他克莫司联合青藤碱抑制大鼠心脏移植急性排斥反应

目的 探讨青藤碱（SIN）对大鼠心脏移植急性排斥反应抑制作用的机制，并评价青藤碱与他克莫司（FK506）联合作用的效果。方法 以PVG大鼠为供者，DA大鼠为受者，建立同种异体心脏移植模型。将受者随机分为4组，每组20只。对照组：采用生理盐水3ml·kg^-1·d^-1灌胃；SIN组：腹腔注射SIN 30mg·kg^-1·d^-1；FK506组：采用FK506 0．25mg·kg^-1·d^-1灌胃；联合组：腹腔注射SIN 30mg·kg^-1·d^-1并联合应用FK506 0．25mg·kg^-1·d^-1灌胃。各组均在术后24h内用药，用药时间共7d。观察各组移植心存活时间，术后第7d取部分受者的移植心做病理检查，检测外周血中肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）、T细胞亚群、一氧化氮合酶（iNOS）等的浓度。结果 对照组移植心平均存活时间为（6．0±1．054）d，FK506组为（10．2±2．2）d，SIN组为（9．5±1．84）d，联合组为（16．2±2．1）d，联合组与其他3组比较，差异有统计学意义（P〈0．05）。SIN组、FK506组及联合组与对照组比较，外周血中TNF-α、IFN-γ、iNOS的表达明显减少（P〈0．05），CD4^＋T细胞亚群增殖率也明显下降（P〈0．05）。其中联合组的效果更优于SIN组和FK506组（P〈0．05）。结论 SIN能明显地抑制大鼠心脏移植急性排斥反应的发生，与FK506联合应用有协同作用。     

慢性移植肾肾病患者将环孢素A转换为他克莫司的临床观察

目的 探讨慢性移植肾肾病（CAN）患者以他克莫司（FK506）替换环孢素A（CsA）的临床效果。方法 根据是否以FK506来替换CsA，将97例诊断为CAN的患者分成两组，CsA组39例，维持原免疫抑制方案（CsA、霉酚酸酯和泼尼松联用）不变，采用替换方案的FK506组58例，除将CsA切换为FK506外，其它用药同CsA组。两组均随访1年以上，监测血胆固醇总量（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、尿素氮、肌酐、白蛋白及24h尿蛋白定量等生化指标的变化情况，观察随访期间药物的不良反应。结果 CsA组的血脂水平无明显变化，而FK506组除HDI，外，TC、LDL及TG等均较CsA组有不同程度的下降（P〈0．05，P〈0．01）。CsA组血肌酐继续上升，而FK506组的血肌酐下降，两组比较，差异有统计学意义（P〈0．01）；CsA组有3例移植肾功能丧失。FK506组需用降压药维持血压的例数少于CsA组（P〈0．05）；FK506组血清白蛋白水平显著高于CsA组（P〈0．05），24h尿蛋白定量显著低于CsA组（P〈0．01）。FK506组震颤发生率较CsA组高（P＜0．01），而高血压、毛发增多及牙龈增生的发生率均显著低于CsA组（P＜0．05）。结论 CAN患者在以FK506替换CsA后，脂质代谢异常等到明显改善，肾功能减退得到延缓。     

