缺血预处理对大鼠肝脏低温保存损伤的保护作用

目的　探讨缺血预处理 (IPC)对大鼠肝脏低温保存损伤的保护作用。方法　制备大鼠肝脏离体非循环灌注模型 ,对供肝分别作不同时间的IPC (IPC1组缺血 5min、IPC2 组缺血 10min、IPC3 组缺血 15min) ,而后比较各组供肝的损伤程度。结果　流出液中AST和ALT的水平 ,IPC1组分别为 (4 0 .1± 6.3 )U/L和 (17.1± 0 .5 )U /L ,IPC2 组分别为 (5 3 .6± 3 .7)U/L和 (19.7± 0 .5 )U /L ,均显著低于未预处理 (NPC)组的 (64 .5± 8.2 )U/L和 (2 3 .8± 3 .9)U /L (P<0 .0 5 ) ;IPC1组又显著低于IPC2 组和IPC3 组的 (63 .8± 7.2 )U/L和 (2 2 .8± 2 .5 )U /L (P<0 .0 5 )。LDH水平 ,NPC组、IPC1组、IPC2 组和IPC3 组分别为 (10 4.3± 2 0 .6)U/L、(84.1± 19.7)U /L、(90 .5± 2 1.1)U/L和 (10 3 .1± 18.5 )U /L ,4组间差异无统计学意义 (P>0 .0 5 ) ,但均高于正常组〔(71.5± 18.9)U /L〕 (P<0 .0 5 )。胆汁分泌量及肝组织ATP含量 ,IPC1组分别为 (5 3 .5± 10 .2 ) μl和 (6.15± 0 .65 ) μmol/g ,IPC2 组分别为 (4 1.5± 8.1) μl和 (4 .77± 0 .2 1) μmol/g ,均显著高于NPC组的 (2 2 .8± 9.7) μl和 (2 .62± 0 .3 4) μmol/g (P<0 .0 5 ) ;IPC1组又显著高于IPC2 组和IPC3 组的 (2 7.5± 2 .8) μl和 (2 .61     

一氧化氮对岛状肌皮瓣缺血再灌注损伤的影响

目的　观察NO对岛状肌皮瓣I/R损伤的影响并探讨其作用机制。方法　选用白色小家猪 15只 ,随机分为I/R组、I/R +NO供体L -arg组及对照组。制作猪腹直肌岛状肌皮瓣I/R模型 ,于再灌注前后给予L -arg ,检测I/R不同时相皮瓣静脉血中NO的间接含量、皮瓣NTR渗出 ,计算再灌注完毕后肌肉存活比例。结果　①I/R +L -arg组再灌注 0 .5小时、1小时NO间接含量 ( 75 .0 7± 12 .5 4 ) μmol/L、( 86.86± 2 0 .15 ) μmol/L ,明显高于I/R组 ( 4 6.75± 11.77) μmol/L、( 4 0 .3 8± 10 .78) μmol/L(P <0 .0 1)。②再灌注 1小时、4小时I/R +L -arg组皮瓣NTR计数 ( 66.5 0± 17.3 3～ 15 3 .80± 3 8.5 3 ) / 2 0个高倍视野明显低于I/R组 ( 171.5 0± 4 4 .5 0 ,3 16.80± 5 2 .85 ) / 2 0个高倍视野 (P <0 .0 1)。③再灌注完毕后 ,I/R +L -arg组皮瓣肌肉的存活比例 ( 83 .70± 15 .60 ) %明显高于I/R组 ( 2 4 .0 7± 12 .3 5 ) % (P <0 .0 1)。结论　于缺血后再灌注前及再灌注早期给予L -arg ,适当增加内源性NO的产生 ,能有效减轻肌皮瓣缺血再灌注损伤。     

肾上腺髓质素心肌保护作用机制的实验研究

目的　探讨肾上腺髓质素 (Adm1 5 0 )对缺血再灌注大鼠心肌组织血管细胞粘附分子 1(VCAM 1)表达的影响。方法　 2 4只雄性SD大鼠 ,制作离体心脏缺血再灌注模型 ,并随机分为A、B、C、D4组 ,每组 6只。心脏缺血 6 0min ,A组用氧合K H液再灌注 6 0min ,B、C、D组用氧合K H液分别加入10 -9mol/L、10 -8mol/L、10 -7mol/L的Adm1 5 0再灌注 15min ,再用K H液灌注 45min。逆转录 -聚合酶链式反应 (RT PCR)法检测心肌组织VCAM 1mRNA表达 ,并测定磷酸肌酸激酶同工酶 (CK MB)释放。结果　Adm1 5 0抑制再灌注大鼠心肌组织VCAM 1表达的作用呈浓度依赖性。Adm1 5 0减少了再灌注末心肌组织CK MB漏出量 ,A组 ( 31 5± 3 3)U/L、B组 ( 2 9 7± 3 3)U/L、C组 ( 2 4 3± 3 0 )U/L、D组 ( 19 3± 3 2 )U/L ,C、D组与A组比较P <0 0 1。结论　心肌缺血再灌注时 ,Adm1 5 0通过抑制VCAM 1mRNA表达而产生心肌保护作用。     

