表达,B组表达明显增强,C组、D组、E组表达减弱,以C组最明显.与B组比较,C组、D组、E组吸光度比值降低(P＜0.01).A组、B组、C组、D组、E组大鼠死亡率分别为0%、64.7%、11.8%、23.5%和41.2%.结论异丙酚早期给药对内毒素致ALI有保护作用.     

氯胺酮对内毒素血症大鼠炎性反应及血液动力学的影响

目的观察不同剂量氯胺酮对内毒素血症大鼠炎性反应及血液动力学的影响。方法36只成年雄性Wistar大鼠随机分为6组,每组6只,A组(对照组):静脉输注生理盐水10ml·kg-1·h-1;B组:静脉注射内毒素(LPS)5mg·kg-1,1min后静脉输注生理盐水10ml·kg-1·h-1;C组:静脉注射LPS5mg·kg-1,1min后静脉输注氯胺酮0.5mg·kg-1·h-1;D组:静脉注射LPS5mg·kg-1,1min后静脉输注氯胺酮5mg·kg-1·h-1;E组:静脉注射LPS5mg·kg-1,1min后静脉输注氯胺酮50mg·kg-1·h-1;F组:静脉输注氯胺酮50mg·kg-1·h-1。记录注射LPS后30、60、90、120min时平均动脉压(MAP)和心率(HR),并于注射LPS后120min时放血处死大鼠,测定外周血单核细胞(PBMC)中NF-κB含量及血浆肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)浓度。结果与基础值比较,B组注射LPS后MAP下降,HR增快,PBMC中NF-κB含量增加,血浆TNF-α、IL-6浓度升高。与B组比较,E、F组.MAP在注射LPS后120min升高,E组HR在注射LPS后90、120min、F组HR在注射LPS后60-120min降低,C、D、E组PBMC中NF-κB含量及血浆TNF-α浓度降低(P<0.05或0.01),但血浆IL-6浓度差异无统计学意义(P>0.05)。结论50mg·kg-1·h-1氯胺酮改善内毒血症大鼠血液动力学的紊乱,又可以在一定程度上抑制炎性反应,0.5、5mg·kg-1     

异丙酚对内毒素血症鼠NO、SOD及MDA水平的影响

目的 研究异丙酚对内毒素血症大鼠体内一氧化氮(NO)、超氧化物歧化酶(SOD)、丙二醛(MDA)的影响。方法 72只Waster雄性大鼠随机分为三组,对照组(C组),内毒素组(L组)和异丙酚 内毒素组(P组)。L组腹腔内注入内毒素10mg·kg-1;P组皮下缓慢注入异丙酚20mg·kg-1·h-1后再注入内毒素10mg·kg-1;C组:腹腔内注入等量生理盐水。L组和P组在注射后30、90、180、360min取静脉血并处死动物(每时间点8只),C组在相应时间点留取3ml静脉血后,于360min处死大鼠留取肺组织。测定各时间点血清和肺组织中MDA和NO浓度及外周红细胞SOD活性。结果 P组用异丙酚后显著性降低内毒素血症大鼠血清和肺组织中NO和MDA浓度,并增加SOD活性,与L组比较差异有显著性(P<0.01或P<0.05)。结论 异丙酚可降低内毒素血症鼠NO水平,抑制MDA合成,增加SOD活性,具有一定的抗氧化作用,可改善内毒素血症鼠的功能状态。     

