聚对二氧环己酮血管外支架抑制移植静脉内膜增生的机制

目的 构建可降解性聚对二氧环己酮(PDS)血管外支架抑制移植静脉内膜增生的动物模型,探讨PDS外支架抑制移植静脉内膜增生的作用及其机制。方法 建立兔颈外静脉移植模型,24只新西兰大白兔分为单纯移植组(n=12)和PDS外支架组(n=12)。术后4周及12周取出移植静脉,测量移植静脉内膜、中层面积及厚度,免疫组织化学法和实时荧光定量逆转录-聚合酶链反应(RT-PCR)法检测增殖细胞核抗原(PCNA)、转化生长因子-β1(TGF-β1)和肾素-血管紧张素Ⅱ受体1( AT1 R)表达。结果 24只兔均存活,移植血管全部通畅。外支架组中膜面积、内膜面积、中膜厚度、内膜厚度各值皆小于单纯移植组,差异有统计学意义(P＜0.05)。免疫组织化学与RT-PCR检测表明血管外支架组TGF-β1在外膜中过度表达,而中膜和内膜表达减少。术后4周,外支架组AT1R表达水平低于对照组,12周时,两组AT1R表达水平都降低,差异无统计学意义(P＞0.05)。结论 大孔隙、非限制性PDS血管外支架通过形成新生外膜、调节细胞因子再分布等机制有效地抑制内膜和中膜的增生,其用于抑制移植静脉内膜增生是可行的。     

非限制性外支架防治移植静脉狭窄的早期形态学观察

目的 探讨非限制性外支架防治移植静脉内膜增生的效果及其可能的作用机制。方法新西兰白兔36只随机分成两组，每只均实施颈外静脉-颈总动脉移植术，支架组（S组）在移植静脉外套以直径6mm的非限制性涤纶外支架，对照组（NS组）移植静脉外无外支架，分别于术后7、14、28d取材进行观察。术后应用彩色多普勒超声观察移植静脉的通畅情况。组织切片进行HE和弹力VG染色和抗α-平滑肌肌动蛋白（α-SMA）免疫组织化学染色。采用计算机图像分析系统测量移植静脉内膜、中膜的厚度和面积，管腔面积，并计算内膜增值率（即内膜面积，内弹力板包围面积）。结果（1）S组术后死亡1只，闭塞性血栓形成1只，在支架与移植静脉之间有“果冻样”物质（新外膜）形成；NS组术后偏瘫并死亡1只，血栓形成1只。超声检查移植静脉通畅情况与取材时结果完全一致。（2）染色显示：术后7-28d，S组和NS组移植静脉内膜和中膜逐渐增生，S组新外膜为肉芽肿样增生，内有较多炎症细胞浸润。（3）计算机图像分析结果：S组和NS组内膜、中膜的厚度和面积均逐渐增加，术后7d时，S组的内膜厚度、面积和内膜增生率与NS组的差别无统计学意义，P〉0．05；术后14、28d，S组的内膜厚度、面积和内膜增生率均小于NS组，P〈0．05；术后1-4周，S组的中膜的厚度、面积均小于NS组，P〈0．05。结论非限制性外支架可以抑制移植静脉内膜和中膜增生；在非限制性外支架和移植静脉之间可以生成新外膜，新外膜的生成在防治内膜增生的过程中可能发挥了重要作用。     

