三种消化酶在大鼠胰岛分离纯化中的效果比较

目的　分别用 3种酶消化大鼠胰腺 ,比较分离纯化后胰岛细胞的收获量、纯度、活性和功能。方法　将 2 1只SD大鼠按应用释放酶、胶原酶P、胶原酶V消化胰腺随机均分为A、B、C组。结果　A组的胰岛细胞收获量比B组或C组多 ( 93 0± 78比 692± 68或 70 6± 70 ,P <0 .0 5 ) ;纯度比B组或C组高 ( 93 .8± 2 .3比 88.4± 2 .0或 89.2± 2 .1,P <0 .0 5 ) ;成活率比B组或C组高( 97.2± 1.4比 92 .2± 1.9或 92 .9± 2 .1,P <0 .0 5 ) ;A组培养后胰岛素分泌量和葡萄糖刺激时胰岛素分泌量比B组或C组多 (P <0 .0 5 ) ;A组逆转糖尿病大鼠的高血糖状态时间比B组或C组长( 7.5± 1.3比 5 .8± 1.6或 6.3± 1.2 ,P <0 .0 5 )。结论　与胶原酶P和胶原酶V比较 ,释放酶消化大鼠胰腺可提高胰岛细胞的收获量、纯度、活性和功能。     

血管紧张素Ⅱ对大鼠增生前列腺细胞增殖和凋亡的影响

目的了解血管紧张素Ⅱ对良性前列腺增生(BPH)大鼠前列腺细胞增殖和凋亡的作用。方法成年雄性Wistar大鼠随机分为正常组(A组),BPH模型组(B组)和BPH+血管紧张素转化酶抑制剂依那普利组(C组),每组10只。B组在双侧睾丸切除后1周开始皮下注射丙酸睾酮并灌饲生理盐水,C组在双侧睾丸切除术后1周开始皮下注射丙酸睾酮并灌饲依那普利。4周后观察各组大鼠前列腺重量和组织学变化,Ki-67免疫组化染色及TUNEL染色测定前列腺上皮和间质细胞的增殖和凋亡指数。结果3组大鼠前列腺指数[前列腺湿重(mg)／体重(g)]分别为1．54±0．09,1．65±0．07和1．59±0．09,B组大鼠前列腺指数显著大于A组和C组(P<0．05)。光镜显示B组前列腺上皮细胞增生明显,C组上皮细胞明显萎缩。A组上皮和间质细胞增殖率分别为(1．4±0．4)％和(1．1±0．4)％,B组为(3．0±0．4)％和(1．4±0．4)％,C组为(2．1±0．5)％和(1．2±0．5)％,B组上皮细胞增殖率显著高于A组和C组(P<0．05),而3组间质细胞的增殖率比较差异无统计学意义(P>0．05);3组上皮细胞凋亡率分别为(1．2±0．5)％,(1．1±0．3)％和(1．1±0．5)％(P>0．05)。结论血管紧张素Ⅱ在大鼠BPH组织中表达上调。血管紧张素Ⅱ可能影响大鼠前列腺细胞的增殖,但对细胞凋亡影响不明显。     

一步法联合冻存提高大鼠胰岛冻存质量的研究

目的探讨提高大鼠胰岛冻存质量的方法,以期为建立胰岛库奠定基础。方法将受体鼠分为实验组A组:即一步法联合冻存的胰岛移植组;对照组B组:新鲜的胰岛移植组;对照组C组:逐步法冻存的胰岛移植组。观察3组之间胰岛收获率,活性及移植后效果等方面的差异。结果纯化后收获大鼠胰岛每只(826.87±93.24)IEQ。A组平均胰岛收获率为(87±4)%,高于C组的胰岛收获率(81±4)%。A组和C组经过胰岛刺激素释放实验后均有较B组高的基础胰岛素释放量,但刺激指数则明显低于B组的637.3±39.5。胰岛移植入糖尿病鼠受体后,A组和B组在移植后1周即恢复血糖为正常值,并维持到观察结束。而C组中则需要较长时间纠正血糖到正常。移植(2011.14±114.22)IEQ胰岛在A组和B组可达到100%纠正糖尿病。结论采用全新的细胞内低温保存液(HTS)结合细胞冻存液(DMSO)对大鼠胰岛进行一步法冻存取得了明显优于用DMSO逐步冻存的效果。     

