冬虫夏草提取物抑制大鼠移植物血管病的实验研究

目的 探讨冬虫夏草提取物抑制大鼠移植动脉硬化的效果及其机制.方法 制备大鼠腹主动脉移植模型,分为4组进行实验:同系对照组供、受者均为Lewis大鼠,生理盐水灌胃60d;同种对照组,以Brown-Norway大鼠(BN大鼠)为供者,Lewis大鼠为受者,生理盐水灌胃60d;低剂量实验组,以BN大鼠为供者,Lewis大鼠为受者,以冬虫夏草提取物(1.5 g·kg-1·d-1)灌胃60 d;高剂量实验组,以BN大鼠为供者,Lewis大鼠为受者,以冬虫夏草提取物(3.0g·kg-1·d-1)灌胃60d.于移植后60 d取移植动脉,HE染色,进行病理学观察;免疫组织化学和蛋白质印迹法检测血管内皮生长因子(VEGF)和血小板衍生生长因子BB(PDGF-BB)在移植动脉中的表达.酶联免疫吸附试验检测受鼠血清中VEGF和PDGF- BB含量.结果 同系对照组移植动脉形态正常;同种对照组移植动脉呈移植物血管病表现,血管内膜显著增厚;2个实验组移植动脉呈内膜炎症改变,内膜厚度与同种对照组相比,差异有统计学意义(P＜0.05).同种对照组移植动脉中VEGF和PDGF-BB的表达高于同系对照组(P＜0.05);2个实验组移植动脉中VEGF和PDGF-BB的表达低于同种对照组(P＜0.05).同系对照组受鼠血清中几乎无VEGF和PDGF-BB;同种对照组血清中VEGF和PDGF-BB浓度高于同系对照组(P＜0.05);和同种对照组相比较,2个实验组血清VEGF和PDGF-BB浓度较低(P＜0.05).结论 冬虫夏草提取物能明显抑制动脉内膜的增生,可缓解慢性排斥反应所致的移植动脉硬化,这种保护作用可能与下调VEGF和PDGF-BB表达有关.     

沙利度胺对大鼠慢性移植物血管病的保护作用

目的探讨沙利度胺对大鼠慢性移植物血管病的保护作用。方法实验分为4组：同种移植对照组,供、受者均为Lewis大鼠,无特殊处理;异种移植对照组,Lewis大鼠接受Brown-Norway（BN）大鼠腹主动脉移植（BN-Lewis）;沙利度胺小剂量组（50mg·kg-1·d-1,BN-Lewis）;沙利度胺大剂量组（100mg·kg-1·d-1,BN-Lewis）。于移植后60d取移植动脉,分别进行组织病理学观察、测量内膜厚度,免疫组织化学法和蛋白质印迹法检测TNF-α及上皮细胞增殖细胞核抗原（PCNA）在移植动脉中的表达。结果同种移植对照组移植动脉形态正常;异种移植对照组移植动脉呈移植物血管病表现,血管内膜增厚;沙利度胺小剂量及大剂量组移植动脉呈内膜炎改变,内膜厚度比异种移植对照组减小（P〈0．05）。与异种移植对照组相比,沙利度胺小剂量组和大剂量组移植动脉TNF-α及PCNA蛋白表达量降低（均P〈0．05）。结论沙利度胺能降低移植动脉TNF-α及PCNA蛋白的表达,缓解移植动脉的纤维化进程以及内膜增生,对慢性排斥反应所致的移植物血管病具有抑制作用。     

