基质细胞衍生因子联合外周血内皮祖细胞移植治疗裸鼠肢体缺血

目的 应用基质细胞衍生因子(SDF-1)结合外周血内皮祖细胞(EPCs)移植治疗裸鼠肢体缺血,探讨其促进血管新生的能力.方法 建立裸鼠后肢缺血模型,随机分为缺血对照组、EPCs移植组、SDF-1组、SDF-1联合EPCs移植组及SDF-1联合AMD3100处理后的EPCs移植组.移植第3、7天检测后肢腓肠肌CD34+VEGFR+细胞数,第28天检测缺血区新生血管密度.结果 移植第3天对照组、EPCs组、SDF-1组、SDF-1+EPCs组、SDF-1+AMD3100 EPCs组双阳性细胞数分别为0.00±0.00个/HP、5.30±0.65个/HP、0.00±0.00个/HP、10.31±0.63个/HP及1.86±0.17个/HP;第7天分别为0.00±0.00个/HP、7.05±0.18个/HP、0.00±0.00个/HP、11.81±0.53个/HP及2.83±0.48个/HP,第28天新生毛细血管数分别为3.00 ±0.13个/HP、6.15±0.04个/HP、6.20±0.10个/HP、10.65 ±0.08个/HP、6.21±0.08个/HP.SDF-1可增加缺血区CD34+ VEGFR+细胞浸润数量(P＜0.05),提高新生血管数量(P＜0.05),SDF-1联合外周血EPCs可进一步提高新生血管数量(P＜0.05).结论 SDF-1能够促进EPCs归巢,增强血管形成能力,促进血管新生;AMD3100能够阻断SDF-1的诱导迁移效应.

Abstract：

Objective To explore the effect of stromal cell-derived factor-1 ( SDF-1 ) in combination with transplantation of peripheral blood endothelial progenitor cells (EPCs) for the treatment of nude mice hindlimb ischemia. Methods Hindlimb ischemia model was established in nude mice, mice were then divided into five groups randomly: ischemic control group, peripheral blood EPCs transplantation group, SDF-1 local application group, SDF-1 combined with EPCs group, SDF-1 combined with AMD3100 treated EPCs group. Local CD34+VEGFR+ cells in the hind gastrocnemius were detected at day 3,7 after transplantation. The intensity of neovasculorization were evaluated at day 28. Results The double-positive cells number of control group, EPCs group, SDF-1 group, SDF-1 + EPCs group, SDF-1 + AMD3100 EPCs group were 0.00 ±0.00,5. 30 ±0.65,0.00 ±0.00,10. 31 ±0. 63,1. 86 ±0. 17 at day 3 and 0. 00 ±0. 00, 7.05 ±0. 18,0. 00 ±0. 00,11. 81 ±0. 53,2. 83 ±0. 48 at day 7. The number of new capillaries were 3. 00 ± 0.13,6.15 ± 0. 04,6. 20 ± 0. 10,10. 65 ± 0.08,6. 21 ±0. 08 at day 28. SDF-1 increased the CD34 + VEGFR+ cells (P ＜0. 05) and the number of new vessels (P ＜0.05). SDF-1 combined EPCs further increased the number of new vessels (P ＜ 0. 05 ). Conclusions SDF-1 enhances blood vessel formation and promotes angiogenesis by promoting EPCs homing, which could be blocked by AMD3100.     

