肺泡巨噬细胞Toll样受体4在肝脏缺血再灌注损伤小鼠肺组织中的表达及意义

目的 探讨肺泡巨噬细胞Toll样受体4在肝脏缺血再灌注损伤小鼠肺组织中的表达及意义.方法 以野生型小鼠C3h/Heouj及TLR4缺失小鼠C3h/Hej复制全肝脏缺血再灌注损伤模型,分别于缺血20 min再灌注1 h,6 h时经支气管肺泡灌洗(bronchoalveolar lavage fluid,BALF)获取肺泡巨噬细胞和肺泡灌洗液,采用免疫组织化学法检测肺泡巨噬细胞表面TLR4的表达,并以鲎试剂内毒素检测试剂盒和酶联免疫吸附试验(ELISA)检测灌洗液中内毒素及肿瘤坏死因子-α(TNF-α)的水平.同时检测肺组织湿/干重比值、肺组织髓过氧化物酶(myeloperosidase,MPO)的含量以及计算肺组织学评分.结果 (1)与假手术组小鼠相比,野生型小鼠(C3h/Heouj)在缺血再灌后各时间点肺泡巨噬细胞Toll样受体4蛋白表达升高,6 h强于1 h,且支气管肺泡灌洗液中TNF-α的水平明显升高,肺组织湿/干重比值持续升高,MPO的含量持续增加(P＜0.05).(2)与C3h/Heouj小鼠相比,C3h/Hq组小鼠在再灌注后支气管肺泡灌洗液中TNF-α的含量明显降低(P＜0.05),肺损伤明显减轻(P＜0.05),肺组织湿/干重比值及MPO的含量明显下降(P＜0.05).(3)各组小鼠缺血再灌注后1 h肺泡灌洗液中内毒素水平与假手术组相比,差异无统计学意义(P＜0.05),而在6 h时则明显升高,差异有统计学意义(P＜0.05).结论 小鼠全肝缺血再灌注过程中,肺泡巨噬细胞表面Toll样受体4激活,并与肺功能损伤有关.     

小鼠全肝缺血再灌注时肺泡巨噬细胞TLR2的激活与肺损伤的机制

目的：探讨肺泡巨噬细胞Toll样受体2（TLR2）的激活机制及其在肝脏缺血再灌注（HIR）中肺损伤的意义。方法：用野生型小鼠C3h/Heouj和TLR4缺失小鼠C3h/Hej建立HIR动物模型。于再灌注1，6，12h后经支气管肺泡灌洗液获取肺泡巨噬细胞，采用荧光定量PCR方法检测TLR2/4mRNA的表达。同时检测支气管肺泡灌洗液中内毒素及肿瘤坏死因子（TNF）的水平，肺组织湿干重比值，肺组织髓过氧化物酶的浓度，并进行肺组织学评分。结果：C3h/Heouj组HIR缺血再灌后各时点肺泡巨噬细胞TLR2/4mRNA表达升高，TLR2mRNA表达持续升高，TLR4mRNA6h达到最高值。同时C3h/Heouj组HIR后支气管肺泡灌洗液中TNF水平明显升高，肺损伤加重，肺组织湿干重比值持续升高，肺组织髓过氧化物酶持续增加(P<0.05)。C3h/Hej组HIR后TLR2mRNA表达仅轻度升高，且支气管肺泡灌洗液中TNF水平低于C3h/Heouj组(P<0.05)，肺损伤轻于C3h/Heouj组(P<0.05)。结论：HIR可致肺泡巨噬细胞表面TLR4的激活，可上调TLR2的表达，从而可加重HIR时的肺损伤。     