强精片对弱精子症SD大鼠MAPK通路的影响研究

目的:观察强精片对弱精子症SD大鼠精液质量及MAPK通路的影响。方法:选取100只SD大鼠,采用单纯随机抽样方法分为空白对照组、模型组、强精片高剂量组、强精片中剂量组、强精片低剂量组,每组20只。除空白对照组外各组大鼠皆予奥硝唑(ORN)200 mg/(kg·d)灌胃造模,空白对照组大鼠1%羧甲基纤维素钠溶液1ml/100g灌胃,高剂量组、中剂量组、低剂量组均在灌胃ORN的同时,予不同剂量强精片:6 700 mg/(kg·d)、3 300 mg/(kg·d)、1 700 mg/(kg·d),每周给药6 d,1次/d,连续20 d。实验结束后予电镜观察睾丸组织、细胞凋亡情况,采用S-P法测定睾丸波形蛋白表达,Western印迹测定大鼠睾丸ERK1/2表达,ELISA法检测精液中TGF-β1表达量测定。结果:(1)电镜结果显示模型组大鼠睾丸精母细胞,细胞核呈圆形,染色质分布均匀,胞浆内,线粒体的脊断裂或消失、严重肿胀,粗面内质网扩张;与模型组相比,高剂量组、中剂量组、低剂量组大鼠睾丸精母细胞,细胞核呈圆形,染色质分布均匀,胞浆内,线粒体,粗面内质网,核糖体等细胞器结构清晰,均与对照组类似。(2)空白对照组、模型组、高剂量组、中剂量组、低剂量组ERK1/2、波形蛋白相对表达量、睾丸组织细胞凋亡率(%)、精液TGF-β1表达量(ng/ml)分别为(1.00±0.00)、(1.26±0.10)、(1.14±0.08)、(1.18±0.05)、(1.19±0.19),(0.16±0.01)、(0.17±0.01)、(0.16±0.01)、(0.17±0.09)、(0.17±0.00),(9.20±3.07)、(42.20±9.17)、(21.60±5.94)、(33.95±6.39)、(40.85±5.61),(627.67±26.07)、(566.73±68.44)、(621.78±30.80)、(583.93±44.24)、(587.69±59.29)。模型组睾丸组织内ERK1/2、波形蛋白表达量高于对照组(P0.01),模型组大鼠睾丸组织凋亡阳性细胞率较对照组明显升高(P≤0.01),而精液中TGF-β1表达量低于空白对照组(P≤0.05);与模型组相比,高剂量组ERK1/2表达量、波形蛋白表达量均明显降低(P0.01),中剂量组ERK1/2表达量、波形蛋白表达量均降低(P0.05),高剂量组大鼠睾丸组织凋亡阳性细胞率明显降低(P≤0.01),中剂量组大鼠睾丸组织凋亡阳性细胞率降低(P≤0.05),而高剂量组精液中TGF-β1表达量明显高于模型组(P0.05)。结论:强精片可能是通过抗氧化应激改善弱精子症大鼠的精子质量。     

IgA大鼠肾组织中TGF-β_1的表达与肾损害关联性研究

目的:检测IgA肾病大鼠血清尿液中转化生长因子-β_1(transforming growth factor beta-1,TGF-β_1)的含量和肾组织中TGF-β_1表达水平,探讨TGF-β_1体内表达与肾损害程度的关联性。方法:将60只SD大鼠随机分为3组,每组20只,以牛血清白蛋白(bovine serum albumin,BSA)灌胃剂量不同分为正常对照组,低剂量组(400 mg/kg),高剂量组(600 mg/kg),各组接受相应的建模干预处理。建模后第8周、12周每组各处死10只大鼠,留取血、尿、肾组织标本检测。酶联免疫吸附法(ELISA)测血清尿液TGF-β_1的含量,免疫组织化学法测TGF-β_1在各组肾组织中的表达。结果:第8、12周时,高剂量组尿液中TGF-β_1的含量和肾组织中MPC-1表达明显高于低剂量组(P0.05),高剂量组血肌酐、尿素氮及24 h尿蛋白定量明显高于低剂量组,高剂量组间质损害的评分高于低剂量组。三组间血清TGF-β_1的含量差异无统计学意义(P0.05)。结论:高剂量BSA灌胃可增加IgA肾病大鼠尿液TGF-β_1含量和肾组织中表达,随着尿液TGF-β_1含量和肾组织中TGF-β_1表达水平的增加,肾脏损害程度加重,提示TGF-β_1可作为肾脏损害检测指标。     

伊马替尼抑制大鼠静脉移植物内膜增生

目的 观察伊马替尼对自体移植静脉内膜增生的影响.方法 建立大鼠自体颈外静脉移植模型,实验分为4组:移植组、低剂量给药组、高剂量给药组及对照组.移植4周后取移植静脉,行病理学检查观察内膜增生情况,免疫组织化学及Western blot法检测PDGFRβ、ERK及P-PDGFRβ、P-ERK蛋白表达情况.结果与对照组比较,移植组和低剂量给药组内皮下平滑肌细胞大量增生,静脉内膜显著增厚,管腔明显狭窄,高剂量给药组内膜无明显增厚.Western blot结果显示,移植组血管P-PDGFRβ蛋白含量(P-PDGFRβ/GAPDH)较对照组明显增加(0.81±0.06比0.18±0.02,P<0.05),而高剂量给药组较移植组明显减少(0.32±0.03比0.81±0.06,P<0.05),低剂量给药组与移植组比较差异无统计学意义(P>0.05),P-ERK蛋白表达亦呈同样趋势变化.结论 高剂量伊马替尼能有效抑制自体移植静脉内膜增生,其机制可能与抑制PDGF信号通路蛋白磷酸化,从而抑制平滑肌细胞增殖有关.     

