血管外膜和胶原分布对内膜增生及血管重塑的影响

目的 动态观察移植静脉再狭窄动物模型中血管外膜和胶原的变化,以评价血管外膜和胶原对内膜增生和血管重塑的影响. 方法 长白猪18只,建立猪移植静脉再狭窄模型,术后随机分为3组,术后7d组,术后30d组和术后45d组,每组6只;未移植前的大隐静脉作为对照组.采用HE和Masson染色,观察各组血管成分结构、外膜细胞密度、增生指数和胶原的动态变化. 结果 术后7d组新生内膜形成并增厚,外膜厚度和细胞密度增大,外膜和新生内膜中胶原增多,血管腔面积减少,但与对照组比较差异无统计学意义(F=2.03,P=0.091),而剩余狭窄率逐渐增大(F=5.16,P=0.033),重塑指数和外弹力板围绕面积(EELA)稍有增大.术后30d组新生内膜明显增厚,外膜厚度和细胞密度达最大,新生内膜中含大量胶原,呈进行性增多趋势,外膜中胶原含量达最大,管腔面积和内膜弹力板围绕面积(IELA)明显减小,剩余狭窄率较对照组明显增大(F=6.63,P=0.018),重塑指数和EELA较术后7d组明显减小.术后45d组新生内膜增厚达最大,外膜细胞密度较术后30d组减小(F=6.91,P=0.015),新生内膜中胶原含量达最大,外膜中胶原含量较术后30d组减少,并见局部纤维化;管腔面积、重塑指数、IELA和EELA达最小,剩余狭窄率达最大. 结论 移植血管再狭窄是内膜增生和血管重塑共同作用的结果 .血管外膜的增厚、纤维化及胶原的重排对内膜增生和血管重塑起着重要作用,参与并促进了移植血管再狭窄的发生过程.     

MMP-2、MMP-9、TIMP-1在血管成形术后再狭窄中的表达及其意义的实验研究

目的观察PTA后MMP-2、MMP-9和TIMP-1在血管壁各层随时间的演变规律,探讨其在血管再狭窄过程中的表达及意义。方法48只大鼠制作成颈动脉再狭窄动物模型,选取30只内膜增生满意的标本,分别代表动脉损伤后1、3、7、14、28、42天6个观察时间点,对胶原纤维进行Masson染色。MMP-2、TIMP-1、PCNA进行免疫组织化学染色,MMP-9进行免疫组织化学和原位杂交两种染色。分析它们的表达与内膜增生和血管重塑的关系。结果正常血管不表达MMP-9mRNA及蛋白,损伤后第3天中膜、外膜mRNA表达达高峰,第7天内膜表达达高峰。MMP-9蛋白第7天内膜表达达高峰,且阳性细胞率高于中膜和外膜。第14、28天,血管壁各层表达逐渐下降至基线水平,内膜的阳性细胞主要集中在新生内膜靠近管腔的一侧。内膜MMP-2表达高峰出现晚至第14天,且近内弹力板处MMP-2也有明显的表达。正常血管壁不表达TIMP-1,损伤后第3天,中膜和外膜表达达高峰。第7天,新生内膜表达达高峰,中膜和外膜仍有较高水平表达。结论MMP-9、MMP-2、TIMP-1参与再狭窄,内膜MMP-9表达与早期增殖的细胞向内膜迁移形成新生内膜有关。MMP-2表达与晚期内膜形成、内膜重塑有关。TIMP-1的表达对内膜增生和重塑没有直接作用,其表达升高是机体为适应MMPs升高做出的代偿反应,在维持自身平衡中起作用。     