三维微重力培养大鼠胰岛细胞的实验研究

目的　应用三维微重力组织培养对大鼠胰岛细胞的存活率及分泌功能进行研究。方法将大鼠胰岛细胞分离消化后分别进行二维普通培养 (Ⅰ组 )及三维微重力条件培养 (Ⅱ组 ) ,应用双硫腙 (DTZ)染色法 ,对胰岛细胞进行特异性染色鉴定 ;采用AO PI双染色法对两组培养 3d、7d、14d的胰岛细胞存活率进行检测 ;应用放射免疫法检测两种不同培养方法培养液中胰岛素分泌水平。结果　DTZ染色后胰岛呈桔红色 ,清晰可见。培养 7d和 14d时 ,Ⅱ组胰岛细胞存活率分别为(0 90 0 0± 0 0 10 7) %和 (0 80 38± 0 0 0 92 ) % ,均明显高于Ⅰ组 (P <0 0 1)。胰岛素测定结果表明 ,培养 7d时 ,Ⅱ组胰岛素水平为 (70 875± 0 31)mU/L ,Ⅰ组胰岛素水平为 (41 2 4 6± 0 35 )mU/L ,二者差异有显著意义 (P <0 0 1)。在培养的 14d、2 1d和 30d时 ,Ⅱ组胰岛素的分泌水平也均高于Ⅰ组(P <0 0 1)。结论　三维微重力培养组的胰岛细胞存活率及胰岛素分泌功能都优于二维普通培养组。     

胰岛素对体外培养兔骨骼肌肌管蛋白降解的调节作用

目的观察胰岛素对体外培养兔骨骼肌肌管蛋白降解的调节作用。方法无菌分离幼兔下肢骨骼肌肌肉,采用组织块法分离、培养成肌细胞,待其融合形成肌管,采用L-[3,5-3H]-酪氨酸标记肌管内蛋白后,随机分为对照组(用含体积分数10％胎牛血清的DMEM培养液培养)、胰岛素组(用含100 nmol／L胰岛素+体积分数10％胎牛血清的DMEM培养液培养)、地塞米松组(用含100 nmol／L地塞米松+体积分数10％胎牛血清的DMEM培养液培养)和胰岛素+地塞米松组(用含100 nmoL／L胰岛素+100 nmol／L地塞米松+体积分数10％胎牛血清的DMEM培养液培养),每组含24孔肌管。培养24 h后．应用液体闪烁计数仪测定培养液和肌管内L-[3,5-3H]-酪氨酸的含量,计算肌管内蛋白的降解率。RNA印迹法测定肌管内泛素-蛋白酶体C2亚基mRNA的表达水平,以其与内参照甘油醛-3-磷酸脱氢酶的灰度值之比表示。结果肌管内蛋白的降解比:地塞米松组为0．50±0．03,明显高于对照组(0．38±0．04,P<0．01);胰岛素组为0．35±0．03,明显低于对照组(P< 0．05);胰岛素+地塞米松组为0．41±0．03,明显低于地塞米松组(P<0．01),但仍高于对照组(P< 0．05)。肌管内泛素-蛋白酶体C2亚基的mRNA表达水平:与对照组(泛素2．4 kb条带为0．82±0．15、1．2 kb条带为0．60±0．10,C2亚基为0．75±0．16)比较,地塞米松组(泛素2．4 kb条带为2．15±0．23、1．2 kb条带为1．50±0．14,C2亚基为1．50±0．13)明显升高(P<0．01);胰岛素+地塞米松组(泛素2．4 kb条带为1．25±0．17、1．2 kb条带为0．85±0．09,C2亚基为0．90±0．15)明显低于地塞米松组(P<0．01);胰岛素组(泛素2．4 kb条带为0．85±0．07、1．2 kb条带为0．65±0．12,C2亚基为0．76±0．09)与对照组相近(P>0．05)。结论胰岛素对兔骨骼肌肌管内泛素-蛋白酶体途径的活性和蛋白代谢分别有较弱的促进与抑制作用,但能有效拮抗地塞米松诱导的该途径活性的增强和蛋白的高降解,其机制尚有待进一步探讨。     