输注供鼠骨髓间充质干细胞延长肾移植大鼠的存活时间

目的 探讨在同种大鼠肾移植中输注供者骨髓间充质干细胞(MSC)对急性排斥反应的影响以及延长受鼠存活时间的作用.方法 取Wistar大鼠骨髓,分离和培养其MSC.以Wistar 大鼠为供者,Lewis大鼠为受者,建立同种大鼠肾移植模型.根据受鼠处理方式的不同,分为低剂量MSC组、高剂量MSC组、CsA组及对照组,低剂量MSC组和高剂量MSC组于移植前后分别多次输注1×106个和t×107个供者MSC,CsA组于术后2d开始腹腔内注入CsA 0.5 mg·kg-1 ·d-1,以腹腔内注射PBS作为对照.移植后,比较各组受鼠的存活时间,观察各组移植肾功能及移植肾组织病理学改变.结果 低剂量MSC组、高剂量MSC组、CsA组及对照组受鼠的存活时间分别为(21.7±7.2)d、(31.2±14.3)d、(34.9±15.7)d及(9.0±2.3)d;低剂量MSC组、高剂量MSC组和CsA组存活时间均明显长于对照组(P＜0.01),而低剂量MSC组存活时间明显短于高剂量MSC组和CsA组(P＜0.05).术后第4天,高剂量MSC组和CsA组移植肾组织形态和结构基本正常;对照组移植肾组织则表现出典型的急性排斥反应,出现广泛间质性浸润,肾小管炎症和片状坏死、出血,肾小球炎症浸润严重;而与对照组相比,低剂量MSC组急性排斥反应的病理表现则要明显减轻.结论 同种肾移植大鼠输注供者MSC后,可以达到有效的免疫调节作用,并且可明显延长大鼠的存活时间,呈MSC剂量依赖性.     

缬沙坦对大鼠气管移植物局部纤维化及缺氧诱导因子表达的抑制作用

目的 研究缬沙坦对大鼠异位气管移植物局部纤维化和气道闭塞的抑制作用及其对缺氧诱导因子表达的影响.方法 建立大鼠同种异体异位气管移植模型,实验随机分为3组.(1)同系移植对照组:供、受者均为SD大鼠,受者气管移植后不作任何处理.(2)同种移植对照组:供者为Wister大鼠,受者为SD大鼠,受者气管移植后仅给予质量分数为0.5%的羧甲基纤维素钠溶液和生理盐水灌胃.(3)同种移植实验组;供者为Wister大鼠,受者为SD大鼠,受者气管移植前第1天至术后第28天给予缬沙坦60 mg·kg-1·d-1,用质量分数为0.5%的羧甲基纤维素钠溶液配成6 g/L的悬液,每天分两次灌胃给予.移植后第28天处死受者,并取出移植物进行病理学、免疫组织化学及原位杂交法检测.结果 两个同种移植组气管移植物均可观察到各种程度类似于闭塞性细支气管炎的病理改变.同种移植实验组和同种移植对照组移植物局部纤维化程度分别为(65.94±17.05)%和(91.55±12.15)%;I型胶原表达指数分别为2.08±0.22和4.51±0.48;Ⅲ型胶原表达指数分别为3.46±0.42和10.60±1.26;缺氧诱导因子-1α(HIF-1α)表达指数分别为7.62±0.59和9.34±0.62;转化生长因子p(TGF-β)表达指数分别为3.98±0.42和12.86±0.96;结缔组织生长因子(CIGF)表达指数分别为6.65±0.52和11.83±0.96.同种移植实验组各项表达明显受到抑制(P＜0.001).结论 缬沙坦在大鼠异位气管移植模型中可能通过抑制缺氧诱导因子的表达而抑制了闭塞性细支气管炎的进展.     