去势对雄性大鼠血管成形术后再狭窄的影响

目的 :系统观察血管外膜细胞在血管成形术 (PTA)后再狭窄过程中的动态变化 ,通过复制去势模型对照观察雄激素对再狭窄的影响 ,并探讨其作用机制。　方法 :复制雄性SD大鼠的去势模型及颈总动脉再狭窄模型 ,于术后 3、7、14、2 8d不同时间点取材 ,行苏木精 伊红染色及免疫组化染色 ,并以电镜观察血管狭窄情况。　结果 :PTA术后 3d增殖细胞首先出现在血管外膜 ,并发生表型转变 ,术后 7d时外膜细胞增殖最明显 ,并向内膜迁移 ,术后 14d外膜细胞增殖减少 ,增殖细胞集中于中膜及新生内膜。各观察时间点 ,去势雄性大鼠的血管外膜面积、新生内膜面积、血管狭窄程度 ,均较未去势组大。以 14d组为例 ,血管外膜面积 [(35 6 6± 337) μm2 vs (2 75 1± 4 0 1) μm2 ,P =0 .0 0 8],新生内膜面积 [(35 5 3± 4 77) μm2 vs (2 75 7± 4 35 ) μm2 ,P =0 .0 2 5 ],血管狭窄程度 [(76± 2 ) %vs (6 0±8) % ,P =0 .0 0 5 ],外膜细胞增殖指数 [(2 9± 2 ) %vs (13± 1) % ,P <0 .0 0 1]。　结论 :PTA术后血管外膜细胞增殖、迁移参与了再狭窄的形成。生理状态下体内雄激素可以减轻血管再狭窄程度 ,其作用机制可能与干预血管外膜细胞活化有关。     

STAT3信号通路与血管重塑中平滑肌细胞表型转化及增殖关系

目的 观察静脉桥再狭窄模型中血管平滑肌细胞(VSMC)表型转化和增殖活性的变化,探讨信号转导子和激活子3蛋白(STAT3)的表达与VSMC表型转化及增殖活性的关系.方法 建立猪静脉桥再狭窄模型,采用血管病理形态学、免疫组织化学和免疫印迹(Western blot)方法,观察术后7、14、30 d血管蓖塑及血管壁中增殖细胞核抗原(PCNA)、平滑肌ot肌动蛋白(SM-α actin)和STAT3表达变化及其相关性.结果 (1)术后7 d新牛内膜形成逐渐增厚,于术后30 d达最大;重塑指数和外弹力板围绕面积(EELA)术后7 d稍有增大,其后不断减小,术后14～30 d明显减小(P<0.05).(2)免疫组织化学和Western blot测定STAT3蛋白显示,术后7 d中膜VSMC中阳性表达明显,术后14 d中膜VSMC和内膜VSMC中阳性表达均增加达高峰;术后30 d中膜VSMC中有较少部分阳性表达,内膜VSMC中阳性表达较14 d减少.血管中膜中STAT3和PCNA的蛋白呈显著性正相关(r=0.726,P<0.05).结论 血管平滑肌细胞的表型转化和增殖活性改变对内膜增生和血管重塑起着重要作用,STAT3信号通路与血管重塑中VSMC的增殖高度相关,参与并促进了VSMC的表型转化和增殖.     

卡托普利对血管成形术后再狭窄作用的实验研究

目的探讨卡托普利对血管成形术后再狭窄的干预作用。方法SD雄性大鼠60只,分单损组、干预组和对照组。单损组采用改良导丝法制作大鼠颈动脉再狭窄模型。干预组将卡托普利研磨成粉状,生理盐水稀释配制成5mg/ml溶液,分别于制模前6 d开始按10 mg/(kg.d)剂量经灌胃针给予大鼠至术后各时间点。对侧颈总动脉作为假手术对照组。每组各时间点6只大鼠,于制模后1天、4天、7天、14天及28天原位灌注固定取材。根据HE染色标本情况,选血管形态结构完整的50个标本,进行HE染色,采用病理图像分析系统染色片进行形态计量分析。结果损伤后从第7天起新生内膜厚度和面积逐渐增加,到28天达峰值;与单损组比较,干预组血管壁三层厚度无显著差别,干预组第14、28天新生内膜面积显著减低。狭窄率于血管损伤后逐渐增加,到28天达峰值,与单损组比较,干预组在14天和28天狭窄率明显变小,各时间点内弹力板面积、外弹力板面积及重塑指数两组之间无显著差别。结论卡托普利减小大鼠颈动脉损伤后新生内膜面积及狭窄率,抑制新生内膜形成,但不改变内、外弹力板面积及重塑指数,不影响血管收缩性重塑。     