缺血预处理对大鼠移植肝脏保存再灌注损伤的保护及机制探讨

目的探讨缺血预处理 (ischemicpreconditioning ,IP)对大鼠移植肝脏保存再灌注损伤的保护作用及机理。方法采用SD大鼠原位肝移植动物模型 ,12 8只大鼠随机分成A(对照组 )、B(IP组 )、C(腺苷 ,Ado组 )、D(NO合成抑制剂 ,NAME组 )组 ,每组 32只。其中各组的半数用于观察存活率 ,另一半用于移植肝脏再灌注 2h后取血及肝脏检测。结果IP组和Ado组的 1周存活率、血清NO水平及肝组织腺苷含量分别为 88% (7/ 8)和 88% (7/ 8) ,(33 0± 6 1) μmol/l和 (2 9 1± 6 5 ) μmol/l,(7 2± 1 8) μmol/g和 (5 7± 1 3) μmol/g ,均高于对照组的 38% (3/ 8) ,(15 4± 3 0 )mol/L和 (3 6 9±0 5 4 ) μmol/g (P <0 0 5 ) ,血清ALT及TNF含量分别为 (2 87± 82 )IU/L和 (35 7± 93)IU/L ,(1 15± 0 2 3)ng/ml和 (1 14± 0 2 7)ng/ml,均低于对照组的 (5 88± 5 8)IU/L及 (1 5 9± 0 35 )ng/ml(P <0 0 5 ) ,组织的病理学改变也轻于对照组 ;NAME组的 1周存活率、血清NO及ALT含量等分别为 2 5 % (2 / 8)、(13 74± 3 11) μmol/l及 (6 34± 6 5 )IU/L ,与对照组相近 (P >0 0 5 ) ,而肝组织腺苷含量为 (5 5 6± 1 19)μmol/g ,与对照组差异有显著意义 (P <0 0 5 )。 结论IP对大鼠移植肝脏的保存再灌注损伤具有保护     

高能灌注液对骨骼肌缺血保护作用的研究

目的探讨高能灌注液对缺血再灌注骨骼肌的保护作用.方法选用健康新西兰大白兔30只,建立左后肢缺血模型.根据灌注液的不同将30只大白兔平分为对照组、ATP-MgCl2组、高能灌注液组.实验结束后测量左右胫前肌的最大强直收缩张力、抽取左侧股静脉血测定血清CK、LDH;取左胫前肌标本分别作骨骼肌肌细胞ATP测定.结果高能灌注液组左右胫前肌最大强直收缩张力之比为0.8275±0.0430(±s,下同)、肌细胞ATP为(0.4847±0.0317)μmol/g、血清CK、LDH分别为(6285.2±1464.9)U/L和(463.7±48.0)U/L,较其它两组有明显改善.结论高能灌注液能够有效地保护缺血再灌注骨骼肌;从骨骼肌缺血再灌注损伤机制的不同环节进行多种药物联合应用是减轻骨骼肌缺血再灌注损伤较为有效的方法.     

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。     

丹参对大鼠肝脏低温保存损伤的保护作用

目的　研究丹参对大鼠肝脏低温保存损伤的保护作用。方法　采用大鼠肝脏离体非循环灌注模型 ,观察乳酸林格液 (LR液 )中加入不同剂量丹参后保存大鼠肝脏 1 2h的效果。结果　丹参组 ( 60 0mg/g)肝组织ATP含量 ( 6.0 8± 0 .67) μmol/g及分泌胆汁量 ( 1 0 5.6± 1 2 .4) μl/h明显高于对照组 ( 2 .52± 0 .31 ) μmol/g及 ( 57.4± 8.2 ) μl/h(P <0 .0 5) ,丹参组 ( 60 0mg/g)肝组织 2 ,3 二羟苯甲酸 ( 2 ,3 DHBA) ( 0 .1 54± 0 .0 1 3)nmol/g、2 ,5 DHBA( 1 .354± 0 .0 68)nmol/g及流出液天门冬氨酸转氨酶 (AST) ( 38.4± 3.7)U/L明显低于对照组 ( 0 .2 4 5± 0 .0 2 1 )nmol/g、( 2 .1 0 5± 0 .0 97)nmol/g及( 76.4± 9.2 )U/L ,差异有显著性 (P <0 .0 5)。结论　丹参可明显提高供体肝脏的保存效果 ,其作用机理可能主要与改善低温保存肝脏的能量代谢及抗氧自由基的作用有关     

