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.     

二种大鼠供肝原位肝移植术后近期死因的分析

目的　分析大鼠正常心跳供体 (HBD)和心跳停搏供体 (NHBD)原位肝移植术后近期死因的异同。方法　雄性SD大鼠随机分成HBD和NHBD两组 ;NHBD组又分别设心跳停搏 30min(NHBD 30 )和 45min(NHBD 45 )两组。每组各行原位肝移植 5 0、30和 30次。结果　HBD和NHBD组冷缺血、无肝期、IVC阻断、受体手术时间分别为 6 9 76± 1 5 2和 70 32± 1 5 3min、16 46± 0 96和 16 40± 0 73min、2 2 5 6± 1 73和 2 2 75± 1 16min、89 38± 3 75和 90 5 8± 3 76min ;HBD组术后近期 (1周 )共有 5只受体分别死于原发性移植肝无功能 (1)、麻醉过深 (1)、肺部感染 (2 )和SVC吻合口漏 (1) ;而NHBD组术后近期共有 36只受体分别死于原发性移植肝无功能 (17)、麻醉过深 (4)、无肝期较长 (3)和供肝再灌注后渗血 (12 )。结论　二种供体原位肝移植术后的近期死因确实存在着差异。     

大鼠心跳停搏供肝在原位肝移植术中损伤的预防

目的：探讨预防和减轻大鼠心跳停搏供肝在原位肝移植术中的损伤，以提高手术成功率。方法：雄性SD大鼠随机分为心跳停搏热缺血30min(N-30)和45min(N-45)两组;，每组分别行原位肝移植术30只次。同时，根据是否对供体手术方法进行改进又分为常规组和改良组。结果：(1)常规组和改良组的冷缺血时间分别为(70.04±1.48)和(70.36±1.42)min(P>0.05)，无肝期均为(16.40±0.73)min，肝下下腔静脉阻断时间均为(22.75±1.16)min，受体手术时间均为(90.58±3.76)min。(2)N-30和N-45常规组分别有5和9只受体术后死于原发性移植肝无功能，而改良组仅为1和2只(40%∶12%,P<0.05);(3)N-30和N-45组因术中分别出现供肝损伤致再灌注后供肝大量渗血、无肝期过长、切除受体肝脏时麻醉过深，而各有5和7，2和1，2和2只受体术后死亡。(4)N-30和N-45组术后1周存活率分别为50%和30%(P<0.05)。结论：预防心跳停搏供肝游离时损伤、供肝再灌注后渗血、无肝期过长和切除受体肝脏时麻醉过深是大鼠心跳停搏供肝原位肝移植手术成功的关键。     

人ⅠκBα突变体对大鼠肝移植缺血再灌注中炎性因子的影响

目的探讨人IκBα突变体(IκBαM)对大鼠肝移植缺血再灌注中炎性因子的影响。方法SD大鼠随机分4组：组Ⅰ为假手术组,组Ⅱ为对照组,组Ⅲ为PcDNA 3．0组,组Ⅳ为PcDNA 3．0-I⒘BαM组。应用免疫组织化学、逆转录-聚合酶链反应(RT-PCR)测定肝组织中肿瘤坏死因子-α(TNF-α)、细胞黏附分子-1(ICAM-1)的表达,酶联免疫吸附(ELISA)检测血清中TNF-α的表达,同时检测肝脏酶学的变化。结果Ⅱ、Ⅲ组与Ⅳ组比较：术后12 h TNF-α免疫组织化学阳性率分别为84%、80%、55%,ICAM-1免疫组织化学阳性率分别为74%、76%、47%,差异有统计学意义(P＜0．05)；术后2、12 h TNF-α和术后12 h ICAM-1mRNA的表达差异有统计学意义(P＜0．05)；术后2、12 h血清TNF-α表达差异有统计学意义,以2 h为显著(258．50±46．19 vs 147．45±36．04；244．83±18．08 vs 147．45±36．04,P＜0．05)；肝脏酶学指标(ALT)在各时点差异有统计学意义(P＜0．05)。结论IκBαM通过抑制炎性因子的表达减轻大鼠肝移植缺血再灌注损伤。     