血管壁重塑与平滑肌细胞表型改变及调亡的研究

目的 研究血管平滑肌细胞(VSMC)表型改变和调亡与血管壁重塑的关系。方法 建立兔髂动脉粥样硬化再狭窄模型，分析再狭窄血管壁形态和结构变化，研究中膜、内膜VSMC的表型改变，检测各个时间段内膜和中膜层VSMC调亡。结果 再狭窄血管腔面积与血管壁重塑指数呈正相关(r＝0．9250，P＝0．0024)，再狭窄血管的管径较对侧明显缩小(P＝0．0001)。中膜VSMC表型主要以收缩型表型为主，血管壁内膜的VSMC的表型发生动态变化。中膜与内膜VSMC调亡峰值基本一致，中膜VSMC调亡指数明显高于内膜(P＝0．0061)。结论 血管壁重塑在血管重建再狭窄中起着重要的作用，在血管壁重塑过程中调控VSMC的表型转化和调亡可能控制血管壁的不适重塑，减少再狭窄的发生率。     

血管成形术后再狭窄中细胞增殖与凋亡的研究

目的　动态观察血管成形术后不同时间段增生内膜细胞凋亡、增殖的变化过程。方法　将新西兰大白兔 35只随机分成 7组 ,应用 2次损伤法建立兔髂动脉再狭窄模型 ,检测血管成形术后 5 6d内 7个不同时间段 ( 0、3、7、14、2 8、42、5 6d)增生内膜的细胞增殖、凋亡指数及内膜面积、内膜细胞数。结果　血管成形术后内膜细胞凋亡与增殖的变化并不是同步的 ,术后第 7天凋亡指数达到高峰 ,为 ( 2 2 .81± 4.19) % ,增殖指数在术后第 14～ 2 8天最高 ,但峰值较低 ,分别为( 16 .2 1± 1.78) %、( 15 .49± 1.6 1) %。结论　内膜细胞增殖与凋亡的失衡是决定再狭窄的重要因素。     

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。     

尿激酶型纤溶酶原激活物及其受体高表达增强血管收缩性重塑和内膜增生的研究

目的　探讨血管壁中尿激酶型纤溶酶原激活物 (uPA)和其受体 (uPAR)表达与血管收缩性重塑和内膜增生的相关性。方法　建立兔髂动脉粥样硬化再狭窄模型 ,比较内膜和中膜层的uPA、uPAR表达及其与内膜面积和血管重塑指数的相关性。结果　内膜层uPA、uPAR的抗原和mRNA表达明显强于中膜层 (P <0 .0 1) ,血管壁内膜uPA、uPAR的抗原和mRNA表达水平与血管重塑指数呈负相关 (r =-0 .870 0 7,P =0 .0 10 9;r =-0 .860 3 8,P =0 .0 13 0和r =-0 .845 5 5 ,P =0 .0 165 ,r =-0 .862 40 ,P =0 .0 12 5 ) ,与内膜面积呈正相关 (r=0 .92 0 0 0 ,P =0 .0 3 3 0 ;r=0 .90 772 ,P =0 .0 0 47和r=0 .92 14 9,P =0 .0 0 3 2 ;r =0 .90 614 ,P =0 .0 0 49) ,血管重塑指数和血管内膜面积与中膜uPA、uPAR表达无明显相关性。结论　内膜层uPA、uPAR高表达增强了血管重建后血管壁收缩性重塑和内膜增生。     

颈动脉内膜切除术后细胞凋亡对早期再狭窄的影响

目的 探讨颈动脉内膜切除术（CEA）后新内膜形成过程中细胞凋亡对早期再狭窄的影响。方法 以新西兰兔颈动脉粥样硬化性狭窄动物模型为基础，分别采用免疫组织化学方法及原位末端标记（TUNEL）法观察颈动脉内膜切除术后不同时间点新内膜中Bax、Bcl-2动态表达及细胞凋亡的过程。结果 Bax、Bcl-2在正常动脉壁无表达。Bcl-2于术后3d内膜开始表达，术后30d达到高峰，随后逐渐下降。Bax于术后3d内膜开始表达，术后7d到达高峰，随后逐渐下降，Bcl-2／Bax的比值在术后30d达峰值。新内膜中细胞凋亡则在早期再狭窄的后期90d达峰值。结论 新内膜中细胞凋亡处于较活跃的水平，细胞凋亡在CEA术后早期再狭窄形成过程中有重要作用。     

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.