CCl4慢性肝损致无白蛋白受体鼠对移植骨髓细胞肝细胞增殖的影响

目的 观察和研究F344来源的骨髓细胞(bone marrow cells,BMCs)能否驻存于γ-全身照射的先天性无白蛋白大鼠的骨髓,进而转化为产白蛋白肝细胞,移植后给予四氯化碳(carbon tetracholoride,CCl4)后对这些细胞增殖的影响.方法 雄性F344大鼠为供体,而雄性F344alb(先天性无白蛋白大鼠)为受体,分为4组:组Ⅰ(n=10)为正常对照组,不接受肝损处理,无全身射线照射和阴茎静脉骨髓细胞移植;组Ⅱ(n=10)为肝损无移植组,只接受肝损处理,无全身射线照射和阴茎静脉骨髓细胞移植;组Ⅲ(n=1O)为正常移植组,全身射线照射后阴茎静脉移植骨髓细胞1×107;组Ⅳ(n=10)为肝损移植组,接受CCl4注射肝损,全身射线照射后阴茎静脉骨髓细胞移植1×107BMCs,其中,γ-照射剂量为7.5 Gy,F344大鼠的BMCs经受体的阴茎静脉注入.移植后四周,CCl4腹腔内注射铸成大鼠慢性肝损模型,细胞移植12周后,处死大鼠.肝脏切片用抗白蛋白抗体行白蛋白免疫染色,检测从受体骨髓细胞和肝脏切片中呈多于6个白蛋白阳性簇状分布的肝细胞群中提取的DNA和血清中白蛋白的水平.结果 ①尽管组Ⅰ肝脏切片可发现少量散在的1个或2个白蛋白阳性肝细胞,但是白蛋白阳性肝细胞呈多于6个的簇状分布仅发现于γ-射线全身照射后接受BMCs移植的肝切片中(组Ⅲ和组Ⅳ),而且组Ⅳ中呈多于6个的簇状分布的肝细胞数明显多于组Ⅲ,有统计学意义.②从F344alb受体(组Ⅲ和组Ⅳ)骨髓细胞及肝脏切片中微切的呈多于6个白蛋白阳性簇状分布的肝细胞群中提取的DNA中可检测到正常的白蛋白基因序列.③组Ⅳ较组Ⅲ血清中白蛋白水平显著升高.结论 ①F344来源的骨髓细胞移植入全身射线照射的F344alb受体,可驻存于F344alb受体的骨髓内,进而转化为产白蛋白的肝细胞.②F344来源的骨髓细胞移植入全身射线照射的F344alb受体,4周后CCh腹腔内注射铸成大鼠慢性肝损模型可明显增加骨髓细胞的增殖.③全身射线照射后移植F344供体骨髓细胞,之后CCl4腹腔内注射铸成大鼠慢性肝损模型的F344alb受体的外周血中白蛋白水平可明显提高.     

骨髓细胞移植改善宿主肝细胞功能研究

目的 观察骨髓问充质细胞(BMCs)移植能否提高严重肝功能损害合并再生障碍的同种先天性无白蛋白大鼠(F344alb)肝再生和修复能力.方法 F344大鼠为供体,F344alb受体鼠接受Retrorsine(RS)1次/2周腹腔注射2次后4周行2/3肝切除(PH).正常F344alb为组Ⅰ(n=5);BMCs移植为组Ⅱ(n=8);RS/PH预处理为组Ⅲ(n=8);RS/PH预处理后BMCs移植为组Ⅳ(n=8);RS/PH预处理后肝实质细胞移植为组V(n=8).4周后行各组大鼠肝脏形态学和组化染色研究,检测肝功能,及肝组织和骨髓基因检测.结果 (1)生存率:组Ⅳ75%,组Ⅴ 50%,组Ⅲ37.5%,组Ⅰ和组Ⅱ 100%.(2)4周后组肝再生率(67.38±8.66)%显著高于组Ⅳ、Ⅲ[(55.31±8.69)%,(44.27±6.51)%].(3)PH后1 d,组Ⅲ、Ⅳ、V血清TB、ALT显著升高;PH后2 d,组Ⅳ血清,rB、ALT显著下降.(4)组Ⅳ、Ⅴ肝组织切片白蛋白免疫组织化学染色显示白蛋白染色阳性肝细胞呈簇状分布.(5)F344来源白蛋白基因片段出现在组Ⅳ、Ⅴ大鼠肝组织内.(6)PH后2、4周,组Ⅳ、Ⅴ血清白蛋白显著升高.结论 BMCs移植可提高严重肝损合并再生障碍受体鼠肝再生能力,保护肝功能,促进肝修复.     