左旋卡尼汀对离体心肌缺血再灌注损伤的保护作用

目的探讨左旋卡尼汀增补于停搏液中对离体鼠心再灌注损伤的保护作用。方法将32只SD大鼠随机分为左旋卡尼汀3个剂量(2．5、5．0、10．0 mmol／L)组和对照组。离体鼠心在改良的Langendorff灌注模型上30 min预灌注,120 min缺血、60 min再灌注。缺血前及再灌注期间测定血流动力学指标、心肌超氧化物歧化酶(SOD)、丙二醛(MDA)含量和三磷酸腺苷(ATP)水平。电镜观察心肌超微结构。结果再灌注60 min后,左旋卡尼汀5 mmol／L剂量组和10 mmol／L剂量组与对照组相比,冠脉流量(CF)[(68．39±12．71)％、(72．27±6．27)％比(44．94±13．26)％]、左室收缩压(LVSP)[(73．04±3．32)％、(77．8±3．80)％比(62．29±4．14)％]、左室舒张末压(LVEDP)[(0．38±0．01)、(0．36±0．01)比(0．43±0．01)mmHg(1mmHg=0．133 kPa)]、左室压力变化速率(+dp／dt)[(69．66±0．92)％、(71．34±0．66)％比(62．16±1．21))％]、(-dp／dt) [(68．39±12．71)％、(72．27±6．27)％比(44．94±13．26)％],其差异均有统计学意义(P＜0．01)。心肌超微结构的改善,也优于对照组,尤其是10 mmol／L剂量组,2．5 ml／L组没有变化。左旋卡尼汀5 mmol／L剂量组和10 mmol／L剂量组丙二醛(MDA)含量显著低于对照组(19．04±0．41)、(17．60±0．53)nmol／mg蛋白比(27．36±1．23)nmol／mg蛋白,P＜0．01),超氧化物歧化酶(SOD) [(218．20±14．91)、(238．63±7．61)U／mg蛋白比(141．80±15．17)U／mg蛋白]含量和三磷酸腺苷(ATP)水平[(3．83±0．20)、(5．26±0．18)μmol／L比(1．36±0．08)μmol／L]显著高于对照组(P＜0．01)。结论左旋卡尼汀(5～10 mmol／L)增补于停搏液中可减轻心肌缺血再灌注损伤,具有良好的心肌保护作用并在一定范围内呈剂量依赖性,10mmol／L剂量组心肌保护效果最佳。     

L-精氨酸对心肺移植缺血再灌注损伤的保护作用

目的探讨一氧化氮(NO)前体L-精氨酸(L-Arg)在心肺移植中对心肺缺血再灌注损伤的保护作用。方法将30条成年犬随机分为对照组、实验A(L-Arg 100 mg／kg体重)、B(L-Arg 500 mg／kg体重)3组,每组10条,采用标准法行心肺移植,A、B组心肺保护液中加入不同剂量L-Arg,供心肺放入4℃EC液保存4-5 h。监测心率、平均动脉压(MAP)、肺动脉平均压(MPAP),股静脉血一氧化氮(NO)、超氧化物歧化酶(SOD)、丙二醛(MDA)、心肌肌钙蛋白I(cTnI)、乳酸脱氢酶同工酶 (LDH)含量、股动脉血氧分压(PaO2),测定肺干湿重比(W／DR)及观察心肺超微结构以评价心肺保护的效果。结果主动脉开放60 min,B组NO(82．76±12．34)μmol／L、A、B组SOD(60．19±12．42)、 (100．38±16．55)NU／ml较对照组(29．43±12．42)μmol/L、(26．65±5．68)NU／ml高(P<0．05),B组 cTnI(11．07±2．62)mg／L、MDA(2．48±0．51)nmol／ml、LDH(592．8±51．92)U／L较对照组(23．16± 2．76)mg／L、(4．48±0．54)nmol／ml、(719．80±292．16)U／L低(P<0．05),B组PaO2(207．60± 32．72)mmHg(1 mm Hg=0．133 kPa)高于对照组(130．20±13．36)mm Hg(P<0．05),A、B组W／DR (84．82±1．14)％、83．84±1．63)％小于对照组(88．44±1．42)％(P<0．05),电镜检查A、B组心肺损伤轻于对照组。结论供心肺可安全保存4-5 h,在心肺移植实验中加入L-Arg可使NO含量增加, 减轻心肺缺血再灌注损伤,B组(500 mg／kg体重)效果更好。     

