利用RNA干扰诱导产生的CD8+CD28-抑制性T淋巴细胞的免疫学特性

目的 探讨通过RNA干扰技术诱导产生的CD8+ CD28-抑制性T淋巴细胞(Ts细胞)的免疫学特性.方法 取SD大鼠骨髓,培养分离树突状细胞(DC),设计、合成主要组织相容性复合物(MHC)Ⅰ类小片段干扰RNA(siRNA),以MHC Ⅰ siRNA转染DC.先以Wistar大鼠肠系膜淋巴组织液刺激转染MHCI siRNA的DC,然后将DC与从SD大鼠脾脏分离得到的CD8+T淋巴细胞共同培养,通过磁珠法分离出Ts细胞.分别在由SD大鼠脾脏淋巴细胞(反应细胞)和Wistar大鼠肠系膜淋巴组织细胞(刺激细胞)组成的混合淋巴细胞培养体系中加入数量不等的Ts细胞,检测反应细胞增殖情况;分别以Wistar大鼠肠系膜淋巴组织细胞和卵白蛋白(OVA)刺激SD大鼠脾脏淋巴细胞,然后再按不同比例加入Ts细胞,检测各组脾脏淋巴细胞的增殖情况;在由SD大鼠脾脏淋巴细胞、Wistar大鼠肠系膜淋巴组织液和Ts细胞组成的混合淋巴细胞培养体系中加入可溶性重组白细胞介素2(rrIL-2),观察IL-2对Ts细胞功能的影响;采用实时定量聚合酶链反应(PCR)测定Ts细胞中转化生长因子β(TGF-β和γ干扰素(IFN-γ)mRNA的表达,流式细胞仪和实时PCR检测Ts细胞上CD25分子的表达.结果 Ts细胞对SD大鼠脾脏淋巴细胞和Wistar大鼠肠系膜淋巴组织细胞之问的混合淋巴细胞反应(MLR)具有抑制作用,但对于SD大鼠脾脏淋巴细胞和OVA之间的MLR则无抑制作用.在SD大鼠脾脏淋巴细胞、Wistar大鼠肠系膜淋巴组织液和Ts细胞组成的混合淋巴细胞培养体系中加入rrIL-2后,SD大鼠脾脏细胞的增殖并无明显增加(P＞0.05).与CD8+CD28+T淋巴细胞和CD8+ T淋巴细胞比较,Ts细胞的TGF-β和IFN-γ mRNA的表达量明显升高(P＜0.01,P＜0.05),而CD25的表达量明显降低(P＜0.05).结论 采用经MHC I siRNA干扰的DC能够诱导CD8+T淋巴细胞产生CD8+ CD28-Ts细胞;Ts细胞在体外具有免疫抑制特性,其免疫抑制作用不被外源性IL-2所逆转,且其免疫调节作用具有抗原特异性.     

人CD8+CD28-抑制性T淋巴细胞的体外扩增及其抗原特异性调节作用

目的 探讨在体外大量扩增CD8+CD28-抑制性T淋巴细胞(Ts细胞)的方法,并检验其免疫调节作用.方法 分离健康志愿者全血中CD8+T淋巴细胞,在含不同细胞因子和异体抗原提呈细胞(APC)的培养条件下进行体外扩增.应用流式细胞术对扩增过程中CD28 -细胞亚群的比例进行监测.分为3组进行混合淋巴细胞培养,反应细胞均为CD4+T淋巴细胞:B-APc组以来源于原致敏供者的APC作为刺激细胞,I-APC组以HLA-A、B、DR全错配的无关供者的APC作为刺激细胞,Dynabeads组以包被有抗CD3和CD28单克隆抗体的免疫微球Dynabeads作为刺激细胞;扩增后的Ts细胞作为第三方调节细胞加入混合淋巴细胞培养中,测定其对CD4+T淋巴细胞增殖的抑制作用.结果 在含白细胞介素2(IL-2)+ IL-7+ IL-15的培养条件下,CD8+T淋巴细胞培养后CD8+CD28-T淋巴细胞亚群的比例最高(P＜0.05).B-APC组不加入Ts细胞时,增殖的CD4+T淋巴细胞比例为66.7％,当加入的Ts细胞与反应细胞的比例分别为0.5∶1、0.1∶1和0.02∶1时,增殖的CD4+T淋巴细胞比例分别为16.5％、34.1％和62.6％.Ts细胞对CD4+T淋巴细胞的增殖有明显抑制作用,而在I-APC组和Dynabeads组中,此抑制作用不明显.结论 应用含IL-2+ IL-7+ IL-15的培养条件联合异体APC刺激可以在体外大量扩增Ts细胞,扩增所得Ts细胞在体外对供者CD4+T淋巴细胞的增殖有明显抗原特异性抑制作用.     