ICAM-1在小鼠到大鼠心脏移植中的表达及来氟米特与环孢素A对其表达的影响

目的：探讨细胞间粘附分子1（ICAM-1）在小鼠到大鼠异种心脏移植中的表达，以及来氟米特（LeD和环孢素A（CsA）对其表达的影响。方法：以NIH小鼠为供者，Wistar大鼠为受者，施行异位（颈部）心脏移植，实验分4组进行，CsA组受者术后接受CsA腹腔注射，Lef组受者术后接受Lef灌胃，联合用药组受者术后接受Lef和CsA治疗，另设空白对照组，受者术后不进行任何处理。以移植心脏停跳作为排斥反应的终点，采用免疫组化和蛋白印迹杂交法检测移植心肌组织中ICAM-1蛋白的表达。结果：空白对照组、CsA组、Lef组及联合用药组移植心的存活时间分别为（2．17±0．41）d、（2．50±1．05）d、（4．17±1．33）d和（6．50±2．56）d，联合用药组明显长于其它三组（P〈0．05），Lef组明显长于空白对照组（P〈0．05）。移植心脏组织中ICAM-1蛋白的表达强度（电泳条带积分吸光度值），空白对照组为155．40±5．33，CsA组为150．73±5．13，Lef组为104．65±6．15，联合用药组为29．24±2．76，联合用药组的积分吸光度值明显低于其它三组（P〈0．05），Lef组的积分吸光度值明显低于CsA组和空白对照组（P〈0．05）。结论：小鼠到大鼠的异种心脏移植中ICAM-1表达明显，联合应用Lef和CsA可显著抑制ICAM-1在移植心脏中的表达。     

用他克莫司替换环孢素A预防和治疗肾移植后慢性移植肾肾病

目的 观察用他克莫司（FK506）替换环孢素A（CsA）预防和治疗肾移植术后慢性移植肾肾病的有效性和安全性。方法 回顾性分析36例肾移植术后移植肾功能异常，病理检查确诊为慢性移植肾肾病（CAN）患者的临床资料。所有患者术后均采用以CsA为主的免疫抑制方案，临床确诊为CAN后，用FKS06替换CsA。FK506的起始剂量为原CsA剂量的1／50～1／100，维持剂量则根据患者的体重、发病情况、肾移植时间及FK506的血药谷值浓度确定，其他免疫抑制剂用量不变。观察换药后的移植肾功能变化，同时监测血糖、血脂和FK506的血药浓度。结果 用FK506替换治疗6个月后，患者的移植肾功能较替换前明显好转（P＜0．05），胆固醇、甘油三酯较替换前降低（P＜0．05），但血糖升高，出现新发糖尿病2例。结论 用FK506替换CsA可改善移植肾功能，提高移植肾的长期存活率。     

异基因造血干细胞移植后动态监测调节性T淋巴细胞的临床意义

目的探讨监测调节性T淋巴细胞（Treg）的动态变化在异基因造血干细胞移植（allo-HSCT）中的临床意义。方法选择45例allo-HSCT患者，其中31例采用短程甲氨蝶呤（MTX）联合环孢素A（CsA）预防移植物抗宿主病（GVHD），另14例加用霉酚酸酯（MMF）和达利珠单抗（抗CD25单克隆抗体）强化GVHD的预防。采用流式细胞术动态监测allo-HScT患者移植预处理前、移植后2、4、8、12周时及发生急性移植物抗宿主病（aGVHD）时外周血Treg的水平；分析Treg水平的变化与aGVHD发生的相互关系。结果45例患者中，发生Ⅱ～Ⅳ度aGVHD10例。移植后8和12周时，未使用达利珠单抗组中发生Ⅱ～Ⅳ度aGVHD较发生0～I度aGVHD的患者外周血Treg水平显著降低，差异有统计学意义（P〈0．05）；患者发生Ⅱ～Ⅳ度aGVHD后，外周血Treg水平较发生前显著降低，差异有统计学意义（P〈0．05）。使用达利珠单抗组的患者外周血Treg水平在各时间点均明显降低，各时点间比较，差异均无统计学意义。结论Treg的动态变化与aGVHD的关系密切，可作为临床监测aGVHD发生的重要指标之一；达利珠单抗的应用显著降低了外周血Treg的水平，其对aGVHD的预防作用有待今后深入研究。     