载肝细胞生长因子的纳米粒子治疗急性肝衰竭大鼠

目的 观察载肝细胞生长因子(HGF)的聚乳酸-O-羧甲基壳聚糖(PLA-O-CMC)纳米粒子培养的大鼠肝细胞腹腔内移植对急性肝衰竭(ALF)大鼠的治疗效果.方法 分别将5 ml培养24 h的大鼠肝细胞(5.0×107个)(Ⅰ组)、PLA-O-CMC纳米粒子培养的大鼠肝细胞(Ⅱ组)、载HGF的PLA-O-CMC纳米粒子培养的大鼠肝细胞(Ⅲ组)移植到ALF大鼠腹腔内,以PLA-O-CMC纳米粒子培养的大鼠肝细胞腹腔移植加每天静脉注射HGF 10 μg/kg×7 d(Ⅳ组)和5 ml RPMI 1640培养基腹腔内注射(Ⅴ组)作为对照.观察受体大鼠存活率、肝功能、肝组织光镜和电镜变化.结果 移植后14d大鼠的存活率Ⅰ～Ⅴ组分别为50.00％、68.75％、81.25％、75.00％和18.75％,各移植组高于对照组,Ⅲ组最高.移植后24 h,Ⅱ～Ⅳ组各项肝功能指标开始好转,至移植后7d,各组间除谷丙转氨酶(ALT)外,差异无统计学意义(P＞0.05).Ⅲ组的肝功能和肝脏病理损害恢复最快,其次为Ⅳ、Ⅱ、Ⅰ组,Ⅴ组恢复最慢、最差.结论 应用载HGF的PLA-O-CMC纳米粒子培养的大鼠肝细胞腹腔内移植治疗ALF大鼠能逆转肝功能,提高生存率,较静脉途径给予HGF的治疗效果更好.     

共微囊化异种肝细胞胰岛联合移植治疗急性肝衰

目的　探讨共微囊化异种肝细胞胰岛联合移植对急性肝衰的治疗作用。方法　D 氨基半乳糖诱导小鼠急性肝衰 ;Seglen法分离大鼠肝细胞 ;Sutton法分离胰岛 ;自制双喷头成囊器制备微囊。比较生理盐水、自由肝细胞移植、微囊化肝细胞移植、共微囊化肝细胞胰岛联合移植 4组间存活率、体重、谷丙转氨酶、血清白蛋白、总胆红素、血糖等指标的变化情况。结果　共微囊化肝细胞胰岛联合移植组存活率达 10 0 % ,组间差异有显著性 (P <0 .0 5 ) ,各项生化指标也明显占优。肝细胞与胰岛 β细胞可在微囊内融合。 结论　共微囊化肝细胞胰岛联合移植对氨基半乳糖诱导的急性肝衰有最佳的治疗作用     

近交系大鼠小肠移植模型排斥反应的动态观察

目的:动态观察近交系大鼠小肠移植排斥反应发生规律,探讨该模型对小肠移植排斥反应研究的价值.方法:选用近交系大鼠F344(RT11)和BN(RT1n),根据改良Monchik法建立下腔静脉回流式异位全小肠移植模型.实验分为同系移植组(F344→F344,ITx组)和同种移植组(BN→F344,ATx组),每组各制作实验模型8只.结果:①ITx组大鼠平均生存期30d以上,ATx组大鼠平均存活12d.②ITx组大鼠术后各时点的大体观察无明显差异,而移植小肠病理组织学POD 3d呈非特异性炎症反应表现,POD 0、5、7、9d 与正常小肠的组织学特征基本相同.③IL-2Rα和γ-INF mRNA转录水平显著性改变早于排斥反应的病理诊断.④ATx组在POD 5、7、9d的大体表现与组织病理改变分别符合轻、中、重度排斥反应的诊断标准.结论:近交系大鼠BN→F344与近交系大鼠F344→Wistar适用于小肠移植排斥反应实验研究.     

