门静脉注射供体脾细胞诱导大鼠移植肾长期存活

目的 :探讨门静脉内注射供体脾细胞诱导移植肾的免疫耐受情况。方法 :实验组 Wistar大鼠在肾移植同时将经过预处理的供体 SD大鼠脾细胞注入门静脉 ,对照组则注入生理盐水 ,然后用环孢素 A治疗 1周 ,并以大鼠平均存活时间为标准比较两组结果。结果 :对照组平均存活( 1 0 .5± 2 .1 ) d,实验组为 ( 72 .2± 32 .0 ) d( P <0 .0 1 )。实验组在肾移植 60 d后 ,再移植 SD大鼠和Lewis大鼠的皮肤 ,发现 SD大鼠的皮肤不被排异 ,Lewis大鼠的皮肤出现排异。结论 :门静脉内注射供体脾细胞可诱导肾移植免疫耐受 ,并且这种耐受具有特异性。     

组织原卟啉IX与大鼠大肠癌在体自体荧光差异的相关性研究

目的探讨组织原卟啉IX含量与大鼠大肠癌在体自体荧光差异的相关性.方法 60只SD大鼠以1,2-二甲肼(Dh)25mg/kg体重注射腹腔,1周1次,持续18周,成功诱导大鼠大肠癌.20周后以370nm激光诱导自体荧光检测分析系统采集实验组大鼠癌组织和正常组织 400～ 700nm范围内的在体自体荧光;采用荧光分光光度计检测癌组织原卟啉IX、正常组织原卟啉IX.结果各组组织在体自体荧光光谱460nm左右处大多有荧光峰;73%的进展期癌组织、69%的早期癌组织在635nm附近有荧光峰.早期癌组和进展期癌组I 635 /I 460 值较正常组大,差异有显著性 (P< 0.05), 早期癌组和进展期癌组I 635 /I 460 值差异无显著性 (P> 0.05); 正常组织原卟啉IX、早期癌组的组织原卟啉IX、进展期癌组织原卟啉IX含量分别为 (317.099± 16.859) ng/g组织、 (416.814± 6.786)ng/g组织和 (606.874± 21.798) ng/g组织,早期癌组和进展期癌组织原卟啉IX较正常组织原卟啉IX大,差异有非常显著性 (P< 0.001),进展期癌组织原卟啉IX较早期癌组织原卟啉IX大,差异有非常显著性 (P< 0.001).结论大鼠正常大肠组织在体自体荧光和大鼠大肠癌在体自体荧光635nm存在差异.635nm处的差异可能是组织原卟啉IX内源性积聚引起的.     

休克期切痂对烫伤大鼠全身和肠道局部免疫功能的影响

目的　观察休克期切痂对烫伤大鼠全身和肠道局部免疫功能的影响 ,探讨其可能的机制。　方法　选用 96只Wistar大鼠。取其中 2 4只大鼠的躯干部皮肤冻存于液氮中 ,另取 8只作正常对照组。余下 6 4只造成 30 %TBSAⅢ度烫伤后 ,随机分为A组 2 4只 ,伤后不作任何处理 ;B组 2 4只 ,伤后 2 4h腹腔注射等渗盐水 5 0ml/kg,一次性切痂后用上述冻存异体皮覆盖 ;C组 1 6只 ,伤后 72h进行处理 ,方法同B组。检测A、B组大鼠伤后 2、4、8d和C组伤后 4、8d及正常对照组大鼠的脾淋巴细胞增殖功能、血浆和肠组织白细胞介素 (IL)2水平、肠黏液分泌型免疫球蛋白A(sIgA)及肠组织中二胺氧化酶 (DAO)含量的变化。　结果　各时相点下A、B、C组大鼠脾淋巴细胞增殖功能、血浆IL 2水平、肠组织IL 2及肠黏液sIgA含量均较正常对照组减少。B组伤后 4、8d和C组伤后 8d的脾淋巴细胞增殖功能接近正常对照组 ,血浆和肠组织IL 2水平明显高于A组 (P <0.0 1)。伤后 4、8d,B组肠黏液sIgA含量分别为 (3.5 1± 2 .1 4 )、(3.0 3± 0 .95 )mg/g,C组分别为 (1 .4 0± 0 .6 4 )、(1 .5 2± 1 .2 6 )mg/g,B组较C组增加近 1倍 (P 0.0 1 )。A组伤后 4、8d肠组织DAO活性低于正常对照组和B组 (P 0.0 5)。结论　休克期切痂有助于烫伤大鼠全身和肠道     