大鼠肝缺血再灌注时三七总皂甙的保护作用

在肝脏外科中，常需要采取肝血流阻断以控制术中的出血，但缺血再灌注会造成肝损伤。作者用大鼠按Asakawa的方法造成肝缺血再灌注模型．比较维拉帕米和三七总皂甙对大鼠肝缺血再灌注损伤的保护效果。用雄性重300～350gSD大鼠分成4组，单纯切肝组、对照组(注人生理盐水)、注入维拉帕米50mg/kg组，三七总皂甙1.25ms／kg组，在阻断肝血流前5min注入。观察大鼠肝血流阻断90min再灌注后的生存率、肝功能、肝脏的病理和丙二醛、超氧化物歧化酶(SOD)的改变。结果：三七总皂甙与维拉帕米比较在提高大鼠的生存率(120min分别为63.3％比36.0％，P<0．05)，降低ALT(2118±430比3401±592，P<0．01)，减轻肝细胞坏死(5％～25％比20％～40％)，以及提高SOD活性(149±12比125±16，P<0．05)方面均强于维拉帕米。实验表明，三七总皂甙是肝缺血再灌注损伤的有效保护药物。     

缺血后处理对猪心肌细胞Fas基因蛋白表达及Caspase-3活性的影响

目的探讨缺血后处理对猪心肌细胞Fas基因蛋白表达及Caspase-3活性的影响。方法24只小型约克猪(体重35～40kg)被随机分为4组。组1(ACC组,n=6)：于CPB开始后并行循环45 min,阻断主动脉90 min,开放主动脉后心脏再灌注120 min；组2(pre-con组,n=6)：升主动脉阻断前进行心脏缺血预处理(阻断升主动脉5 min、开放10 min,重复3次),余处理与组1相同；组3(post-con组,n=6)：并行循环45 min,阻断主动脉90 min,开放主动脉后心脏再灌注120 min；再灌注开始进行缺血后处理(阻断升主动脉30 s后开放30 s,重复3次,共3 min)；组4(pre-con +post-con组,n=6)：升主动脉阻断前进行心脏缺血预处理(阻断升主动脉5 min、开放10 min,重复3次),阻断主动脉90 min,开放主动脉心脏再灌注120 min,再灌注开始进行心肌缺血后处理(阻断升主动脉30 s、开放30 s,重复3次共3 min)。在再灌注结束后取左心室全层心肌适量并固定。用原位化学法(TUNEL)观察各组心肌细胞凋亡,流式细胞法检测Fas基因蛋白表达及Caspase-3的活性。在CPB前、缺血90 min、再灌注30、60、120 min采静脉血检测血MDA、SOD水平。结果原位化学法测得心肌细胞凋亡率组2(10．46±0．91)%、组3(9．68±0．59)%和组4(11．35±1．37)%显著低于组1(19．75±1．81)%(P＜0．05)；流式细胞法测得Fas,Caspase-3荧光表达指数(FI),组2(1．24±0．13和1．32±0．13)、组3(1．27±0．07和1．33±0．08)和组4(1．27±0．14和1．31±0．12)显著低于组1(1．74±0．11和1．99±0．12)(P＜0．05)；与组1相比,MDA血浆浓度组2、组3和组4显著低于组1,而SOD浓度却显著高于组1(P＜0．05)。组2、组3和组4上述指标差异无统计学意义(P＞0．05)。结论Fas、Caspase-3表达改变参与了心肌细胞凋亡及缺血再灌注损伤过程；缺血后处理可以明显减少心肌细胞凋亡,抑制缺血再灌注损伤。心肌细胞凋亡的减少与Fas基因蛋白的下调、抑制Caspase-3活性及氧化应激有关；缺血后处理与缺血预处理相比可以同等程度的减少心肌细胞凋亡。本实验未观察到缺血预处理和缺血后处理的叠加作用。     

