细胞外信号调节激酶和P38蛋白激酶在自体移植静脉中的表达

目的研究丝裂原活化蛋白激酶亚单位细胞外信号调节激酶(ERK)和p38蛋白激酶(p38 MAPK)在移植静脉血管重塑过程中的表达.方法选Wistar大鼠80只,建立自体移植静脉模型,术后随机分为6 h、24 h、3 d、7 d、2周、4周、6周及8周组,于相应时点取材,半定量逆转录PCR法检测移植血管中ERK和p38 MAPK的mRNA表达;Western蛋白印迹定量检测ERK和p38 MAPK的蛋白产物及磷酸化蛋白产物表达;脱氧核苷酸末端转移酶末端标记法(TUNEL)检测血管平滑肌细胞(VSMC)凋亡的变化;免疫组化检测增殖细胞核抗原(PCNA)的表达.结果移植静脉术后6 h,ERK1和p38 MAPK的mRNA表达均明显增强,与正常静脉组比较差异均有显著性意义(P＜0.01);ERK1mRNA表达在移植后7 d达高峰,表达值为(33.2±14.2)%,p38 MAPK的mRNA表达于术后2周达到高峰,表达值为(58.8±26.2)%,与其余各时点比较差异有显著性意义(P＜0.01).Western蛋白印迹提示ERK1/2在术后1～2周达高峰,6周时逐渐恢复至正常水平;而p38 MAPK则在移植后2～4周达高峰,之后开始减少,8周时仍维持一定表达量(1/4～1/2).ERK1与PCNA表达呈正相关(r=0.759 6,P＜0.01),p38 MAPK与凋亡呈正相关(r=0.892 2,P＜0.01).结论MAPK的激活是移植静脉内膜增生以及血管重塑的关键环节,可能成为防治移植静脉狭窄、闭塞的新的治疗靶点.     

mTOR信号转导通路在自体移植静脉中的表达及意义

目的研究哺乳类动物雷帕霉素靶蛋白(mTOR)在自体移植静脉中表达的动态变化规律。方法Wistar大鼠64只,建立自体静脉移植模型,随机分为8组,分别在移植后6 h,1、3 d,1、2、4、6、8周切取移植静脉。逆转录PCR结合原位杂交研究移植血管中mTOR的tuRNA表达,Western blot联合免疫组化检测mTOR蛋白产物表达的变化,同时检测增殖细胞核抗原(PCNA)。结果逆转录PCR扩增在静脉移植1-3 d即出现mTOR mRNA表达增强,1-2周达到高峰,表达值分别为(48±18)％和(33±11)％,与其他组比较差异有统计学意义(P<0．01),6-8周逐渐恢复正常。免疫组化及Western蛋白印迹均提示mTOR蛋白在移植3 d表达明显增多,2-4周达到高峰,分别为(29±8)％和(31±6)％,与其他组比较差异有统计学意义(P<0．01),8周恢复至正常水平。mTOR蛋白产物表达与PCNA表达呈正相关(r=0．756,P<0．01)。结论mTOR在血管移植后的过程中被激活,与内膜增生关系密切,可能是防治移植血管狭窄、闭塞的干预靶点。     

p38 MAPK在自体移植静脉中的表达及其意义

目的　研究丝裂原活化蛋白激酶p3 8MAPK信号传导通路在自体移植静脉中的表达。方法　Wistar大鼠 80只 ,建立自体移植静脉模型。术后随机分为 6,2 4h ,3 ,7d和 2 ,4,6,8周等 8组 ,于相应时点取材 ,半定量逆转录PCR检测移植血管中p3 8MAPK的mRNA表达 ,Western蛋白印迹定量检测 p3 8的蛋白产物及磷酸化蛋白产物表达 ,原位杂交和免疫组化方法定位p3 8mRNA及蛋白表达。结果　移植静脉术后 6hp3 8的mRNA表达即较正常静脉明显增强 (P <0 .0 1) ,并于术后 2周达高峰 ,表达值为 (59± 2 6) % ,与 4,6,8周比较差异极显著 (P <0 .0 1)。Western蛋白印迹提示 p3 8在移植 2～ 4周达高峰 ,之后开始减少 ,8周时仍维持一定表达量 (1/4～ 1/2 )。原位杂交及免疫组化提示阳性表达多定位于移植血管中层或增生内膜中的血管平滑肌细胞 (VSMCs)。结论　p3 8MAPK通路的激活参与了移植静脉的内膜增生以及血管重塑 ,可望成为防治移植静脉狭窄闭塞的治疗靶点     