提高冻存胚胎胰岛移植效果的实验研究

目的探讨三维组织细胞旋转培养系统(RCCS)对胚胎胰岛冻存复苏后质量的影响。方法将胚胎胰岛平均分为3组,实验组1、2为胚胎胰岛冻存前后分别用RCCS培养和普通培养,对照组新鲜胰岛经RCCS培养。切取胚胎胰腺,胶原酶V消化,纯化。然后进行标准冻存步骤,复苏后继续培养。并检测各组胰岛数量、活性、胰岛素刺激实验结果。结果纯化后收获胰岛最多每个胚胎5012.73IEQ,最少2432.68IEQ,平均(3548.07±273.46)IEQ。微重力培养组胰岛细胞存活率、胰岛素释放量、胰岛素刺激指数等均高于普通培养组。移植经过微重力培养的(2000±1)%IEQ新鲜胚胎胰岛或冻存胚胎胰岛在移植后1周内可达100%纠正糖尿病。结论微重力旋转培养有利于胰岛细胞的生长繁殖,使胰岛具有更好的胰岛素分泌能力,该方法同胰岛冻存相结合,可以进一步提高胰岛的冻存效果,为胰岛库的成功建立探索出一条新的途径。     

抑制巨噬细胞对异种胰岛移植物的作用

目的　观察普伐他汀 (pravastatin)对异种胰岛移植物存活的影响。方法　将猪→小鼠胰岛移植模型分成A组 (对照组 )、B组 (CsA组 )、C组 (普伐他汀组 )、D组 (CsA +普伐他汀组 )。观察指标 :移植物存活时间、病理检查、免疫组化染色、血清NO含量及移植物IFN γmRNA的表达。结果　A、B、C和D组移植物平均存活时间分别为 (6 .2±0 .82 )d、(9.2± 1 .92 )d、(7.2± 1 .30 )d及 (1 1 .2± 1 .76)d,D组存活时间明显长于其它 3组 (P<0 .0 5) ;D组移植物浸润细胞较其它 3组少。术后第 4天 ,血清NO水平A组为 (1 0 5 .8± 1 9.3)mmol/L ,明显高于B组的 (88.2± 2 1 .4)mmol/L(P<0 .0 5)、C组的 (70 .7± 1 7.8)mmol/L(P<0 .0 1 )及D组的 (56 .3± 1 6 .4)mmol/L(P<0 .0 1 ) ,出现移植排斥时 ,C、D组的血清NO水平分别为 (83 .7± 1 0 .6)mmol/L及 (71 .3± 1 3 .8)mmol/L ,仍较A组低 (P<0 .0 5) ,B组为 (1 0 4 .7± 1 6 .3)mmol/L ,与A组比较差异无显著性意义 (P>0 .0 5)。术后第 4天血清IFN γmRNA表达 ,D组为 2 3 .5± 4 .6 ,较A组的2 8.8± 4 .8低 (P<0 .0 5) ,而B、C组与A组间差异无显著性意义 (P>0 .0 5)。结论　普伐他汀能抑制巨噬细胞活性 ,延长异种胰岛移植物存活 ,尤其与CsA联用效果更好     