地塞米松治疗急性坏死性胰腺炎的实验研究

目的探讨地塞米松治疗急性坏死性胰腺炎(ANP)的机理.方法经胰胆管逆行注射牛磺胆酸钠法诱导SD大鼠ANP,治疗组(n=24)模型诱导30 min后注射地塞米松0.2 mg/100 g鼠重,对照组(n=24)注射等量生理盐水,两组分别于4 h和12 h各处死8只鼠测血清肿瘤坏死因子α(TNFα)、淀粉酶,并行胰腺坏死程度评分、检测胰腺腺胞细胞凋亡,余下8只鼠作生存期观察.结果治疗组4 h、12 h TNFα分别为(17.8±2.7) pg/ml和(8.5±1.6) pg/ml,胰腺腺胞细胞凋亡指数分别为(36.94±4.12)%和(32.79±3.31)%,生存时间为(33.4±21.5) h; 对照组上述各项指标依次为(53.6±18.7) pg/ml和(37.2±11.1) pg/ml (P<0.01)、(4.37±1.24)%和(5.12±2.11)%(P<0.01)及(14.6±5.7) h (P<0.01),两组胰腺坏死程度评分差异有显著性意义(P<0.01).结论地塞米松能通过抑制TNFα调控细胞凋亡,细胞凋亡对胰腺具有保护作用.     

丙氨酰-谷氨酰胺二肽保护大鼠肝脏缺血再灌注损伤的实验研究

目的探讨丙氨酰-谷氨酰胺二肽(Ala-Gln)对肝脏缺血再灌注损伤(HIRI)的保护作用.方法采用大鼠HIRI模型(Pringle's法阻断入肝血流30 min),分谷氨酰胺组(G组)及对照组(C组),检测再灌注后血清肝生化酶、肝组织还原型谷胱甘肽(GSH)及超氧化物歧化酶(SOD)水平,对肝组织进行光镜与电镜检查,并计算术后24 h生存率.结果再灌注1h,G组血清ALT(499.25±120.84)U/L、LDH(6 956.00±2 443.93)U/L的水平均显著低于C组(ALT823.56±328.71,P<0.05;LDH11 715.31±2 993.50,P<0.01);再灌注24 h,两组血清ALT、LDH的水平均有显著恢复,但G组(ALT176.69±151.84;LDH415.38±213.68)水平仍显著低于C组(ALT548.25±257.25;LDH1 958.50±687.32;P<0.01).再灌注1 h及24 h,G组GSH的水平分别为(1 216.09±152.78)μg·g-1·p、(899.73±57.75)μg·g-1·p,均明显高于C组(分别为856.68±117.64,P<0.01;800.50±94.79,P<0.05);两组SOD的活性无统计学差异.G组肝脏组织学与细胞学损害均明显轻于C组.G组术后24h生存率为78.57%(11/14),明显高于C组的45.45%(10/22)(P<0.05).结论 Ala-Gln(Gln)对HIRI具有保护作用,而这种保护作用部分是通过维持肝脏组织中GSH的含量来介导的.     

RNA干扰Kupffer细胞肿瘤坏死因子-α减轻大鼠肝脏缺血再灌注损伤

目的 观察RNA干扰肝脏Kupffer细胞肿瘤坏死因子-α(TNF-α)对大鼠肝脏缺血再灌注损伤的保护作用.方法 构建针对大鼠TNF-α基因的短发夹状RNA(shRNA)真核表达载体.肝脏缺血再灌注损伤前48 h经门静脉注射磷酸盐缓冲液(PBS)、空载体或TNF-α shRNA.实验随机分为4组,假手术组、PBS组、空载体组和shRNA组.阻断大鼠70%入肝血流40 min,再灌注6 h检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、肝脏Kupffer细胞TNF-α mRNA、血清TNF-α、肝组织中丙二醛(MDA)以及超氧化物岐化酶(SOD)含量.结果 与PBS组和空载体组比较,shRNA组再灌注6 h后血清ALT和AST水平显著降低(P＜0.05),Kupffer细胞TNF-α mRNA水平、血清TNF-α水平(56.6±6.7 pg/ml比87.8±8.7 pg/ml和96.5±7.3 pg/ml,P＜0.05)、肝组织中MDA含量(93.4±13.3 nmol/mg比133.5±12.4 nmo1/mg和136.7±13.6 nmol/mg,P＜0.05)显著降低,SOD活性显著升高(22.4±4.6 U/mg比12.2±3.1 U/mg和11.4±2.9 U/mg,P＜0.05).结论 RNA干扰Kupffer细胞TNF-α基因的表达可以减轻大鼠肝脏缺血再灌注损伤.     