肝血流阻断分步再灌注肝切除术的临床研究

目的　探讨一种在肝切除术中控制肝血流的新方法。　方法　通过改进肝切除时肝血流的阻断方法 ,对比分析观察组和对照组的切肝失血量、术后肝功能损伤等指标。　结果　观察组门静脉阻断时间为 ( 4 1± 12 )min ,切肝失血量为 ( 117± 79)ml,术后血清转氨酶为 ( 192± 12 6 ) μ L ,血清胆红素为 ( 195± 71) μmol L ,血清丙二醛 (MDA)为 ( 1.90 2± 0 .78) μmol L ;对照组全肝门阻断时间 ( 2 3± 9)min ,切肝失血量 ( 30 3± 2 72 )ml,术后血清转氨酶、胆红素和MDA分别为( 336± 193) μ L、( 10 0± 74) μmol L和 ( 2 .774± 0 .732 ) μmol L ,两组间比较有显著性差异。　 结论　分步再灌注肝血流阻断法能较长时间地控制肝血流 ,明显减少肝切除过程中的失血量 ,且对肝功能损伤较轻。     

缺血预处理和阿霉素预处理对大鼠肝脏低温保存损伤的保护作用

目的研究预处理对大鼠肝脏低温保存损伤的保护作用。方法应用大鼠肝脏离体非循环灌注模型 (IPRL) ,对供肝分别作缺血预处理 (IPC)和阿霉素预处理 (DPC) ,比较各组供肝低温保存损伤的程度。结果流出液中AST和ALT的酶学水平 ,IPC组 (40 1± 6 3、17 1± 0 5 )U L和DPC组 (43 6± 3 7、19 4± 0 8)U L显著低于未预处理 (NPC)组 (6 4 5± 8 2、2 3 8± 3 9)U L(P <0 0 5 ) ;胆汁分泌量及肝组织ATP含量 ,IPC组 (5 3 5± 10 2 ) μl、(6 2± 0 6 ) μmol g和DPC组 (5 0 5± 8 1) μl、(6 0±0 6 ) μmol g显著高于NPC组 (2 2 8± 9 7) μl、(2 6± 0 3) μmol g(P <0 0 5 ) ;肝组织丙二醛 (MDA)的含量 ,IPC组 (4 36± 0 2 6 )nmol g和DPC组 (4 5 1± 0 13)nmol g显著低于NPC组 (6 75± 0 17)nmol g(P<0 0 5 ) ;光镜及电镜结果显示 ,IPC组和DPC组肝细胞损伤的程度显著轻于NPC组 ;而IPC组与DPC组相比较 ,上述指标均无显著性差异 (P >0 0 5 )。结论预处理对供肝低温保存损伤具有明显的保护作用 ,药物预处理可以模拟IPC的效果。药物预处理为临床提供一种安全有效的预处理方法。     

腹腔海水浸泡对失血犬的影响

目的　探讨腹腔海水浸泡对失血犬的影响。方法　将实验犬 2 1条随机均分为失血组 (A组 )、腹腔海水浸泡组 (B组 )、失血及腹腔海水浸泡组 (C组 )。观察各组犬腹腔海水浸泡前后心排血量 (CO)、平均动脉压 (MAP)和血浆渗透压、乳酸、丙二醛 (MDA)、及超氧化物歧化酶 (SOD)水平变化。结果　C组动物腹腔海水浸泡 3hCO、MAP、SOD水平分别由浸泡前 ( 4 .3 5± 0 .5 0 )L/min、( 2 0 .1± 1.3 )kPa、( 182 .1± 14 .5 )U /L显著降低至 ( 1.3 7± 0 .11)L/min、( 9.6± 2 .7)kPa、( 5 1.4± 11.8)U /L ,而MDA及乳酸水平则分别由浸泡前 ( 5 .9± 0 .2 ) μmol /L、( 2 .3± 0 .4)mmol/L显著升高至 ( 2 6.4± 3 .2 ) μmol/L、( 8.7± 1.4)mmol/L(与A、B组比较P <0 .0 5 )。 结论　腹腔海水浸泡可加重失血犬血流动力学紊乱及自由基损伤。     

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.