血管外支架预防猪大隐静脉移植血管再狭窄的实验研究

目的以猪大隐静脉-颈总动脉旁路移植动物模型为基础,观察涤纶血管外支架支持预防静脉移植血管内、中膜增生的作用。方法将10只25~30kg普通长白猪行双侧大隐静脉-颈总动脉旁路移植术(端侧吻合),一侧静脉移植血管放置涤纶外支架(实验组),另一侧作为对照(对照组)。术后35d取出移植血管进行组织学和免疫组织化学检测。结果对照组静脉移植血管内膜增生较实验组明显增加(0.4872±0.0706mm vs.0.2259±0.0553mm,P<0.01);对照组中膜增生亦较实验组增加(0.6246±0.0859mm vs.0.4201±0.0615mm,P<0.01);对照组内膜面积是实验组的2倍,中膜面积是实验组的近1.5倍。实验组内膜及中膜内侧区域增殖细胞核抗原(PCNA)、血小板源性生长因子(PDGF)阳性细胞显著减少,PCNA从7.98%±4.06%减少至3.35%±0.95%(P<0.01),PDGF从9.47%±5.35%减少至2.67%±0.97%(P<0.01)。结论非限制性涤纶血管外支架可以显著抑制大隐静脉移植血管新内膜及中膜增生,可能预防大隐静脉移植血管的再狭窄。     

重组arresten蛋白对自体移植静脉内膜增生的抑制作用

目的 观察原核表达人arresten重组蛋白对自体移植静脉内膜增生的抑制作用.方法 用pRSET原核表达系统表达并纯化人arresten重组蛋白.将Wistar大鼠颈外静脉移植于腹主动脉,建立大鼠自体静脉移植模型,实验分3组:假手术组、移植对照组和移植实验组.自术后第3天起,皮下注射给予arresten重组蛋白(每日4 mg/kg体重)处理.4周后取移植静脉组织标本,进行病理组织学观察与免疫组织化学染色分析.结果 移植组移植静脉均呈现典型的内膜增生、肥厚,导致血管管腔狭窄;新生内膜主要有过度增殖的α-SMA染色阳性平滑肌细胞组成.移植实验组移植静脉内膜增生受到明显抑制,新生内膜面积(0.12±0.07)mm2及新生内膜/中膜面积比(0.373±0.085)均显著低于对照组[(0.38±0.11)mm2,1.621±0.086,P<0.01];并且实验组移植静脉新生内膜细胞PCNA标记指数显著低于对照组[(15.62±3.97)%比(56.36±3.49)%,P<0.01].结论 重组arresten蛋白通过抑制新生内膜平滑肌细胞的增殖能有效抑制自体移植静脉内膜增生的发生发展,在防治血管重建术后再狭窄方面显示出良好的应用前景.     

静电纺丝血管外支架抑制静脉移植物内膜增生

目的 探讨聚-3-羟基丁酸与聚-4-羟基丁酸聚酯[P(3HB-co-4HB)]静电纺丝血管外支架预防静脉移植物内膜增生的机制.方法 静电纺丝技术制备P(3HB-co-4HB)血管外支架.SD大鼠随机分成2组,每组24只,建立颈外静脉-颈总动脉血管移植模型:无支架(Ns)组和非限制支架(PS)组.分别于术后3、7、14、28 d取静脉移植物标本,计算机图像系统分析内膜、中膜厚度和面积,免疫组织化学检测静脉移植物增殖细胞核抗原(PCNA)表达.逆转录-聚合酶链反应(RT.PCR)检测静脉移植物血小板源性生长因子.BB(PDGF-BB)和组织因子(TF)mRNA表达.结果 术后7、14、28 d支架组静脉移植物内膜与中膜的厚度和面积明显低于无支架组(P<0.05).两组PCNA表达均增加并在术后14 d最高,而支架组在术后7、14 d PCNA表达低于无支架组(P<0.05).术后3、7d支架组PDGF.BB和TFmRNA表达明显低于无支架组(P<0.01).结论 静电纺丝P(3HB-co-4HB)血管外非限制性支架能抑制静脉移植物内膜增生,并通过降低静脉移植物管壁早期组织因子表达发挥作用.     