雷帕霉素靶蛋白及其底物在自体移植静脉中的表达及意义

目的研究雷帕霉素靶蛋白（mammalian target of rapamycin,mTOR）及其底物——核糖体蛋白s6激酶（p70s6k）、真核细胞启动子4E结合蛋白1（4E—BP1）在自体移植静脉中表达的动态变化规律,探讨其与内膜增生的关系及意义。方法Wistar大鼠64只,建立自体静脉移植模型,随机分为8组,分别在移植后6h,1、3d,1、2…468周切取移植静脉。逆转录-聚合酶链反应（RT—PCR）联合原位杂交方法检测移植血管中mTOR及其底物pT0s6k和4E—BPI的mRNA表达,Western蛋白印迹或免疫组化方法检测mTOR、pT0s6k和4E—BP1的蛋白产物表达,同时检测增殖细胞核抗原（PCNA）的表达。结果静脉移植1—3d即出现mTOR和pT0s6k的mRNA表达增强,3d-2周达到高峰,与其他组比较差异有统计学意义（P〈0．01）,6—8周逐渐恢复正常;而4E—BP1的mRNA表达在移植后1d开始降低,1周表达最低,之后表达开始增强,4～6周为表达高峰,与其他组比较差异有统计学意义（P〈0．01）。Western蛋白印迹提示mTOR和pT0s6k蛋白产物在移植后1周表达明显增加,2～4周达到高峰,8周恢复至正常水平;而4E—BP1蛋白产物在移植后1周表达最少,4—6周增加达到高峰,8周仍维持一定的表达量。原位杂交及免疫组化结果提示阳性细胞多定位于移植静脉新生内膜和中膜血管平滑肌细胞,mTOR及其底物与PCNA分布基本一致。结论mTOR信号通路在血管移植后即被激活并与内膜增生关系密切,可能成为防治移植血管狭窄、闭塞的有效靶点。     

Egr-1DNA酶抑制自体移植静脉内膜增生的实验研究

目的 探讨早期生长反应基因-1 (Egr-1) DNA酶(Egr-1 DNA enzyme,EDRz)对血管平滑肌细胞(VSMC)增殖和内膜增生的抑制作用,从而证实基因治疗静脉移植后狭窄、闭塞的可行性.方法 构建EDRz,建立自体静脉移植模型,将大鼠右颈总静脉端-端吻合于肾下腹主动脉,EDRz转染移植静脉,分别于移植后1、2、6、24 h及3、7、14、28、42 d切取移植静脉标本,每个时相按随机数字表法随机抽取10只大鼠.荧光显微镜下观察EDRz转染移植静脉情况;应用原位杂交和RT-PCR方法检测Egr-1 mRNA的表达;应用Western蛋白印迹和免疫组织化学方法检测Egr-1蛋白表达情况;HE染色光镜下观察组织学形态.结果 ①EDRz转染移植静脉情况:移植后1h时,EDRz主要位于移植静脉的外膜、中膜和部分内皮细胞;2、6及24 h时,EDRz则主要位于移植静脉的中膜;7d时,EDRz主要位于移植静脉的内膜; 14、28及42 d时未检测到EDRz的表达.②Egr-1 mRNA表达结果.RT-PCR检测结果:转染EDRz后1h时,Egr-1 mRNA表达出现高峰,2、6及24 h表达下降,3d时表达微弱,移植后7、14、28及42 d未见Egr-1 mRNA的表达,转染EDRz后1h时Egr-1 mRNA表达明显高于其余各时相(P＜0.01).原位杂交检测Egr-1 mRNA表达的变化趋势与RT-PCR结果基本一致.③Egr-1蛋白表达结果.Western蛋白印迹结果:正常静脉中未检测到Egr-1蛋白阳性表达.转染EDRz后2h时,出现Egr-1蛋白阳性表达,6h、24 h及3d时其表达逐渐降低,移植后1h时和移植后7、14、28及42 d时未见Egr-1蛋白阳性表达.移植后2h时的Egr-1蛋白表达的吸光度值高于其他时相(P＜0.01).免疫组织化学方法检测的Egr1蛋白阳性表达的变化趋势与Western蛋白印迹结果基本一致.④EDRz转染移植静脉与未转染同期相比VSMC的增殖程度和内膜厚度明显减轻.结论 EDRz通过减少Egr1在自体移植静脉中的表达,可有效地抑制自体移植静脉中VSMC增殖和内膜增生,可用来防治自体静脉移植后所导致的血管狭窄、闭塞.     