自体骨髓CD34+干细胞移植治疗严重肢体缺血的实验研究

目的探讨自体骨髓干细胞移植是否能增加缺血肢体的新生血管形成。方法抽取5只犬骨髓20ml,经Ficoll分离单核细胞,免疫磁珠分离CD34+细胞,在体外经血管内皮细胞生长因子诱导分化为内皮细胞,并经vWF抗染色鉴定。建立犬双侧肢体缺血动物模型,将Dil荧光标记的内皮细胞植入缺血肢体中。结果CD34+干细胞移植4周后,激光共聚焦显微镜证实缺血肢体中移植的自体骨髓干细胞参与了新生血管形成;动脉造影见干细胞移植的肢体侧枝循环明显增加,微血管密度检测移植组也明显高于对照组(12.0±2.8vs.5.0±1.6/每高倍镜视野,t=4.17,P<0.05);干细胞移植的肢体ABI平均为0.58±0.14,对照肢体ABI平均为0.32±0.11,差异有统计学意义(t=2.95,P<0.05)。结论自体骨髓干细胞移植能有效的促进缺血组织内的新生血管形成。     

骨髓基质细胞移植于缺血心肌的研究

国家自然科学基金资助项目 ( 30 170 935)目的　研究骨髓基质细胞移植于缺血心肌后的分化增殖情况和对心功能的保护作用。方法　以同基因背景的Lewis大鼠为研究对象 ,将溴氮胞苷 (BrdU)标记的骨髓基质细胞移植于结扎冠状动脉的大鼠缺血心肌内 ,4周后观察移植细胞的分化增殖情况和促血管生长作用 ,并用超声检测心功能改变。结果　细胞移植 4周后 ,可以在缺血心肌内找到BrdU标记的移植细胞 ,其中相当一部分细胞已分化为肌浆球蛋白重链 (MHC)阳性的心肌细胞。另外IIIV因子染色可见实验组移植区内有大量的血管新生 (2 3± 4/HPF) ,而对照组中却很少发现 (2± 1 /HPF) ,差异有非常显著性 (P <0 .0 1 )。超声检查显示移植骨髓基质细胞后可显著改善缺血心脏功能 ,其中实验组动物射血分数 (EF)升高了 0 .2 51± 0 .1 0 3 ,而对照组却降低了 0 .0 94± 0 .0 0 3 ,差异有非常显著性 (P<0 .0 1 )。结论　骨髓基质细胞移植于缺血心肌后可以向心肌细胞转化 ,并可明显改善心肌功能     

自体骨髓CD34+干细胞移植治疗严重肢体缺血的实验研究

目的探讨自体骨髓干细胞移植是否能增加缺血肢体的新生血管形成.方法抽取5只犬骨髓20 ml,经Ficoll分离单核细胞,免疫磁珠分离CD34+细胞,在体外经血管内皮细胞生长因子诱导分化为内皮细胞,并经vWF抗染色鉴定.建立犬双侧肢体缺血动物模型,将Dil荧光标记的内皮细胞植入缺血肢体中.结果 CD34+干细胞移植4周后,激光共聚焦显微镜证实缺血肢体中移植的自体骨髓干细胞参与了新生血管形成;动脉造影见干细胞移植的肢体侧枝循环明显增加,微血管密度检测移植组也明显高于对照组(12.0±2.8 vs. 5.0±1.6/每高倍镜视野,t=4.17, P<0.05);干细胞移植的肢体ABI平均为0.58±0.14,对照肢体ABI平均为0.32±0.11,差异有统计学意义(t=2.95, P<0.05).结论自体骨髓干细胞移植能有效的促进缺血组织内的新生血管形成.     

血管内皮祖细胞移植提高裸鼠缺血皮瓣存活率

目的探讨血管内皮祖细胞(endothelialprogenitorcell,EPC)移植促进早期断蒂的缺血皮瓣的血管新生,从而提高皮瓣存活率的可能性。方法体外分离、培养人脐血中EPCs,免疫组织化学进行鉴定,然后移植于裸鼠随意皮瓣,皮瓣早期断蒂,裸鼠分两组:实验组(EPCs移植)、对照组(M199注射),术后皮瓣4d断蒂。观察皮瓣的存活率、激光多普勒血液监测仪监测血流灌注、CD34免疫组织化学检测皮瓣毛细血管密度、激光共聚焦检测EPCs在皮瓣内的密度。结果脐血中分离培养的EPCs表达CD34、KDR及CD133,实验组EPCs移植裸鼠皮瓣后,整合到缺血部位新生血管中,与对照组的皮瓣存活率分别为(60.3±2.1)%、(34.2±1.8)%(P<0.05);而且两组毛细血管密度、血流灌注差异均有统计学意义(P<0.05);实验组术后第7、11天时二组皮瓣中的EPCs密度分别为(75.2±6.5)个/mm2、(305.4±26.5)个/mm2,而对照组均为0个/mm2(P<0.05)。结论脐血中的EPCs体外培养后移植体内可促进缺血皮瓣的血管新生,提高存活率。     