他克莫司在胰、肾同期联合移植中的应用体会

目的回顾性总结他克莫司（FK506）在胰、肾同期联合移植（SPK）中的应用经验。方法37例SPK受者，术后早期采用抗淋巴细胞球蛋白（最初3例）或抗白细胞介素2受体单克隆抗体（34例）诱导治疗，采用FK506、霉酚酸酯（MMF）和皮质激素维持治疗。FK506于术后第3～4天开始口服，起始剂量为0．05～0．08mg·kg^-1·d^-1，3～5d后根据血药浓度调整用量，血FK506的浓度谷值，术后1个月内维持在10～12μg／L，2～3个月为6～10μg／L，3个月后为4～8μg／L。结果37例术后均停用胰岛素，仅1例（2．7％，1／37）术后6个月死于急性心肌梗死，受者、移植胰和移植肾1年存活率均为97％。空腹血糖恢复正常的时间为（13．4±8．9）d。28例1型糖尿病患者术后空腹血糖恢复正常的时间为（9．7±3．2）d，9例2型糖尿病患者术后空腹血糖恢复正常的时间显著延长，为（23．0±11．7）d。1年内急性排斥反应发生率为13．5％（5／37），其中4例为单纯移植肾排斥反应，1例同时累及移植胰腺和肾脏；2例经激素冲击治疗后逆转，1例经激素和抗淋巴细胞球蛋白治疗逆转，另2例经激素冲击治疗后，血肌酐一度下降，但2～3个月后因再次发生排斥反应，血肌酐逐渐上升，恢复血液透析，但移植胰功能良好，其后行再次肾移植。结论以FK506为基础的免疫抑制能安全、有效地预防SPK后的排斥反应。     

乙型肝炎病毒携带者肾移植后应用他克莫司和环孢素A对肝功能影响的比较

目的 探讨乙型肝炎病毒携带者肾移植术后应用他克莫司（FK506）和环孢素A（CsA）对肝功能的影响。方法 73例乙型肝炎病毒（HBV）携带者接受肾移植，术前患者的肝功能正常，HBVDNA阴性。术后将患者分为两组：FK506组40例，术后服用FK506、霉酚酸酯（MMF）及泼尼松（Pred）预防排斥反应；CsA组33例，术后服用CsA、MMF及Pred预防排斥反应。术后追踪随访1～6年，观察两个组患者肝功能损害情况以及HBVDNA阳性率，发生肝功能损害时，调整免疫抑制剂的用量，并给予护肝治疗。结果 术后FK506组有4例（10．0％）、CsA组有16例（48．5％）发生肝功能损害，FK506组有2例（5．0％）、CsA组有9例（27．3％）HBVDNA转阳性，两组比较，差异均有统计学意义（P＜0.05）。CsA组肝功能损害的16例中，10例将CsA切换为FK506，另6例治疗方案不变，结果转换药物者肝功能恢复正常的时间明显短于未转换者（P〈0．01），且治疗1～2周时的丙氨酸转氨酶、天冬氨酸转氨酶和胆红素总量的水平也明显低于未转换者（P＜0．05，P＜0．01）。结论 与CsA相比，乙型肝炎病毒携带者肾移植术后应用FK506可降低肝功能损害的发生率，减少乙型肝炎复发。     

血管内皮祖细胞促进游离移植脂肪颗粒组织存活的实验

目的探讨血管内皮祖细胞（endothelial progenitor cell，EPC）移植促进游离移植的脂肪颗粒组织的血管新生，提高移植脂肪颗粒组织存活率。方法体外分离、培养人脐血中EPCs，然后与来自人体的脂肪颗粒组织混合移植于裸鼠背部。结果脐血中分离培养的EPCs表达血管内皮细胞生长因子受体（KDR）及细胞表面标记CD34、CD133，EPCs与脂肪颗粒组织混合移植到裸鼠3个月后，EPCs整合到缺血部位新生血管中，与对照组的脂肪颗粒组织存活率分别为（89．3±6．8）％、（42．2±2．5）％（P〈0．05），而且实验组与对照组脂肪颗粒组织周边区毛细血管密度差异有统计学意义（P〈0．05）。术后3个月2组脂肪颗粒组织周边区的EPCs密度分别为（95．2±10．5）个／mm^2、0个／mm^2（P％O．05）。结论体外培养的脐血EPCs移植体内可促进游离移植的脂肪颗粒组织的血管新生，提高存活率。     

