泡状棘球蚴感染诱导免疫耐受的研究

目的 观察泡状棘球蚴感染对纯系大鼠异位移植心脏存活时间的影响并探讨发生机制.方法 建立Brwon norway(BN)大鼠到Lewis (LEW)大鼠的颈部异位心脏移植模型.对照组(n=12)以健康的LEW大鼠为受者;实验组(n=12)以感染泡状棘球蚴的LEW大鼠为受者.术后观察移植心的存活时间、组织病理学变化,测定血清内白细胞介素-4(IL-4)和y-干扰素(IFN-γ)水平.FACS 流式检测实验组和对照组大鼠脾内CD4+ CD25+调节性T细胞(CD4+ CD25+ Treg细胞)的数量水平.结果 实验组与对照组移植心的存活时间分别为(16.17±3.19)d及(7.92±1.93)d,两组差异有统计学意义(P＜0.05).实验组移植心的组织病理学分级(平均分级为3.38级)与对照组(平均分级为3.79级)比较,差异无统计学意义(P＞0.05).发生排斥反应后,实验组血清内IL-4水平为(152.21 ±45.62) ng/L高于对照组(50.85±22.15) ng/L,而实验组血清内IFN-γ水平为(12.35±1.02) ng/L水平低于对照组(42.63±4.15) ng/L,两组差异均有统计学意义(P ＜0.05);FACS流式检测结果提示实验组大鼠脾内CD4+ CD25+ Treg细胞数量为10.8％,高于对照组的6.1％,两组差异有统计学意义(P＜0.01).结论 泡状棘球蚴感染造成Th1/Th2向Th2类细胞因子偏移,通过介导CD4+ CD25+ Treg细胞数量增加而导致大鼠异位移植心脏存活时间延长,它可能是诱导移植免疫耐受的原因之一.     

针对OX40小于扰RNA供体转染抗大鼠肝移植排斥反应

目的 观察RNA干扰阻断OX40-OX40L共刺激通路对大鼠移植肝存活时间的影响.方法 制作DA大鼠到Lewis大鼠的原位肝脏移植模型,移植前取预先制备的5 ml含5×109pfu的pLVTHM-OX40-siRNA重组慢病毒,灌注感染移植供肝30 min,术后观察受者存活时间,移植肝脏进行组织病理学检查;采用ELISA法检测大鼠外周血IL-2,IFN-γ,的水平,并进行受者大鼠脾细胞对供者大鼠脾细胞的混合淋巴细胞反应(MLR).结果 转染组受者肝脏移植物的存活时间为(74.00±3.79)d,明显长于对照组和未转染组;转染组移植肝组织炎细胞侵润、间质水肿、肝组织坏死程度较对照组和未转染组减轻,实验组大鼠脾细胞刺激T淋巴细胞增殖的能力降低(P<0.01);移植术后的第7天,转染组血清IL-2浓度为(46.0±8.4)ng/L,IFN-γ浓度为(202.7±14.6)ng/L,均显著低于对照组和未转染组(P<0.05).结论 转染靶向OX40的siRNA,在体内可通过阻断OX40-OX40L共刺激通路,抑制大鼠肝脏移植后的排斥反应,延长大鼠移植肝的存活时间.     

转染IL-12p35siRNA的供者树突状细胞延长大鼠移植小肠的存活时间

目的探讨转染IL-12p35siRNA的供者树突状细胞(DC)对大鼠移植小肠存活时间的影响。方法在体外以IL-12p35siRNA转染Wistar大鼠骨髓来源的DC,用逆转录聚合酶链反应测定转染细胞IL-12p35mRNA的表达,进行混合淋巴细胞反应,观察DC对SD大鼠T淋巴细胞的刺激作用。制作Wistar大鼠到SD大鼠的节段小肠异位移植模型,转染组小肠移植前7 d经阴茎背静脉给受者注射转染IL-12p35siRNA的DC 4×106个/只;未转染组移植前7 d注射未转染的DC 4×106个/只;对照组注射生理盐水。术后观察受者的存活时间,移植小肠进行组织病理学检查,应用酶联免疫吸附试验检测受者血清中白细胞介素2(IL-2)和γ干扰素(IFN-γ)的水平。结果DC转染IL- 12p35siRNA后,IL-12p35mRNA的表达明显降低,其刺激T淋巴细胞增殖的能力降低(P<0.01)。转染组受者小肠移植后的存活时间为(16.63±3.38)d,明显长于对照组和未转染组(P<0.01);转染组移植小肠组织中仅有炎症细胞浸润、黏膜层肿胀,绒毛腺体结构和肌层破坏程度较对照组和未转染组明显减轻;术后第10天,转染组的血清IL-2浓度为(175.8±11.5)ng/L,IFN-γ浓度为(70.6±7.2)ng/L,均显著低于对照组和未转染组(P<0.05)。结论转染IL-12p35siRNA,在体外可减轻DC对T淋巴细胞的刺激作用,在体内可抑制大鼠小肠移植后的排斥反应,延长移植小肠的存活时间。     