血管内皮细胞生长因子基因转染血管内皮祖细胞移植提高移植脂肪存活率的实验研究

目的探讨血管内皮细胞生长因子165(VEGF165)基因转染血管内皮祖细胞(EPCs)移植促进游离移植的脂肪组织的血管新生,提高移植脂肪组织存活率。方法体外分离、培养人脐血中EPCs,利用脂质体介导VEGF165基因体外转染EPCs,然后与来自人体的脂肪组织混合移植于裸鼠背部,裸鼠随机分为3组:VEGF165基因转染组、EPCs组及M199培养基对照组。结果脐血中分离培养的EPCs表达CD34、血管内皮细胞生长因子受体及CD133;VEGF165基因转染EPCs体外及体内检测均有VEGF165蛋白的表达。VEGF165基因转染组、EPCs组中,EPCs整合到缺血部位新生血管中,与对照组的脂肪组织存活率分别为(96.2±8.6)%、(75.3±6.8)%和(40.2±2.5)%(P<0.05),VEGF165基因转染组与EPCs组脂肪组织周边区毛细血管密度有显著差异(P<0.05),均高于对照组(P<0.05)。术后3个月时3组脂肪组织周边区的EPCs密度分别为(196±16)个/mm2、(95±11)个/mm2、0个/mm2(P<0.05)。结论脐血中的EPCs体外培养后移植体内可促进游离移植的脂肪组织的血管新生,提高存活率,而转染VEGF165基因的EPCs具有更强的促血管新生的作用。     

自体干细胞移植治疗兔后肢缺血中超顺磁氧化铁纳米颗粒标记磁共振体内示踪的研究

目的探讨自体骨髓间充质干细胞（BMSC）移植治疗兔后肢缺血中超顺磁氧化铁纳米颗粒（SPION）标记磁共振成像（MRI）体内示踪的可行性和有效性。方法新西兰大白兔14只，分成A、B两组，各7只。制作后肢缺血模型。A组移植SPION与5-溴脱氧尿嘧啶（BrdU）共标记的自体BMSC；B组作为对照。术后MRI示踪，组织学检查，免疫组织化学染色。结果鉴定显示BMSCCD34和CIM5阴性，CD44阳性。B组中1只死亡。A组毛细血管密度198．9±2．3，B组80．5±5．1．A组毛细血管／肌纤维比值0．84±0．03，B组0．35±0．04，两组差异均有统计学意义（P〈0．01）。A组：电镜发现血管内皮细胞胞质内含SPION；对应部位组织切片血管壁细胞普鲁士兰铁染色、BrdU和CD34染色均阳性；MRI显示术后即时A组注射部位圆形低信号影，术后1—3周向周围扩散，部位与组织学检查结果一致。B组仅能见到普鲁士兰阳性颗粒游离于组织间隙，并非位于血管内皮细胞；MRI低信号影局限于注射局部，无扩散。结论自体BMSC移植治疗兔后肢缺血中SPION标记MRJ体内示踪可行、有效。     