丹参酮ⅡA抑制腹主动脉瘤基质金属蛋白酶-2及诱导型一氧化氮合酶的研究

目的 观察丹参酮ⅡA对胰弹力蛋白酶灌注制作的大鼠腹主动脉瘤(AAA)模型中基质金属蛋白酶-2( MMP-2)和诱导型一氧化氮合酶(iNOS)的抑制作用.方法 将SD雄性大鼠36只随机分成实验组、对照组、空白组3组,每组12只.实验组与对照组应用胰弹力蛋白酶灌注方法制作AAA模型,空白组给予生理盐水灌注.实验组全程接受腹腔内注射丹参酮ⅡA2mg/(天·只),对照组与空白组给予生理盐水注射.术前和术后第5、12、18、24天使用彩色超声仪测量动脉瘤最大处内径,并测量动脉收缩压.术后24 d取腹主动脉组织标本观察组织学变化,应用免疫组织化学、Western blot、逆转录-聚合酶链反应(RT-PCR)方法进行定量观察.结果 术后第1周起实验组腹主动脉直径明显小于对照组(P＜0.01),且各组血压无明显变化(P＞0.05).实验组标本中弹力纤维含量明显高于对照组(P＜0.01),而MMP-2和iNOS蛋白表达则明显较对照组减少(P＜0.01).实验组MMP-2 mRNA表达较对照组明显抑制(P＜0.01).结论 丹参酮ⅡA能够通过下调MMP-2和iNOS表达而抑制大鼠AAA的扩张.     

非细菌性前列腺炎动物模型的建立及环氧合酶-2测定

目的 探讨非细菌性前列腺炎的动物模型建立方法及慢性非细菌性前列腺炎(CNP)的发病机制.方法 成年雄性SD大鼠72只,随机分为3组,每组24只:实验组用大鼠膀胱穿刺抽出尿液前列腺内注射建立前列腺炎模型,对照组用无菌生理盐水前列腺内注射,假手术组大鼠前列腺仅做针刺处理.模型建立后第1、3、7天分别处死大鼠8只观察前列腺大体形态,HE染色光镜观察,免疫组织化学法检测环氧合酶-2(COX-2)在模型中的表达.结果 实验组前列腺炎症变化较对照组及及假手术组明显,第1、3、7天随着时间延长实验组前列腺内炎症程度渐好转.免疫组织化学显示实验组COX-2染色强度为87.5%,较对照组(25.0%)及假手术组(12.5%)明显增强(P＜0.05);随着时间延长C0X-2染色强度有明显下降(P＜0.05).结论 尿液刺激导致前列腺内COX-2升高可能与CNP的发病机制有密切关系.     