供心体外转染腺病毒介导的CD40Ig融合基因延长小鼠移植心脏存活时间

目的探讨体外转染CD40Ig融合基因对小鼠移植心脏存活时间的影响。方法构建携带小鼠CD40胞外段和人IgGFc融合基因的重组腺病毒载体(AdCD40Ig),以BALB/c小鼠为供者,C57BL/6小鼠为受者,建立小鼠腹部异位心脏移植模型,实验组供心移植前在体外以AdCD40Ig灌注,转染CD40Ig基因,另设空载体转染对照组、非转染对照组和近交系对照组(供、受者均为近交系C57BL/6小鼠)。术后观察移植心的存活及移植物中炎症细胞浸润情况,采用酶联免疫吸附试验(ELISA)检测受者体内CD40Ig融合蛋白表达情况,流式细胞仪检测受者体内产生γ干扰素(IFN-γ)的脾细胞。结果实验组移植心的存活时间达(15.8±0.7)d,明显长于空载体转染对照组和非转染对照组(P<0.01)。术后第2d,实验组受者体内CD40Ig融合蛋白表达最高,1周后明显降低。术后第7d,实验组移植心组织中浸润的炎症细胞明显比未处理对照组和空载体对照组少。实验组产生IFN-γ的CD4+和CD8+T淋巴细胞分别为(2.18±0.16)%和(10.82±0.74)%,与近交系对照组接近,明显低于未处理对照组和空载体对照组(P<0.01)。结论供心体外转染CD40Ig融合基因可有效抑制移植后受者体内同种T淋巴细胞的增殖,并延长移植心的存活时间。     

大鼠供心转染CTLA4-Ig基因抑制心脏移植后排斥反应

目的研究大鼠供心转染CTLA4-Ig基因抑制心脏移植术后排斥反应的可行性。方法以BN大鼠为供者,Lewis大鼠为受者,建立心脏移植模型。将实验分为2组。对照组:供心获取过程中不给予任何干预处理;实验组:在供心获取的过程中,以质粒载体携带CTLA4-Ig(pUF1-CTLA4-Ig)经过冠状动脉灌注供心。采用逆转录聚合酶链反应(RT-PCR)检测供心组织中CTLA4-IgmRNA的表达,观察移植心存活时间;酶联免疫法(ELISA)检测血清γ-干扰素(IFN-γ)和白细胞介素-4(IL-4)水平;观察移植心的组织学改变;用免疫组织化学SABC法检测移植心组织中CD4 和CD8 T细胞的浸润。结果实验组移植心存活时间较对照组明显延长[(11.70±1.24)dvs(5.62±0.74)d,P<0.05]。移植后5d,实验组移植心组织中可见CTLA4-IgmRNA的表达;对照组病理学检查可见心肌间质出现弥漫性的炎性细胞浸润,伴有局部的心肌坏死,组织间质水肿,实验组仅有局灶性血管外周及心肌间质内炎性细胞浸润,未见坏死;对照组移植心组织中浸润的CD4 和CD8 T细胞数量明显高于实验组(P<0.01);实验组血清IFN-γ水平明显低于对照组(P<0.01),但血清IL-4水平差异无统计学意义(P>0.05)。结论经冠状动脉灌注转染CTLA4-Ig基因,可以抑制心脏移植后排斥反应。     