氨磷汀在体外减轻足叶乙甙所致的骨髓间充质干细胞损伤

目的研究氨磷汀在体外对化疗药物所致的骨髓间充质干细胞（MSCs）损伤的影响，为其应用于慢性粒细胞白血病（CML）患者的造血干细胞移植提供实验依据。方法采集CML患者的骨髓细胞，应用极限稀释法获取单克隆来源的MSCs，并在低血清培养液中培养和扩增。按实验分组分别加入氨磷汀（氨磷汀组）、足叶乙甙（VP-16组）、氨磷汀和足叶乙甙（联合处理组），并设没有处理的对照组。在药物作用一定时间后，计数MSCs，绘制生长曲线；流式细胞仪检测MSCs的免疫表型及凋亡率；在甲基纤维素半固体培养中检测MSCs作为滋养层支持造血的能力。结果MSCs生长曲线显示，与对照组相比，氨磷汀组的MSCs生长未受明显影响，联合处理组MSCs的生长显著好于沿16组。培养48h后，对照组、氨磷汀组、联合处理组和VP-16组的MSCs凋亡率分别为（4．9±0．8）％、（5．6±1．2）％、（18．7±3．4）％和（33．8±5．1）％，氨磷汀组与对照组相比，差异无统计学意义；联合处理组高于对照组，但明显低于VP-16组（P〈0．05）。形成粒-单核系集落、红系集落和多系集落的产率，氨磷汀组与对照组间的差异无统计学意义，联合处理组低于对照组（P〈0．05），但显著高于VP-16组（P〈0．05）。氨磷汀作用前后未见MSCs免疫表型发生明显改变。结论氨磷汀在体外对CML患者骨髓来源MSCs的增殖、凋亡、造血支持能力以及免疫表型无明显影响，但能显著改善足叶乙甙对MSCs所致的生长抑制及功能损伤，提示在预处理中加用氨磷汀可能成为促进CML患者造血干细胞移植后造血恢复的一种新策略。     

大鼠肝移植后早期血清一氧化氮的变化及其意义

目的探讨大鼠肝移植后早期血清一氧化氮（NO）的变化情况及其意义。方法将SD大鼠随机分成A、B、C三组，进行肝移植．供、受者均为SD大鼠。A组于移植肝恢复血流2h、B组于移植肝恢复血流4h、C组于移植肝恢复血流6h时采取受者的下腔静脉血和左肝叶组织．测定血清丙氨酸转氨酶（ALT）和NO含量．免疫组化法测定移植肝组织中核因子．κB p65亚单位（NF-κB p65）的表达，并观察肝组织病理学变化；每组均于移植肝恢复血流时收集5min的胆汁，测量5min胆汁分泌量。结果A组的5min胆汁分泌量为（3．73±1．11）μl．明显高于B组的（2．35±0．92）μ和C组的（2．23±0．81）μl（P〈0．05）。A组血清ALT含量为（468±36）IU／L．B组为（619±49）IU／L．C组为（820±65）IU／L，A组明显低于B、C组（P〈0．05），B组明显低于C组（P〈0．05）。A组血清NO含量为（14．2±1．5）μmol／L，明显高于B组的（10．5±1．2）μmol／L和C组的（10．3±1．1）μmol／L（P〈0．05）。A组肝组织中NF-κB p65表达阳性细胞百分率为（23．5±1．9）％．B组为（43．8±3．8）％，C组为（48．6±5．1）％．A组明显低于B、C组（P〈0．05）。病理学观察显示．随着移植肝脏再灌注时间的延长，肝组织损伤呈进行性加重。Pearson相关性分析提示．NO与血清ALT水平及NF-κB p65表达呈明显的负相关（r值分别为-0．74和-0．77，P〈0．01）。结论移植肝脏再灌注早期．血清NO下降，NF-κB的活性逐渐增强．移植肝脏的功能和组织损伤呈加重趋势。     

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.     

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.     

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.