异丙酚早期给药对内毒素休克大鼠的保护效应

目的 观察不同时点给予异丙酚对内毒素休克大鼠的作用及机制。方法 静脉给予脂多糖(LPS)8 mg·kg~(-1) 复制内毒素休克模型,雄性 Wistar大鼠76只随机分5组:对照组(A组);LPS组(B组);C、D、E组为异丙酚+LPS组,分别于LPS注入前1h、LPS注入即刻、LPS注入后1h,均静注异丙酚5 mg·kg~(-1),继以10 mg·kg~(-1)·h~(-1)持续泵注。观察动物 MAP、PaO_2,pH,血清肿瘤坏死因子(TNF-α)、一氧化氮(NO)浓度,肺组织TNF-α及丙二醛(MDA)含量、髓过氧化物酶(MPO)活性的变化。并比较各组存活率。结果 与B组比较,C、D组可不同程度地逆转MAP、PaO_2 、pH的下降,抑制血清TNF-α、NO水平及肺组织TNF-α、MDA、MPO水平的升高,动物存活率提高(P<0.01或0.05)。E组上述指标改善较C组、D组弱。结论 异丙酚早期给药对内毒素休克起保护效应。     

体温对内毒素致急性肺损伤大鼠肺微血管通透性的影响

目的探讨亚低温和高温对内毒素致急性肺损伤(ALI)大鼠肺微血管通透性的影响。方法健康雄性SD大鼠48只,体重300～350 g,随机分为4组(n=12),常温对照组(A组)静脉注射37℃生理盐水;常温内毒素组(B组)静脉注射脂多糖(LPS)5 mg·kg-1;亚低温 内毒素组(C组)静脉注射LPS 5 mg·kg-1,维持直肠温31.5～32℃;高温 内毒素组(D组)静脉注射LPS 5 mg·kg-1,维持直肠温39.5～40℃。动脉血氧合指数(PaO2/FiO2)≤300 mm Hg即ALI模型制备成功。于ALI 6 h后处死大鼠,取肺组织,清洗固定后测定肺微血管通透性指标:肺湿/干重量比(W/D)、肺泡灌洗液(BALF)蛋白(BALFpro)、肺通透性指数(PPI)、肺微血管通透性指数(PMPI)及肺组织硝基酪氨酸(NT)、髓过氧化物酶(MPO)、丙二醛(MDA)含量,观察肺组织病理学改变。结果与A组比较,B组、C组、D组PPI、W/D、BALFpro、PMPI和肺组织MPO、MDA、NT均升高(P<0.05);与B组比较,C组上述指标降低,D组上述指标升高(P<0.05);与C组比较,D组PPI、W/D、BALFpro、PMPI和肺组织MPO、MDA、NT升高(P <0.05)。结论高温加重内毒素血症大鼠ALI程度,亚低温通过抑制ONOO-生成,抑制了肺微血管通透性的升高,可减轻大鼠内毒素致ALI。     

异丙酚对内毒素所致急性肺损伤大鼠肺组织TGF-β1/Smad2信号通路的影响

目的 探讨异丙酚对内毒素所致急性肺损伤大鼠肺组织转化生长因子(TGF)-β1/Smad2信号通路的影响.方法 健康雄性Wistar大鼠56只,7～8周龄,260 ～ 300 g,采用随机数字表法,将其随机分为5组:正常对照组(A组,n=8)、LPS组(B组,n=12)、异丙酚不同时点给药组(C组～E组,n=12).A组给予等容量生理盐水,B组静脉注射脂多糖8 mg/kg,C组、D组和E组分别于给予LPS前1h、给予LPS后即刻和给予LPS后1h时静脉注射异丙酚5 mg/kg,随后以10 mg· kg-1·h-1速率输注至给予LPS后5h.分别于给予LPS前即刻、给予LPS后1、3、5h时采集动脉血样,测定pH值和PaO2,随后处死大鼠,取肺组织,计算湿/干重比(W/D),测定肺组织TGF-β1 mRNA和Smad2表达.结果 与A组比较,B组和E组pH值和PaO2降低,肺组织W/D升高,TGF-β1 mRNA和Smad2表达上调(P＜0.05);与B组比较,C组和D组pH值和PaO2升高,肺组织W/D降低,TGF-β1 mRNA和Smad2表达下调,E组PaO2升高(P＜0.05).结论 异丙酚减轻内毒素所致ALI的机制与抑制TGF-β1/Smad2通路激活有关.     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.