微重力培养的新鲜和冻存胰岛联合移植治疗1型糖尿病

目的经微重力培养的新鲜和冻存胰岛联合移植提高1型糖尿病的治疗效果。方法将分离纯化的大鼠胰岛分为（1）体外实验组：实验组1．1：冻存的胰岛经微重力培养；实验组2．1：冻存的胰岛在普通培养基中培养；对照组1：新鲜大鼠胰岛经微重力培养。观察胰岛收获率和体外胰岛素分泌情况。（2）胰岛移植组：即将新鲜和冻存的胰岛经微重力或普通培养7d后分别移植入受体鼠体内，观察移植效果。结果经微重力培养的各组胰岛收获率、DNA含量和胰岛素含量高于普通组。普通培养组在培养后期胰岛素分泌明显下降，并且胰岛素刺激指数明显低于经微重力培养组（P〈0．05）。移植经过微重力培养的500 IEQ新鲜胰岛和1500 IEQ冻存胰岛在移植后1周内可达100％纠正糖尿病，全部受体维持正常血糖耐受曲线一直到观察结束。结论采用细胞内低温保存液（HTS）结合细胞冻存液（DMSO）对大鼠胰岛进行冻存前后经微重力培养可以明显提高胰岛冻存质量，是目前胰岛冻存的最佳选择。使经微重力培养的新鲜和冻存胰岛联合移植一次治愈糖尿病成为可能，并有效的节约了胰岛资源，提高了移植效果。     

低温微重力培养对大鼠胰岛细胞质量影响的实验

目的:研究低温微重力对大鼠胰岛移植质量的影响，以期减少体外培养对胰岛活性和数量的影响，提高胰岛移植质量。方法:将分离纯化的大鼠胰岛分为3组：大鼠新鲜胰岛移植组（于移植前在普通培养基中培养21 d,对照组）；实验1组（大鼠新鲜胰岛在37 ℃ RCCS中培养21 d）；实验2组（新鲜大鼠胰岛在26 ℃ RCCS中培养14 d后复温至37 ℃继续在37 ℃ RCCS中培养7 d）。　观察各种培养液中的胰岛素含量。并将上述3个实验组不同条件培养的胰岛分别以2000IEQ胰岛移植量植入糖尿病大鼠体内，并观察10周。结果:实验2组的胰岛存活率、胰岛素分泌水平及胰岛素刺激指数均高于对照组和实验1组，差异有统计学意义(P＜0.05)。21 d时实验2组胰岛存活率高达(67.4±4.6)%，而对照组和实验1组胰岛存活率分别降至(28.1±3.3)%和(50.3±3.5)%，3组间差异有统计学意义(P＜0.05)。给糖尿病大鼠移植实验1，2组的胰岛后均能控制血糖至正常水平，但实验2组胰岛移植对糖尿病大鼠7 d内血糖控制优于实验1组；对照组血糖控制差，3组间两两比较均有统计学差异（均P＞0.05）。结论:大鼠胰岛经低温微重力培养后移植，可以明显提高1型糖尿病大鼠的治疗效果。     

小体积肝移植和辅助性原位小体积肝移植治疗猪急性肝功能衰竭的近期疗效观察

目的观察小体积肝移植和辅助性原位小体积肝移植治疗猪急性肝功能衰竭的近期疗效。方法急性肝功能衰竭猪随机分为3组接受肝移植治疗:A组行全肝移植(n=5);B组行小体积肝移植(n=5);C组行辅助性原位小体积肝移植(n=5)。各组动物开腹后即刻、切脾后即刻和再灌注后30 min分别监测门静脉压力,并观察术后生化指标变化、病理改变和1周生存率。结果A、B和C三组的移植肝重量与受体体重之比分别为(2．44±0．30)％、(0．76±0．02)％和(0．75±0．03)％。再灌注后30 min,B组移植肝门静脉压力显著高于其它两组(A:B:C=13．3:17．5:12．2 cmH2O, P<0．01),C组原肝门静脉压力显著高于移植肝门静脉压力(14．3:12．2 cmH2O,P<0．05)。A组和C组术后第2天起血清天冬氨酸转氨酶、总胆红素、凝血酶原时间、乳酸和血氨水平明显下降,术后第7天基本恢复至正常水平。B组术后上述生化指标一直维持在较高的水平,术后第2～4天明显高于其它两组(P<0．01)。A组、B组和C组1周生存率分别为100％、20％和80％,B组明显低于其它两组(P<0．05)。结论辅助性原位小体积肝移植治疗急性肝功能衰竭近期疗效优于小体积肝移植,术中不必干预原肝门静脉。     

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.