大鼠肝移植排斥反应时γ干扰素及白细胞介素10的表达及意义

目的 探讨大鼠肝移植排斥反应时γ干扰素(IFN-γ)及白细胞介素10(IL-10)的表达及意义.方法 采用改良的Kamada"二袖套法"制备大鼠原位肝移植模型,同系移植组供、受者均为SD大鼠;同种异体移植组的供者为Wistar大鼠,受者为SD大鼠;另设假手术组.术后7 d处死动物,观察移植肝脏的组织学变化,检测血清IFN-γ和IL-10的含量,以及移植肝脏内IFN-γ和IL-10 mRNA的表达.结果 同种异体移植组移植肝脏有较多坏死肝细胞,汇管区及中央静脉周围可见以淋巴细胞为主的炎症细胞浸润,胆管上皮细胞可见胞浆空泡变性、核固缩或碎裂,整个肝小叶结构紊乱.同系移植组肝脏组织结构仅有轻度缺血再灌注损伤表现,汇管区有较少炎症细胞浸润,胆管上皮细胞结构和肝小叶结构基本正常.同种异体移植组血清IFN-γ为(386.7±14.4)Pg/ml,明显高于同系移植组的(159.8±16.5)pg/ml(P<0.05);同种异体移植组血清IL-10为(126.3±13.1)pg/ml,明显低于同系移植组的(288.3±17.1)pg/ml(P<0.05).同种异体移植组移植肝组织内IF-γ mRNA表达水平明显高于同系移植组(P<0.05),而IL-10 rnRNA表达水平明显低于同系移植组(P<0.05).结论 大鼠肝移植排斥反应时IFN-γ表达明显升高,IL-10表达明显降低;T_H1/T_H2型细胞因子的动态平衡可能在大鼠肝移植排斥反应中起着重要作用.     

应用吡格列酮抑制大鼠血管移植物慢性病变

目的 研究吡格列酮对血管移植物慢性病变的影响,并探讨其作用机理.方法 制备大鼠腹主动脉移植模型.实验组以Wistar大鼠为供者,SD大鼠为受者,进行腹主动脉移植,术后采用吡格列酮(0.04 g/kg)灌胃8周;同种移植对照组以Wistar大鼠为供者,SD大鼠为受者,进行腹主动脉移植.术后采用牛理盐水灌胃8周;同系移植对照组的供、受者均为SD大鼠,术后采用生理盐水灌胃8周.移植后第8周,取移植腹主动脉段,行HE染色,显微镜F观察组织形态学变化,测量内膜厚度与中膜厚度的比值;采用免疫组织化学法测定移植动脉绀织中细胞问粘附分子-1(ICAM-1)的表达;采用双抗体夹心酶联免疫吸附试验检测血清血小板衍生生长因子(PDGF)浓度.结果 移植后第8周,同系移植对照组的血管内膜无明显变化,同种移植对照组和实验组移植血管组织均呈现出典型的移植相关血管硬化,内膜呈弥漫性向心性显著增生,管腔狭窄,新生内膜见较多血管平滑肌细胞增生,大量成纤维细胞增生,内膜可见少量单核细胞浸润;中膜变薄,内弹力纤维有断裂;外膜见大量单个核细胞,同种移植对照组的病理改变较实验组更加明显.同种移植对照组内膜厚度/中膜厚度比值为1.4140±0.2232,实验组为0.4010±0.0910,二者比较,差异有统计学意义(P＜0.01).同种移植对照组ICAM-1阳性细胞数为(26.114±1.493)个,实验组为(8.943±1.061)个,二者比较,差异有统计学意义(P＜0.01).同种移植对照组的血清PDGF含量为(1023±27)pg/ml,实验组为(265±100)pg/ml,二者比较,差异有统计学意义(P＜0.01).结论 吡格列酮能够延缓移植动脉慢性血管病变的发展,这种作用可能与局部ICAM-1表达下调、血清PDGF浓度下降有关.     

基于腺性膀胱炎模型大鼠探讨八正散对IL-6、IL-17、TGF-β_1表达的影响

目的探讨八正散对腺性膀胱炎病理模型大鼠相关细胞因子的影响机制。方法以腺性膀胱炎模型大鼠为研究对象,随机分为空白组、模型组、对照组和八正散的不同剂量(高、中、低)组。对照组给予羟基喜树碱每天3mg/kg膀胱灌注,八正散高、中、低剂量组分别给予同体积八正散液(生药浓度分别为0.84g/mL、0.42g/mL、0.2lg/mL),每日2次,灌注/灌胃连续2周。HE染色观察膀胱病理变化,免疫组织化学法观察膀胱组织中的白细胞介素6(interleukin6,IL-6)、白细胞介素17(interleukin17,IL17)、转化生长因子β_1(Transforming growth factor-β_1,TGF-β_1)的表达。结果对照组及八正散高剂量组大鼠膀胱黏膜固有层炎细胞浸润、间质水肿、局灶性坏死和黏膜固有层内Brunn巢及腺上皮化生等较模型组明显减少。与空白组比较,模型组的IL-6、IL-17和TGF-β_1的含量显著升高,差异有统计学意义(P0.01);与模型组比较,对照组及高剂量八正散组IL-6、IL-17和TGF-β_1的含量显著降低,差异有统计学意义(P0.05)。中剂量组1L-6、TGF-β_1的含量显著降低,差异有统计学意义(P0.05)。结论八正散可以有效改善腺性膀胱炎模型大鼠膀胱病变程度,推测与下调IL-6、IL-17和TGF-β_1含量有关。     

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.     

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.