阻断共刺激通路诱导产生免疫无能状态

目的 探讨同时阻断CD40／CDl54和B7／CD28共刺激通路能否诱导产生免疫无能状态以及无能状态的逆转条件。方法 以C3H小鼠脾细胞为刺激细胞，BALB／c小鼠脾细胞为反应细胞，C57BL／6J小鼠脾细胞为第三方细胞，在体外双向混合淋巴细胞培养中加入不同浓度的抗CDl54和抗CD80单克隆抗体，诱导产生无能细胞。在无能细胞中分别加入经7射线照射后的C3H小鼠或C57BL／6J小鼠脾细胞，或者直接加入不同浓度重组小鼠白细胞介素2(nmIL-2)，或者同时加入经7射线照射后的C3H小鼠细胞和不同浓度的mnIL-2刺激，观察无能状态的逆转情况。结果 联合应用抗CDl54和抗CD80单克隆抗体能显著抑制体外双向混合淋巴细胞培养反应的细胞增殖；第三方刺激细胞能够逆转无能细胞的无能状态；单纯加入nmIL-2或C3H小鼠细胞再次刺激不能逆转无能状态，而只有同时加入C3H小鼠细胞和nmIL-2刺激才能逆转无能细胞的无能状态。结论 同时阻断CD40／CDl54和B7／CD28通路能诱导产生抗原特异性的免疫无能状态，而且只有同时给予抗原和外源性IL-2再次刺激才能逆转这种无能状态。     

脂肪干细胞免疫学性状的初步实验观察

目的初步研究脂肪干细胞(Adiposederivedstemcells,ADSC)表面免疫分子的表达以及体外免疫调节功能,以期为组织工程提供同种异体种子细胞来源。方法体外培养人脂肪抽吸术中获取的脂肪干细胞,体外培养至第二代,流式细胞仪检测免疫分子HLA、HLA、B7-1、B7-2、CD40的表达。1×105个/孔ADSC细胞分别刺激单一异体淋巴细胞或混合双向淋巴细胞反应,观察淋巴细胞增殖情况。同时观察ADSC经IFN-γ作用后,免疫分子表达与淋巴细胞增殖的调节情况。结果ADSC表达HLA类分子,但未检测到HLA类分子阳性表达。B7-1(CD80)、B7-2(CD86)、CD28、CD40未见明显阳性表达。人IFN-γ刺激48h后,HLA类分子表达明显增高,HLAI表达未见明显增高。异体或经IFN-γ作用的ADSC均未能刺激异体淋巴细胞增殖。同样数量的ADSC可明显抑制双相混合淋巴细胞增殖,经IFN-γ作用后抑制作用未见明显减弱。结论ADSC具有一定的体外调节淋巴细胞反应的能力,有可能成为组织工程同种异体细胞来源。     

大鼠睾丸支持细胞对骨髓问充质干细胞免疫抑制作用的影响

目的探索睾丸支持细胞（Sertoli细胞）对骨髓间充质干细胞（BMSC）免疫抑制作用的影响,为二者在移植免疫中的联合应用提供思路。方法二步酶解法处理大鼠睾丸,分离Sertoli细胞;Percoll法分离大鼠BMSC;Ficoll法分离淋巴细胞;刀豆蛋白A（ConA）刺激进行T细胞转化试验;将Sertoli细胞、BMSC和Sertoli细胞＋BMSC分别加入未经ConA处理的静止淋巴细胞培养体系和经ConA处理后的T细胞转化体系,MTT法测定淋巴细胞增殖情况,观察BMSC、Sertoli细胞或二者共培养对T细胞活化、增殖的影响。结果 BMSC、Sertoli细胞以及二者共培养对静止的淋巴细胞无明显作用。BMSC、Sertoli细胞及二者共培养对T细胞的活化、增殖均有明显的抑制作用,且Sertoli细胞与BMSC共培养时抑制作用呈现一定的协同性。结论 BMSC和Sertoli细胞均具有负性免疫调节作用,二者共培养可以进一步增强BMSC的免疫抑制效应。     

高迁移率族蛋白B1诱导的树突状细胞对T淋巴细胞增殖及功能性极化的影响

目的 观察高迁移率族蛋白B1(HMGB1)诱导的树突状细胞(DCs)对大鼠脾T淋巴细胞增殖反应及功能性极化的影响,并探讨其作用机制.方法 分离正常Wistar大鼠脾脏DC后置于24孔培养板(1×106/孔),采用1 ms/L的HMGB1刺激48 h,DC与脾T淋巴细胞的细胞比例分别为1:50、1:100、1:150、1:200混合,于共同作用后3、5 d观察脾T淋巴细胞增殖及功能性极化的情况.结果 DC与T淋巴细胞以1:50、1:100、1:150、1:200的比例相互作用,脾T淋巴细胞对丝裂原刺激的增殖反应均明显增强、上清液中干扰素(IFN)-γ含量显著升高和白细胞介素(IL)-4含量明显降低(P《0.01),其中细胞比例1:150组最为明显.脾T淋巴细胞对丝裂原刺激的增殖反应增强、IFN-γ含量增加和IL-4含量降低均以第3天最为显著[分别为(0.646±0.028)、(268.08±14.07)、(6.16±0.59)ng/L,P值均《0.01].结论 HMGB1诱导的DC使脾T淋巴细胞对丝裂原刺激的增殖反应明显增强,并促进T淋巴细胞向Th1功能性极化.     