PTFE血管加自体静脉段减轻动脉内膜增生的实验研究

目的:探讨PTFE人造血管加自体静脉段吻合对动脉内膜增生的缓和作用。方法:12只健康杂种犬的24条犬腿随机分成对照组及实验组。对照组股动脉阻断后,以PTFE人造血管直接行旁路转流术,实验组以自体颈外静脉段间置于PTFE与远端股动脉之间,术后第八周动脉造影后,收集标本行病理组织学观察及计算机图象分析测算增生内膜、中膜的厚度,增生内膜的截面面积、血管腔截面面积及两者的比值和静脉“动脉化”后中膜的厚度,同时,行间置静脉扫描电镜观察。结果:血管造影示两组通畅率分别为16.7％和66.7％(P<0.05);内膜厚度分别是483.5μm±67.3μm和147.1μm±38.6μm(P<0.1);中膜厚度组间差异不明显;增生内膜面积分别是5217±1123(pixel)和3117±890(pixel),分别占血管腔截面的80.9％±17.2％和47.7±13.7％(P<0.01);间置静脉呈动脉化表现。结论:间置自体静脉段能明显减轻PTFE管旁路手术后的动脉内膜增生,有效地提高血管手术后的通畅率。     

自体股静脉复合聚乙丙交酯血管外支架修复股动脉缺损的实验研究

目的 报道聚乙丙交酯(PGLA)血管外支架复合自体股静脉移植修复股动脉缺损的实验效果及其作用机制。方法 30只犬两侧股动脉各切除5cm，一侧用6cm自体股静脉修复，为对照组(B组)；另一侧在移植静脉上套1个PGLA血管外支架，为实验组(A组)。术后分别检测两组移植静脉的血流动力学、血管壁组织形态和细胞行为的变化。结果 两组内膜在术后1周即出现增殖，此后内膜厚度随时间递增直至第8周。PCNA阳性细胞百分数术后2周达到最大值，此后逐渐减少。但无论内膜增殖还是细胞增生A组都远小于同时间段B组，差异有非常显著性。结论 复合应用PGLA血管外支架通过有效控制移植静脉的扩张程度减轻移植静脉内膜的过度增生和管腔的狭窄，提高静脉移植修复动脉缺损的效果。     

自体股静脉复合血管外支架修复股动脉缺损的组织学变化

目的探讨复合聚乙丙交酯(PGLA)血管外支架对自体静脉修复动脉缺损的组织学变化的影响。方法以30只犬两侧股动脉各切除5cm,用6cm同侧股静脉移植修复,随机一侧复合PGLA血管外支架为A组;另一侧仅行自体股静脉移植为B组。术后1、2、4、6、8周取材,HE、Masson和弹力染色,光镜观察组织形态变化,进行图像分析,PCNA免疫组化染色观察平滑肌细胞增殖。结果两组移植静脉内膜厚度和截面积都较正常静脉差异有极显著意义(P<0.01),且随时间的推移而递增;两组间内膜厚度、截面积差异有极显著意义(P<0.01)。两组中膜厚度和截面积较正常静脉差异有显著意义(P<0.05),两组管腔截面积与正常静脉相比差异有极显著意义(P<0.01);两组间比较自第4周起差异有极显著意义(P<0.01)。移植静脉PCNA阳性细胞较正常静脉明显增加,术后2周达到高峰,而后逐渐减少,B组PCNA阳性细胞数高于A组,其中在术后前6周两者差异有极显著意义(P<0.01)。实验中A组移植的静脉无明显炎症反应,PGLA血管外支架保持较完整的结构,强度没有明显改变。结论复合应用PGLA血管外支架移植静脉内膜增生和平滑肌增殖减少,管腔狭窄较少。     