细胞间粘附分子-1在自体移植静脉中表达的动态变化

目的　研究细胞间粘附分子 (ICAM ) 1在自体移植静脉中表达的动态变化规律 ,探讨其与内膜增生的关系及意义。方法　Wistar大鼠 5 6只 ,建立自体静脉移植模型 ,随机分为 7组 ,分别在移植后 1、3d ,1、2、4、6、8周切取移植静脉。半定量逆转录 聚合酶链反应 (RT PCR)结合原位杂交定位研究移植血管中ICAM 1mRNA的表达 ,Westernblot联合免疫组织化学方法检测I CAM 1蛋白产物表达的变化。结果　ICAM 1mRNART PCR扩增见静脉移植 1～ 3d即出现表达增强 ,1～ 2周达到高峰 ,表达值分别为 ( 3 6.6± 12 .9) %和 ( 5 8.7± 11.1) % ,与其他组比较差异有显著性 (P <0 .0 1) ,6～ 8周逐渐恢复正常 ,与原位杂交变化趋势基本一致。免疫组织化学结果见I CAM 1在移植 1～ 7d表达明显增多 ,2～ 4周达到高峰 ,分别为 ( 2 3 .5± 7.1) %和 ( 2 0 .6± 9.2 ) % ,与其他组比较差异有显著性 (P <0 .0 1) ,8周恢复至正常水平 ,与Western蛋白印迹结果一致。结论ICAM 1与移植静脉内膜增生关系密切 ,可能成为防治内膜增生以及血管移植后狭窄闭塞一个新的治疗靶点。     

JNK、p38 MAPK在移植静脉血管重塑过程中的表达研究

目的　研究c Jun氨基末端激酶 (JNK)和p38蛋白激酶 (MAPK)在移植静脉血管重塑过程中的表达。方法　Wistar大鼠 80只 ,建立自体移植静脉模型 ,术后随机分为 6h ,1、3、7,1 4、2 8、4 2、5 6d等 8组 ,于相应时点取材 ,逆转录聚合酶链反应 (RT PCR)检测JNK和p38MAPK的mRNA表达 ,Western蛋白印迹检测JNK和p38的蛋白产物及磷酸化蛋白产物表达 ,原位杂交和免疫组化方法定位mRNA及蛋白产物表达 ,脱氧核苷酸转移酶末端标记法 (TUNEL)检测血管平滑肌细胞 (VSMC)凋亡的变化。结果　移植静脉术后 6h ,JNK和p38的mRNA表达增强 ,在术后 1 4d达到高峰 ,表达值分别为(2 6± 1 0 ) %和 (5 9± 2 6 ) %,与各时点比较差异有统计学意义 (P <0. 0 1 )。JNK、p38的蛋白产物表达在1 4～ 2 8d达高峰 ,在 5 6d时仍维持一定表达量 (1 .4～ 1 . 2 )。原位杂交及免疫组化提示阳性表达多位于移植血管中层或增生内膜中的血管平滑肌细胞 (VSMC) ,p38与凋亡呈正相关 (r =0 . 892 2 ,P <0. 0 1 )。结论　JNK和p38MAPK通路的激活是移植静脉内膜增生以及血管重塑的关键环节 ,可能成为新的治疗靶点。     