血小板源性生长因子BB对大鼠肌腱愈合和肌腱粘连的影响

目的 了解血小板源性生长因子BB(PDGF-BB)基因转染大鼠肌腱细胞对肌腱愈合及肌腱粘连的影响. 方法 将90只SD大鼠制成跟腱损伤模型,按随机数字表法分为3组,每组30只:实验组,肌腱断端注射20μL转染PDGF-BB基因的大鼠肌腱细胞(1×108个/mL);对照组,肌腱断端注射20μL未行转染的大鼠肌腱细胞(1×108个/mL);空白对照组,不做任何处理.6-0丝线行改良Kessler法缝合跟腱,管型石膏固定1周.通过基因测序及RT-PCR鉴定转染PDGF-BB基因的大鼠肌腱细胞.分别于术后3 d和1、2、4、8周取各组大鼠肌腱组织样本,行大体、组织学观察以及生物力学检测,对比各组肌腱粘连度、组织中Fb数量与胶原纤维含量、肌腱最大抗拉力及最大滑动距离、组织中PDGF-BB的浓度.对数据行t检验. 结果(1)转染的肌腱细胞经RT-PCR以及基因测序证实在体外稳定表达PDGF-BB mRNA.(2)各组大鼠术后3 d肌腱均出现较明显肿胀及炎性细胞浸润,实验组改变较其他组明显轻微;随后各组情况均逐渐好转.术后4、8周肌腱粘连度分级组间比较未见明显差异.(3)实验组Fb数在术后2、4、8周显著低于对照组和空白对照组(t值分别为2.94、4.26、5.76和4.00、3.83、6.12,P＜0.05或P＜0.01).(4)实验组术后4周胶原纤维含量为(43±6)%,较对照组[(55±8)%]与空白对照组[(61±8)%]显著下降(t值分别为2.94和4.41,P＜0.05或P＜0.01).(5)术后4、8周实验组肌腱最大滑动距离为(3.25±0.33)、(3.65±0.21)mm,显著高于对照组的(2.29±0.40)、(2.21±0.37)mm和空白对照组的(2.01±0.23)、(1.89±0.24)mm(t值分别为4.53、8.29和7.55、13.52,P值均小于0.01),但其肌腱最大抗拉力与另2组比较差异无统计学意义(t值分别为0.41、0.41和0.77、0.72,P值均大于0.05).(6)术后3 d和2、4周,实验组肌腱组织中PDGF-BB浓度为(12.95±1.36)、(8.32±0.94)、(9.10±1.06)ng/mL,均显著高于对照组的(1.13±0.21)、(2.07±0.48)、(3.85±0.39)ng/mL(t值分别为21.04、14.50、11.39,P值均小于0.01). 结论 转染PDGF-BB基因肌腱细胞有促进肌腱内源性愈合、减轻肌腱粘连的作用.     

神经鞘内转染siRNA-p300对大鼠神经病理痛阈值的影响

目的:探讨神经鞘内转染p300si RNA(si RNA-p300)对大鼠神经病理痛阈值的影响。方法:成年雄性清洁级SD大鼠27只随机分为假手术组、对照组和实验组,每组9只。对照组和实验组应用坐骨神经压迫损伤建立神经病理性痛模型并鞘内置管,分别鞘内转染无关4μg si RNA和4μg si RNA-p300。假手术组单纯进行模拟手术并注射等量生理盐水。分别于转染前及注射后2、4、6、8、10、12和14 d分别检测3组大鼠痛阈分值,于注射后14 d处死大鼠,取腰段脊髓采用Western-blot法检测大鼠脊髓中p300表达水平。结果:与假手术组(21.22±1.56)比较,对照组(14.33±4.02)和实验组(13.66±2.30)大鼠疼痛阈值在转染后第2 d开始显著降低(P0.05)。与对照组(8.98±2.89)比较,实验组(11.23±2.20)大鼠疼痛阈值在转染后第6天开始显著升高(P0.05);假手术组、对照组和试验组p300相对表达量分别为0.11±0.03、0.67±0.18和0.22±0.04,与假手术组比较,对照组和实验组p300表达显著上调(P0.05);与对照组比较,实验组p300表达明显下调(P0.05)。结论:鞘内注射si RNA-p300可显著降低大鼠神经病理性疼痛,提高痛阈。     