氯化钆对肝脏缺血再灌注损伤中缺血肝叶Toll样受体2表达的影响

目的观察氯化钆(GdCl_3)对小鼠肝脏部分缺血再灌注损伤模型中缺血肝叶Toll样受体2(TLR2)表达的影响,探讨枯否细胞(KC)参与肝脏缺血再灌注损伤的机制。方法实验小鼠(BALB/C)被分成氯化钆阻断组、非氯化钆阻断组和假手术组等3组。采用免疫组织化学法观察KC和TLR2阳性细胞的分布并分析两者的相关性。实时逆转录-聚合酶链反应(RT-PCR)法定量检测缺血肝叶中TLR2 mRNA的表达。并检测门静脉血浆丙氨酸氨基转移酶(pALT)、肿瘤坏死因子(TNF)-a水平。结果氯化钆阻断组小鼠肝脏KC被抑制,即缺血肝叶CD68染色阳性率下降(32．97±10．55 vs 185．65±21．88,P＜0．01),TLR2阳性细胞明显低于非氯化钆阻断组(75．74±17．44 vs 170．58±25．14,P＜0．01)),且CD68细胞变化与TLR2阳性细胞变化高度相关(r= 0．945,P＜0．01)。氯化钆阻断组小鼠缺血肝叶TLR2 mRNA表达明显低于非氯化钆阻断组(△Ct值：4．02±1．22 vs 1．05±1．02,P＜0．01,△Ct值越大表明基因表达水平越低),但均高于假手术组(act值：1．05±1．02,4．02±1．22．vs 5．08±1．36,P＜0．05)；门静脉血清TNF-a和pALT水平水平较非氯化钆阻断组下降[TNF-a：(84．45±14．73)ng/L vs(112．32±17．56)ng/L,P＜0．05；pALT：(435．89±78．37)U/L vs(890．21±272．91)U/L,P＜0．01],但均高于假手术组(P＜0．01)。结论在肝脏缺血再灌注损伤过程中,氯化钆可能通过抑制小鼠肝脏KC中TLR2的表达,降低KC分泌TNF-a而减轻肝功能损伤。     

小鼠肝缺血再灌注后Toll样受体2在缺血肝组织中的激活及其意义

目的　探索小鼠肝缺血再灌注后缺血肝组织中Toll样受体 2 (TLR2 )的激活及其与肝功能损伤之间的关系。方法　缺血再灌注损伤组 (I/R组 ),假手术对照组 (S组 )均采用实时荧光定量多聚酶链反应检测肝组织中TLR2mRNA及TLR2蛋白的表达,同时检测门静脉血浆丙氨酸氨基转移酶(ALT)、肿瘤坏死因子α(TNF α)及门静脉血清内毒素 (endotoxin, EN)水平。结果　肝脏部分缺血1h再灌注 4h后,I/R组与S组小鼠缺血肝组织TLR2 mRNA的表达 (ΔCt值 )分别为 1. 0 6±0. 9 1和5. 0 8±1. 3 2, 两组间差异有显著性 (P < 0. 0 1 ),I/R组缺血肝组织TLR2 蛋白的表达 (OD值 )( 4 3 3. 9 1±2 5. 5 3 )水平较S组 ( 1 0 2. 8 6±1 3. 5 8 )显著升高 (P< 0. 0 1 )。I/R组门静脉血清TNF α[ ( 1 1 2. 5 2±1 4. 4 1 )pg/mL]较S组 [ ( 5. 9 6 ±4. 4 3 )pg/mL]显著升高 (P < 0. 0 1 );I/R组ALT[ ( 8 4 8. 3 3±2 7 1. 3 7 )U/L]较S组 [ ( 4 2. 3 9±1 4. 7 5 )U/L]显著升高 (P < 0. 0 1 );而门静脉血清内毒素水平组间差异无显著性 (P> 0. 0 5 )。结论　TLR2mRNA及蛋白在肝脏缺血再灌注过程中缺血肝组织的表达增强, 此变化伴有TNF α的升高及肝功能的损伤。     