抗CD8单抗与抗CD40L单抗联合应用对小鼠心脏移植后慢性排斥反应的影响

目的 探讨干预慢性迟发性超敏反应（DTH）与CD8^＋T淋巴细胞的细胞毒等效应机制对同种小鼠心脏移植后慢性排斥反应的影响。方法 建立小鼠颈部异位心脏移植模型，实验组以BALB／c小鼠为供者，C57BL／6小鼠为受者，术后0、2、6及14d腹腔注射抗CD8单克隆抗体（抗CD8单抗）200μg／d，术后0、2及4d腹腔注射抗CD40L单克隆抗体（抗CD40L单抗）250μg／d；同系移植对照组供、受者均为BALB／C小鼠，术后同期腹腔注射等量生理盐水；同种移植对照组以BALWc小鼠为供者，C57BL／6小鼠为受者，术后不使用上述单抗。观察各组移植心的存活时间及移植心组织病理学变化。结果同种移植对照组移植心的平均存活时间为7．3d；实验组与同系移植对照组移植心的存活时间均超过60d。同种移植对照组移植心呈典型急性排斥反应病理学改变；同系移植对照组移植心组织未见明显病理变化；实验组移植心呈现血管周围炎、间质纤维化和血管内膜增生等慢性排斥反应组织病理改变。结论 清除CD8^＋T淋巴细胞和阻断CD40／CD40L通路的处理方案虽可预防急性排斥反应，显著延长移植心的存活时间，但并不能阻止慢性排斥反应的发生。     

大鼠肝移植后树突状细胞的迁移变化

目的：研究大鼠肝移植后树突状细胞（DC）的迁移情况。方法：制作Wistar大鼠到SD大鼠的肝移植模型（实验组），并设Wistar大鼠间肝移植作为对照（对照组）。分别于术后第3、5、7天处死受者，切取移植肝组织及腹腔淋巴结，进行组织学观察，并以免疫组织化学染色观察移植肝组织和淋巴结中S-100^＋DC的动态变化，以及CD25^＋T淋巴细胞在淋巴结的活化增殖。结果：肝组织病理学检查显示，实验组移植后第5天即出现轻至中度急性排斥反应，至第7天发展成中至重度排斥反应，受者存活时间（9．7±1．4）d。免疫组织化学染色显示，术后第3天实验组移植肝组织中DC数量明显增多，于第5天达到高峰，第7天则出现下降，明显高于对照组，差异有统计学意义（P〈0．05）。从第3天开始，淋巴结中DC数量明显增多，第5、7天持续上升，与对照组相比，差异有统计学意义（P〈0．05）。移植术后第3天，实验组淋巴结中CD25^＋T淋巴细胞明显增多，呈现明显的T淋巴细胞活化增殖反应。结论：同种异体肝移植后，DC对抗原的摄取和递呈加速，产生对T淋巴细胞强烈而持久的刺激，最终激活T淋巴细胞，导致排斥反应的发生。     

腹腔注射姜黄素延长小鼠移植心脏存活时间的作用及其机制

目的 探讨腹腔注射姜黄素对小鼠移植心脏存活时间的影响及其机制.方法 选择C57BL/6和Babl/c小鼠各30只,分别作为心脏移植的供、受者,进行小鼠腹部心脏移植.随机将受者分为对照组、小剂量组和大剂量组,在术前1 d至术后7 d每天分别给受者腹腔注射生理盐水、5 μg/μl和10 μg/μl的姜黄素溶液,注射量均为20μl/g.术后观察各组移植心脏存活时间;术后第7天,每组分别取3只受者的移植心脏行病理学检查,观察排斥反应情况.并采用酶联免疫吸附试验(ELISA)法检测受者血清白细胞介素2(IL-2)、IL-4、IL-10及γ干扰素(IFN-γ)的水平,采用混合淋巴细胞反应检测受者T淋巴细胞对供者抗原的反应性,分别采用免疫印迹法和ELISA法检测受者T淋巴细胞核因子κB(NF-κB)p65核转位和NF-κB p65 DNA的结合活性.结果 对照组、小剂量组和大剂量组移植心存活时间分别为(8.0±3.3)d、(17.0±2.4)d和(23.0±2.2)d,三组间的差异均有统计学意义(P＜0.01).术后第7天,对照组、小剂量组和大剂量组移植心排斥反应分级分别为Ⅱ～Ⅲ、Ⅰ～Ⅱ和0～Ⅰ级.对照组、小剂量组和大剂量组血清IL-2和IFN-γ的水平依次降低,而血清IL-4和IL-10的水平依次增高,三组间各细胞因子的差异均有统计学意义(P＜0.01).小剂昔组和大剂量组的T淋巴细胞经供者T淋巴细胞刺激后,其增殖能力减弱,大剂量组尤其明显.小剂量组和大剂量组的T淋巴细胞NF-κB p65核转位减少,NF-κB 065 DNA的结合活性降低.大剂量组的该效应明显强于小剂量组(P＜0.01).结论 姜黄素能显著延长小鼠移植心脏存活时间,抑制心脏移植排斥反应,其机制可能是姜黄素能够抑制TH1型细胞和促进TH2型细胞因子的表达,使受者对供者抗原处于免疫低反应状态.     