纤维蛋白胶联合转染金属蛋白酶组织抑制剂-1预防自体移植静脉再狭窄

目的 为减少冠状动脉旁路移植术后移植静脉再狭窄,探讨术中应用纤维蛋白胶联合转染金属蛋白酶组织抑制剂-1(TIMP-1)对自体移植静脉再狭窄的影响及其作用机制.方法 将24只新西兰大耳白兔随机分为3组,每组8只,即非支架组(NS组)、纤维蛋白胶外支架组(FS组)、纤维蛋白胶联合转染TIMP-1组(TS/FS组) 建立兔颈外静脉颈总动脉旁路移植术模型.术后28 d取出移植静脉桥,进行组织病理分析移植静脉内膜厚度、中膜厚度及内膜面积、中膜面积,用逆转录-聚合酶链反应(RT-PCR)和Western blot法检测各组移植静脉中TIMP-1基因的表达.结果 术后28d,TS/FS组移植静脉内膜厚度及内膜面积分别为(37.98 ±4.19) μm及(0.557±0.049) mm2,与NS组的( 76.87±4.32) μm、(1.025 ±0.103)mm2及FS组的(50.28 ±4.69) μm、(0.743±0.052) mm2比较,明显减少(P＜0.05);TS/FS组移植静脉中膜厚度及中膜面积分别为(28.45 ±3.01) μm及(0.458 ±0.053) mm2,与NS组的(55.98±4.33) μm、(0.944±0.084) mm2及FS组的(36.46±4.36) μm、(0.643 ±0.056)mm2比较,差异有统计学意义(P＜0.05).与NS组和FS组比较,TS/FS组TIMP-1基因的mRNA和蛋白表达明显增强,差异有统计学意义(P＜0.05).结论 纤维蛋白胶联合血管外膜TIMP-1转染能够实现移植静脉TIMP-1基因的过表达;纤维蛋白胶外支架联合TIMP-1对移植静脉内膜和中膜增生有协同抑制作用.     

壳聚糖纳米粒子携带反义增殖细胞核抗原寡核苷酸抑制血管移植后内膜增殖的实验研究

目的探讨壳聚糖纳米粒子携带反义基因在血管外科领域中的应用。方法雄性SPF级SD大白鼠54只,体重450～600g,随机分为实验组和对照组(n=27)。实验组取右侧颈静脉、颈动脉吻合口段灌注携带增殖细胞核抗原(proliferation cell nuclear antigen,PCNA)的反义寡核苷酸(antisens oligo deoxy nucleotides,ASODN)粒子后,移植至同侧颈动脉;对照组用同样方法灌注生理盐水。取造模后血管通畅的48只大白鼠(n=24)分别于第1、2、3、4周超声多普勒监测血流动力学,取标本行免疫组织化学染色、Western blot蛋白印迹检测、血管壁组织病理变化检测等。结果两组的血栓形成率差异无统计学意义(P>0.05)。在4周的观察期内,代表增殖的PCNA蛋白印迹条带显示:实验组移植静脉、吻合口的浓度较对照组低。术后1、2、3及4周,实验组移植静脉PCNA阳性细胞指数分别为0.13%±0.11%,0.79%±0.28%,0.45%±0.29%,0.43%±0.25%,吻合口分别为1.90%±0.84%,2.11%±0.98%,2.48%±0.77%,2.17%±0.36%,较对照组明显减少(P<0.05);实验组移植静脉及吻合口的空腔面积分别为88.71±16.96、95.98±21.44、88.48±32.81、97.86±34.11μm2和41.49±3.34、45.15±11.65、46.27±8.90、51.62±8.85μm2,均较对照组大(P<0.05),实验组移植静脉、吻合口的内膜面积/中膜面积分别为22.73%±3.11%、32.40%±4.55%、45.14%±3.19%、45.70%±5.01%和41.49%±3.34%、45.15%±11.65%、46.27%±8.90%、51.62%±8.85%,均较对照组小(P<0.05)。最大血流速度比较,两组在第1周血流最大速度相似,后3周出现不同变化。对照组静脉移植段和吻合口的最大流速逐渐增加,在第3周达到最高,至第4周时降低;实验组静脉移植段和吻合口最大流速逐渐降低,在第3周达到最低,至第4周时升高。第4周实验组和对照组移植静脉段和吻合口最大流速均接近。各时间点两组内比较差异有统计学意义(P<0.05),组间比较差异无统计学意义(P>0.05)。结论壳聚糖纳米粒子携带PCNA-ASODN能有效抑制血管移植后内膜细胞增殖,从而抑制新生内膜过度增厚。     

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.