亚低温对肝缺血再灌注损伤的保护作用

目的　探讨亚低温对肝缺血再灌注损伤的保护作用机制。方法　将 18只犬随机分为 3组 :非缺血对照组 (n =6 )、缺血再灌注组 (n =6 )和亚低温处理组 (肝周充填碎冰块造成肝脏亚低温 ,n =6 )。对各组肝上下腔静脉血进行谷丙转氨酶 (ALT)、谷草转氨酶(AST)、乳酸脱氢酶 (LHD )以及丙二醛 (MDA)和超氧化物歧化酶 (SOD)、过氧化氢酶 (CAT)、谷胱甘肽过氧化酶 (GSH PX)活性及总抗氧化 (TAX )能力测定。结果　全肝缺血再灌注后ALT ,AST ,LDH和MDA含量明显上升 (P <0 .0 1) ,SOD ,CAT ,GSH PX活性及TAX能力明显下降 (P <0 .0 1) ;而亚低温处理组与缺血再灌注组比较 ,ALT ,AST ,LDH和MDA含量明显下降 (P <0 .0 1) ,SOD ,CAT ,GSH PX活性及TAX能力明显上升 (P <0 .0 1,P <0 .0 5 )。结论　亚低温能增强肝组织自身抗氧化能力 ,减轻肝缺血再灌注后氧自由基对肝脏的损伤。     

肝移植大鼠肝窦内皮细胞的损伤及PGE1对其的保护作用

目的　探讨肝移植大鼠术后早期肝窦内皮细胞功能的改变及前列腺素E1(PGE1)对其的保护作用。方法　用“两袖套法”建立大鼠原位肝移植模型 ,其中A组为正常大鼠空白对照组 ,B组为正常大鼠供体肝移植手术对照组 ,C组为休克性大鼠供体肝移植实验对照组 ,D组为PGE1保护的休克性大鼠供体肝移植实验组 ,每组各 8只。肝移植各组 (无特别说明均指受体 )于术后 6h取血 ,检测其血清中的肝脏酶学 (ALT、LDH )、丙二醛 (MDA)和一氧化氮 (NO) ,以及血浆内皮素 (ET)水平 ,并取肝组织作常规病理学检查 ,比较各组有无差异。结果　各移植组供肝冷保存时间及无肝期均接近 ,分别为 (2± 0 .5 )h和 (15± 3 )min ;B、D组术后 6h全部存活 ,存活率 10 0 % ;C组术后 6h存活 5只 ,存活率 62 .5 %。与C组比较 ,D组ALT、LDH、MDA、ET明显降低 (P<0 .0 5 ) ,NO明显升高 (P<0 .0 5 )。C组肝脏病理学检查发现有明显的组织学损害 ,而B、D组肝脏组织结构基本完好。结论　肝移植可造成肝窦内皮细胞明显损害 ,血清NO和血浆ET水平可较好地反映肝窦内皮细胞的功能状态。PGE1通过稳定血流动力学和稳定肝窦内皮细胞质膜 ,可减轻移植肝肝窦内皮细胞的损害。     

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.