他克莫司处理的供者树突状细胞延长大鼠移植心脏的存活时间

目的 研究经他克莫司(Tac)处理的供者未成熟树突状细胞(imEX3)在延长大鼠移植心脏存活时间中的作用和机制.方法 以Wistar大鼠为供者,SD大鼠为受者,行颈部异位心脏移植.心脏移植前将受者随机分为3组,每组15只,进行不同的预处理.第1组:为对照组,术前7 d经受者的尾静脉注射生理盐水1.0ml;第2组:为未经Tac处理组,术前7 d经受者的尾静脉注射未经Tac处理的imDC 2×106(1.0 m1);第3组:为Tac处理组,术前7 d经受者的尾静脉注射经Tac处理的imDC 2×106(1.0 m1).术后观察:移植心脏的存活时间、受者与供者及无关供者(Lewis大鼠)的单向混合淋巴细胞反应(MLR)、心肌组织病理学表现及血清中白细胞介素(IL)-2、IL-4、IL-10和γ干扰素(IFN-γ)的水平变化.结果 第1、2、3组移植心脏的存活时间分别为(8.57±1.34)d、(20.92±2.68)d和(33.30±3.92)d.各组之间比较,差异均有统计学意义(P＜0.01);第2、3组受者对供者的MLR刺激指数较第1组明显降低,而对无关供者的MLR刺激指数则与第1组相近;各组受者血清IL-2、IFN-γ、IL-4、IL-10浓度问差异有统计学意义(P＜0.01),第3组IL-2和IFN-γ(代表TH1细胞)水平明显降低,而IL-4和IL-10(代表TH2细胞)水平明显增高.结论 imDC能够延长大鼠心脏移植后的存活时间,经Tac处理的imDC能够进一步加强这种作用;且imDC所诱导的免疫低反应性是供者特异性的.其机制可能主要与调节T淋巴细胞免疫应答类型(TH1至TH2的免疫偏移)和诱导T淋巴细胞免疫应答降低有关.     

大鼠心脏移植排斥反应时细胞间粘附分子-1的表达及霉酚酸酯对其的抑制作用

目的　探讨大鼠同种异位心脏移植排斥反应期间移植心组织细胞间粘附分子-1（ICAM-1）的表达及霉酚酸酯（MMF）对移植心ICAM-1表达和排斥反应的抑制作用。方法　建立大鼠心脏腹腔移植模型,设Wistar到Wistar大鼠的同系心脏移植对照组、SD大鼠到Wistar大鼠的同种移植组和同种移植MMF治疗组。采集移植心组织标本行免疫组织化学和组织病理学检查,应用多媒体彩色图文分析系统对移植心组织ICAM-1的表达进行定量检测。结果　对照组移植心组织ICAM-1表达较弱;同种移植组在排斥反应期间移植心组织毛细血管内皮细胞ICAM-1的表达强度和数量明显增加,且伴有大量淋巴细胞浸润;MMF治疗组移植心仅微弱表达ICAM-1,同时少有淋巴细胞浸润;检测移植心组织ICAM-1的表达改变比普通组织病理学检查可以提早2～3d发现排斥反应。结论　ICAM-1的表达水平与排斥反应的发生和发展有关;MMF能显著抑制移植心ICAM-1的表达和淋巴细胞的浸润,明显延长移植物的存活。     

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.     

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.     

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.     

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.