金属蛋白酶1组织抑制因子在大鼠自体移植静脉中的表达研究

目的 研究金属蛋白酶1组织抑制因子(tissue inhibitor of metalloproteinase-1,TIMP-1)在大鼠自体移植静脉血管平滑肌细胞中的表达和动态变化的意义.方法 建立大鼠自体血管移植模型,移植后不同时间分别切取移植静脉,应用HE染色、免疫组织化学和原位杂交方法动态观察TIMP-1的表达和变化情况.结果 移植血管组织病理学改变:血管移植后1周可见内膜增生(intimal hyperplasia:IH),2～4周达到高峰.原位杂交结果:TIMP-1mRNA在移植后24 h出现细胞阳性表达,72 h阳性表达明显增多,1-2周时表达达到高峰,与移植后1 d相比,差异有统计学意义(P<0.01).免疫组织化学染色:静脉移植后72 h出现TIMP-1的表达,1周时增加明显,2周时表达最强,与移植后1 d相比,差异有统计学意义(P<0.01).结论 在自体移植静脉中存在TIMP-1的激活.自体静脉移植于动脉后,内源性TIMP-1的分泌增加不足以抑制内膜增生.     

Egr-1在自体移植静脉中的表达及意义

目的研究自体静脉移植后早期生长反应基因-1(Egr-1)表达的动态变化,探讨其在内膜增生中的作用。方法Wistar大鼠90只,将大鼠右颈总静脉端-端吻合于肾下腹主动脉建立自体静脉移植模型。术后随机分别于1、2、6和24h,3、7、14、28及42d相应时间处死动物取移植静脉,同时取正常静脉作对照。应用原位杂交和RT-PCR方法检测Egr-1mRNA的表达,联合应用Western蛋白印迹和免疫组织化学方法检测Egr-1蛋白表达情况,同时进行组织形态学观察。结果自体静脉移植后,Egr-1mRNA和Egr-1蛋白的表达呈双相变化,即移植后1h,Egr-1mRNA表达迅速升高,阳性率为(35±7)%,6h、24h及3d时下降到较低水平,阳性率分别为(8±2)%、(8±6)%和(8±4)%,7d时又再升高,28d时达高峰,阳性率为(45±6)%,此与其余各时点比较差异均有统计学意义(P<0.01),42d时,Egr-1mRNA的表达再次下降;移植早期(2h)即有Egr-1蛋白的表达,阳性率为(30±5)%,并持续至6h,24h~3d表达下降到较低水平,阳性率分别为(7±3)%和(7±8)%,7d时又再升高,至移植后28d,Egr-1蛋白的表达阳性率达到高峰,为(40±9)%,此与其余各时点比较差异有统计学意义(P<0.01)。移植后7d,免疫组化结果显示,Egr-1蛋白表达主要位于中膜血管平滑肌细胞(VSMCs)和单核细胞/巨噬细胞,移植后期28d,Egr-1蛋白表达主要位于新生内膜和中膜的VSMCs,同时部分内皮细胞也有Egr-1蛋白的表达。结论移植静脉内膜增生与Egr-1的激活及表达关系密切,Egr-1可能成为防治移植静脉内膜增生、狭窄及闭塞的一个新的干预靶点。     

内皮素、内皮素转化酶在自体静脉移植术后内膜增生中的作用

目的探讨内皮素 1(endothelin 1,ET 1)及内源性内皮素转化酶 (endothelinconvertingenzyme ,ECE)在自体静脉移植术后内膜增生中的作用。 方法建立自体静脉移植模型 ,采用反转录聚合酶链反应 (RT PCR)和免疫组织化学方法 ,对ECE、ET 1和增殖细胞核抗原 (proliferatingcellnuclearantigen ,PCNA)在移植静脉的表达情况进行分析。 结果移植术后 6h ,吻合口处静脉中膜即出现PCNA阳性平滑肌细胞 ,并随着时间推移逐渐增高 ,在 1～ 2周左右达到高峰。 2周后 ,PCNA阳性SMC开始减少 ,于术后 8周趋于平稳。移植血管ET 1、PCNA主要在平滑肌细胞中表达。在mRNA水平 ,随着移植术后时间的推移 ,ECE的表达逐渐增高 ,术后 1～ 2周达到高峰 ,在 8周左右趋于平稳 ,ET 1与ECE密切相关 (r =0 975 )。结论ET 1、ECE的动态变化过程具有相关性 ,ECE可能通过ECE→ET 1→SMC通路促进内膜增生。     

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.