氯喹在小鼠肝脏热缺血-再灌注损伤中的保护作用

目的:研究氯喹对小鼠肝脏热缺血-再灌注损伤的保护作用,并探讨相关机制。方法:Balb/c小鼠建立肝脏部分热缺血-再灌注模型。氯喹组给予氯喹预处理,对照组给予等体积生理盐水。肝脏再灌注1、6、24 h后检测血清谷氨酸转氨酶(ALT)水平,HE染色检测肝脏病理学变化,荧光定量PCR检测炎症因子TNF-α和IL-6 m RNA水平,Western印迹检测肝脏TLR4及HMGB1表达。结果 :与对照组相比,氯喹组再灌注1、6、24 h血清ALT显著下降(P<0.05);肝细胞变性坏死、炎性细胞浸润显著减轻(P<0.01);血清TNF-α、IL-6含量显著降低(P     

异氟醚预处理对大鼠肝脏缺血再灌注损伤的影响

目的 探讨异氟醚预处理对大鼠肝脏缺血再灌注损伤的影响.方法 成年雄性SD大鼠24只,体重180～220 g,随机分为3组(n=8):假手术组(S组)吸人纯氧30 min,间隔30 min后仅开腹;肝脏缺血再灌注组(IR组)吸入纯氧30 min,间隔30 min后行肝脏缺血60 min,再灌注4 h;异氟醚预处理组(Iso组)吸入1.4%异氟醚30 min,间隔30 min后行肝脏缺血60 min,再灌注4 h.于再灌注4 h时处死大鼠,留取肝脏及腹主动脉血5ml.测定血清谷丙转氨酶(ALT)和谷草转氨酶(AST)浓度,血清及肝组织匀浆上清液中肿瘤坏死因子α(TNF-α)的浓度,肝组织髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量,观察肝组织病理学改变.结果 与S组比较,IR组、Iso组血清ALT、AST和TNF-α水平明显升高,肝组织TNF-α含量升高,肝组织MPO活性升高,MDA含量升高,SOD活性降低(P＜0.05或0.01),肝组织病理损伤明显;与IR组比较,Iso组血清ALT、AST和TNF-α水平降低,肝组织TNF-α含量降低,肝组织MPO活性降低,MDA含量降低,SOD活性升高(P＜0.05或0.01),肝组织病理损伤程度减轻.结论 1.4%异氟醚预处理可明显减轻大鼠肝脏缺血再灌注损伤,其机制可能与抑制TNF-α的释放、减少中性粒细胞在肝组织的浸润有关.     

CO2气腹对荷瘤大鼠IL-1β、IL-6和腹膜巨噬细胞功能的影响

目的采用种植性大鼠肝脏肿瘤模型观察CO2气腹对细胞因子和腹膜巨噬细胞功能的影响.方法荷瘤大鼠32只随机分为4组(n=8)对照组(仅麻醉)、开腹组、免气腹组和CO2气腹组.术后2、24 h收集血清,检测血清中的IL-1β、IL-6水平;术后48 h,收集培养腹膜巨噬细胞,检测巨噬细胞产生的TNF-α水平.结果术后2、24 h开腹组IL-6的水平分别为(57.92±2.06)pg/ml,(35.49±1.15)pg/ml,显著高于CO2气腹组(14.64±0.34)pg/ml,(15.39±0.86)pg/ml,免气腹组(24.75±1.53)pg/ml,(17.10±0.97)pg/ml和对照组(17.75±1.60)pg/ml,(14.55±0.25)pg/ml(P＜0.05).术后2 h开腹组IL-1β的水平为(92.63±4.81)pg/ml,显著高于CO2气腹组(57.94±4.46)pg/ml、免气腹组(58.48±3.20)pg/ml和对照组(58.99±2.30)pg/ml(P＜0.05).CO2气腹组腹膜巨噬细胞产生的TNF-α水平为(35.69±3.54)pg/ml,显著低于免气腹组(68.87±4.08)pg/ml、开腹组(82.96±5.39)pg/ml和对照组(66.45±7.96)pg/ml(P＜0.05).结论腹腔镜术后机体应激反应较小,CO2气腹可能抑制腹膜巨噬细胞的功能.     

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.     

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.     

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.