犬自体骨髓干细胞在缺血肢体中新生血管形成中的作用

目的:探讨犬自体骨髓干细胞在缺血组织的新生血管形成中的作用.方法:抽取犬骨髓,经免疫磁珠系统分离出CD 34细胞,体外扩增并向血管内皮细胞诱导分化;建立犬双下肢缺血动物模型,将诱导分化细胞移植入一侧缺血肢体中作为实验组,另一侧缺血肢体植入等体积的生理盐水作为自体对照组.移植后6周,检测缺血肢体中新生血管的形成.结果:细胞移植后6周,动脉造影显示实验组缺血肢体侧枝循环增加,明显多于对照组.微血管密度检测实验组为(14±2.3)个/高倍镜视野,明显高于对照组(6±2.1)个/高倍镜视野(P<0.05).激光共聚焦显微镜证实缺血肢体中移植的自体骨髓干细胞参与了新生血管形成.结论:自体骨髓干细胞移植可以促进缺血肢体组织中的新生血管形成.     

血红素氧合酶1基因转移对大鼠肾缺血再灌注损伤的防护作用

目的探讨血红素氧合酶1(HO-1)基因转移对大鼠自体移植肾缺血再灌注损伤的保护作用。方法构建HO-1腺病毒表达载体,经肾动脉灌注转染26只大鼠(实验组)移植肾,4℃保存24h后行自体移植,移植后5d切除对侧肾脏;以25只大鼠为对照。于移植后3h、3d,应用逆转录聚合酶链反应(RT-PCR)及免疫组织化学方法检测移植肾HO-1基因及蛋白的表达;应用酶联免疫吸附试验(ELISA)法测定肾组织匀浆中HO-1蛋白的含量(以吸光度值表示)。结果移植后3h及3d,实验组移植肾HO-1mRNA的表达强度分别为0·65±0·11及0·86±0·17,而对照组分别为0·09±0·01及0·15±0·02,两组相比差异具有统计学意义(t=14·38,11·73,P均<0·05);实验组移植肾HO-1蛋白含量分别为(297±61)及(468±51)ng/g,而对照组分别为(98±30)及(155±31)ng/g,两组相比差异具有统计学意义(t=8·27,14·83,P均<0·05)。与对照组相比实验组移植肾病理改变明显减轻(P<0·05),血肌酐水平明显降低(t=8·41,P<0·05)。结论腺病毒载体可成功介导HO-1基因对大鼠肾脏的转移,对自体移植肾缺血再灌注损伤具有保护作用。     

去细胞异体真皮、去细胞猪真皮和自体刃厚皮移植在临床中的应用

目的观察去细胞异体真皮或去细胞猪真皮加自体刃厚皮移植在深度烧伤和整形外科中的应用效果。方法采用去细胞异体真皮或我们研制的去细胞猪真皮加自体刃厚皮移植的方法,修复各种创面119例次,比较不同创面的植皮成活率,观察应用不同部位的皮肤覆盖去细胞异体真皮或去细胞猪真皮与植皮成活的关系,并对部分病例进行了组织学观察和随访。结果削痂、切痂和切瘢创面植皮成活率分别为(93．4％±3．1)％、(92．1±4．6)％和(94．5±3．8)％,三者间差异无显著意义;去细胞异体真皮加自体刃厚皮移植与去细胞猪真皮加自体刃厚皮移植,二者植皮成活率差异无显著意义。躯干、四肢自体刃厚皮覆盖的去细胞异体真皮或去细胞猪真皮,植皮成活率分别为(93．1±4．8)％、(89．0±6．2)％,而应用刃厚头皮或自体微粒皮加异体皮覆盖的去细胞异体真皮或去细胞猪真皮,植皮成活率明显下降(P<0．05或0．01)。组织学观察,术后19个月时表皮、真皮形态正常,胶原纤维排列规则,未见胶原纤维明显增生和瘢痕化,无皮肤附件。成活的复合移植皮肤,与邻近正常肤色近似,色素沉着轻,无明显皱缩,触之软,活动度好。结论去细胞异体真皮或去细胞猪真皮加自体刃厚皮移植修复深度烧伤创面或切瘢后创面不失为一种较理想的材料。     

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.     

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.     

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.     

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.