IL-4与IL-10联合诱导异种骨移植免疫耐受的体外研究

目的　探讨 IL - 4和 IL - 10在诱导异种骨移植免疫耐受中的作用。方法　反应细胞为 BAL B/c小鼠脾淋巴细胞 ,刺激细胞为新西兰白兔血淋巴细胞 ,刺激抗原为兔骨上清液。采用经典的混合淋巴细胞培养法及骨上清液与淋巴细胞混合培养法作为异种骨移植的体外实验模型。在各培养液中分别加入 IL - 4、IL - 10及两者联合应用 ,通过测定其 3H- Td R掺入率 ,观察不同细胞因子对刺激淋巴细胞增殖的影响。结果　无论在细胞刺激组还是骨上清液刺激组 ,IL- 4对淋巴细胞增殖均有显著抑制作用 (P<0 .0 0 1和 P<0 .0 5 ) ,IL- 10未表现出抑制作用 (P>0 .0 5 )。在两组 IL- 4和 IL - 10联合应用均产生比 IL - 4单独应用更为明显的细胞增殖抑制作用 (P<0 .0 0 1和 P<0 .0 5 )。结论　 IL - 4对由细胞或骨上清液刺激产生的淋巴细胞增殖均有很好的抑制作用 ,IL- 10没有表现出抑制作用 ;IL- 4与 IL- 10联合应用有协同抑制作用。     

CTLA4-Ig和IL-4诱导异种骨移植免疫耐受的体外研究

目的探讨CTLA4Ig和IL4在诱导异种骨移植免疫耐受中的作用。方法反应细胞为BALB/c小鼠脾淋巴细胞,刺激细胞为新西兰白兔血淋巴细胞,刺激抗原为兔骨上清液。采用经典的混合淋巴细胞培养法及骨上清液与淋巴细胞混合培养法作为异种骨移植的体外实验模型。在各培养液中分别加入CTLA4Ig、IL4及两者联合应用,通过测定其3HTdR掺入率,观察不同细胞因子对刺激淋巴细胞增殖的影响。结果1细胞刺激组CTLA4Ig和IL4均对淋巴细胞增殖有显著抑制作用P<0.001),CTLA4Ig与IL4联合应用并未显示出比CTLA4Ig单独应用更为明显的细胞增殖抑制作用(P>0.05)。2骨上清液刺激组:CTLA4Ig对细胞增殖无抑制作用(P>0.05),而IL4则有较为显著地细胞增殖抑制作用(P<0.05);CTLA4Ig与IL4联合应用也未产生比单独应用IL4更为明显的细胞增殖抑制作用(P>0.05)。结论CTLA4Ig对由细胞刺激产生的淋巴细胞增殖抑制效果较好,而IL4则对骨上清液刺激的细胞增殖抑制作用更好;CTLA4Ig与IL4联合应用并未产生协同抑制作用。     

抗IL-2R单克隆抗体在肾脏移植中的应用

IL 2和IL 2R的相互作用在T细胞活化、增殖中起关键作用。IL 2Rα单克隆抗体可以对被同种异体移植物激活的T细胞克隆选择性地产生免疫抑制作用 ,从而达到预防急性排斥反应的目的。Ⅲ期临床试验结果表明 ,IL 2Rα单抗da clizumab(Zenapax)和basiliximab(Simulect)可将同种异体移植肾急性排斥反应的发生率降低 2 7～ 40 % ;并未见明显的毒副作用。     

成人骨髓间充质干细胞抑制异体淋巴细胞增殖的实验研究

目的研究成人骨髓间充质干细胞（BMMSCs）的免疫调节作用。方法从成人骨髓中分离和培养间充质干细胞，并通过形态的均一性及流式细胞术检测其表面标志以鉴定纯度。将分离培养的间充质干细胞接种于96孔板中，经丝裂霉素处理后，与异体淋巴细胞共同培养3d；并以单独培养的异体淋巴细胞作为对照组。各组经培养后加入植物血凝素（PHA）刺激72h，用MTT还原法测定细胞增殖率，观察成人骨髓BMMSCs对异体淋巴细胞增殖转化的影响。结果成人BMMSCs与PHA诱导的异体淋巴细胞共同培养组抑制了细胞增殖，其增殖转化抑制率为对照组的60．68％，配对t检验结果显示，两组差异有统计学意义（P〈0．01）。结论成人BMMSCs可以抑制PHA诱导的异体淋巴细胞增殖转化，对同种异体免疫反应具有负调节作用。     

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.     

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.     

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.