联合输注供体特异性不成熟树突状细胞及环胞素A对受体Th1/Th2淋巴细胞分化的影响

目的探讨联合应用体外培养供体特异性不成熟树突状细胞及环胞素A(CsA)对受体体内Th1 /Th2淋巴细胞分化的影响。方法建立大鼠同种异体原位肝移植模型 ,88只LWE大鼠和SD大鼠随机分为 3组 :(1 )对照组 :术后不予免疫抑制剂 ;(2 )CsA组 :术后第 2天起隔日腹腔内按1mg/ 1 0 0 g 体重注射CsA ,共 3次 ;(3)CsA DC组 :除术后按CsA组腹腔注射CsA外 ,第 8天阴茎背静脉注射 1 0 6个供体骨髓体外培养的不成熟树突状细胞 (DCim)。术后观察各组的生存时限及 5、1 0、1 5、2 5d分别取标本行肝脏免疫病理学检查、腹腔淋巴结中INF γmRNA、IL 6mRNA含量的检测。结果CsA DC组的生存时限为 (2 7 0± 1 0 )d ,较对照组及CsA组显著延长 (P <0 0 5 ) ;CsA DC组受体腹腔淋巴结中的INF γmRNA含量较对照组及CsA组低 (P <0 0 5 ) ,而IL 6mRNA含量则较前两组升高 (P <0 0 5 )。结论联合应用环孢素A和体外培养的供体特异性DCim后受体体内Th2型淋巴细胞含量升高 ,而Th1型淋巴细胞含量降低 ;通过调节受体体内Th1 /Th2淋巴细胞比例是其降低大鼠肝移植术后免疫排斥反应的机制之一     

塞来昔布对大鼠大肠癌生长的抑制作用

目的 观察选择性环氧合酶(COX-2)抑制剂塞来昔布对二甲肼(DMH)诱导的SD大鼠大肠癌生长的抑制作用.方法 健康雄性SD大鼠100只,随机分为4组:空白对照组(20只),造模组(30只),干预组(30只)及干预对照组(20只).空白对照组:皮下注射与造模组DMH等体积的生理盐水,每周1次;造模组:利用大鼠大腿内侧(双后肢交替使用)皮下注射DMH(每周20 mg/kg);干预组:DMH皮下注射量同造模组,同时给予塞来昔布(20 mg/kg)灌胃,隔天1次;干预对照组:给予与干预组等体积的塞来昔布灌胃,隔天1次,持续25周.各组于第15、20、25周分别处死大鼠2只,行苏木素-伊红(H F)染色,光镜下观察病理变化,剩余大鼠第30周全部处死.结果 实验30周后,空白对照组和干预对照组大鼠大肠末见肿瘤形成,造模组大鼠成瘤率为89.47％,干预组大鼠成瘤率为56.52％,两组差异有统计学意义(P＜0.05);造模组大鼠成癌率为68.42％,干预组大鼠成癌率为34.78％,两组差异有统计学意义(P＜0.05);造模组单个大鼠大肠产生的肿瘤数和单个肿瘤直径分别为(2.64±0.86)个和(4.06±1.14) mm;干预组单个大鼠大肠产生的肿瘤数和单个肿瘤直径分别为( 1.85 ±0.80)个和(3.08±0.86) mm,两组差异有统计学意义(P＜0.05).结论 选择性COX-2抑制剂塞来昔布对DMH诱导的SD大鼠大肠癌生长有抑制作用.     

肢体缺血大鼠骨髓内皮祖细胞的动员与组织血管新生的相关性研究

目的　探讨肢体缺血因素对骨髓内皮祖细胞 (EPC)的动员及肢体血管新生的影响。方法　切除、结扎单侧股总、股浅动脉建立大鼠后肢缺血模型 ,另设对照组。 1周后通过细胞培养 ,观察外周血EPC数量的变化 ,4周后检测缺血组织微血管密度 (MVD )及血管内皮生长因子(VEGF)的表达情况。结果　实验组外周血EPC (4 8.6± 7.5 )个 /mm2 较对照组 (2 3 .1± 4.3 )个 /mm2 明显增加 (P <0 .0 1) ;组织MVD (2 2 4.84± 5 .87)n/mm2 显著高于对照组 (13 6.3 0± 4.5 2 )n/mm2 (P <0 .0 1) ;实验组缺血组织VEGF表达明显增强 (吸光度值A :0 .162± 0 .0 18) ,对照组仅少量表达 (A :0 .0 5 5± 0 .0 0 6) ;外周血EPC与组织MVD、VEGF吸光度之间有非常显著相关 (P <0 .0 1)。结论　肢体缺血通过动员骨髓EPC ,促进缺血组织的新血管生成 ,改善局部供血 ,达到部分代偿目的。     

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.