急性肝衰竭大鼠载肝细胞生长因子纳米粒子肝细胞移植后有丝分裂指数和Ki-67表达变化及意义

目的 探讨急性肝衰竭(ALF)大鼠载肝细胞生长因子(HGF)的聚乳酸-氧-羧甲基壳聚糖(PLA-O-CMC)纳米粒子肝细胞移植后有丝分裂指数和Ki-67抗原的表达变化及意义.方法 D-氨基半乳糖腹腔内注射制作大鼠ALF模型,48 h后分别将Ⅰ型胶原(Ⅰ组)、PLA-O-CMC纳米粒子(Ⅱ、Ⅳ组)、载HGF的PLA-O-CMC纳米粒子(Ⅲ组)培养的大鼠肝细胞(均为5×107个,5 ml)移植到ALF大鼠腹腔内.以每日静脉注射HGF 10μg/kg×7 d(Ⅳ组)、5 Ml RPMI 1640腹腔内注射(Ⅴ组)作为对照.观察其14 d存活率、血清及肝组织HGF浓度、肝组织病理及有丝分裂指数(MI)、Ki-67变化.结果移植后14 d Ⅰ～Ⅴ组ALF大鼠的存活率分别为50.00％、68.75％、81.25％、75.00％、18.75％.各纳米移植组高于V组.Ⅲ组3 d时肝组织HGF浓度最高,平均为5882.91 μG／L.Ⅲ组肝组织结构恢复更快,5 d时平均MI 10.20％0、7 d时平均MI 10.20‰、7 d时Ki-67平均标记指数16.8‰,均高于Ⅴ组.结论 应用载HGF的PLA-O-CMC纳米粒子培养的大鼠肝细胞腹腔内移植治疗ALF大鼠能促进肝再生相关抗原表达.

Abstract：

Objective To evaluate the change and significance of Ki-67 antigen expression follow ing hepatocyte transplantation using hepatocyte growth factor (HGF) loaded polylactic acid-O-carboxymethylchitosan (PLA-O-CMC) nanoparticles in rats with acute liver failure (ALF). Methods ALF models of rats were established by D-galactosamine intraperitoneal injection. Rat hepatocytes type Ⅰ collagen suspension (group Ⅰ ),rat hepatocytes co-cultured with PLA-O-CMC nanoparticles ( groups Ⅱ ,Ⅳ ) and rat hepatocytes co-cultured with HGF loaded PLA-O-CMC nanoparticles ( group Ⅱ ) (5 × 107 cells each group,5 ml) were transplanted into the abdominal cavity of SD rats at 48 h after D-Gal injection. Intravenous injection of HGF ( 10 μg/kg for 7 days) ( group Ⅳ ) and RPMI 1640 injection (group Ⅴ ) were used as the negative groups. The 14th-day survival rate of rats,pathological change and mitotic index of liver,Ki-67 antigen labeling index of ALF rat livers were observed. Results The 14th-day survival rate in groups Ⅰ -Ⅴ was 50.00％,68. 75％,81.25％,75.00％,18.75％,and that in nano-transplanted groups was higher than in group Ⅴ. At the 3rd day,the concentration of HGF in liver tissue of group Ⅲ,average 5882. 91 μg/L was the highest. The hepatic lobules structure in group Ⅲ recovered faster. The average mitotic index in group Ⅱ at the 5th day was 10. 20‰ and the average Ki-67 labeling index at the 7th day was 16. 8‰,which were all higher than in group Ⅴ. Conclusion Intraperitoneal transplantation of HGF loaded PLA-O-CMC nanoparticle-attached hepatocytes for treatment of ALF can promote the liver regenerationassociated antigen expression.     

小鼠原位脂肪肝移植模型的建立

目的　建立了ob/ob小鼠脂肪肝移植模型 ,探讨保证建模成功的关键因素。方法　采用小鼠非动脉化肝移植技术 ,5～ 7周肥胖小鼠为供体 ,正常小鼠为受体 ,双袖套法行原位肝移植。受体肝组织行HE染色和油红O染色 ,血清ALT、AST水平检测采用常规生化分析法。结果非脂肪肝移植组 (lean to lean)受体长期存活率 (n =10 )为 70 % ,脂肪肝移植组 (ob/obtoagematchedlean)受体存活率为 0 (n =10 ) ,差异有显著性 (P <0 .0 5 )。脂肪肝移植给体积相当的正常小鼠 ,其短期存活率为 3 0 % (n =10 ) ,所有小鼠术后存活并苏醒 ,但均未超过 2 4h。脂肪肝移植受体ALT水平为 (62 85± 2 93 7)U /L ,AST为 (5 812± 2 942 )U /L ;而正常小鼠移植组ALT与AST水平分别为 (5 96± 114 )U /L ,(1796± 870 )U/L ,差异有显著性 (P <0 .0 5 ) ,组织学检测显示大量胆管中央凝固性坏死伴出血。结论　该模型的成功建立为我们提供了一种新的肝原发性肝无功能移植模型 ,为脂肪肝移植后脂肪肝细胞受损的机制研究奠定了基础。     

双层法氧合冷保存心跳停搏大鼠肝细胞移植研究

目的 观察双层法(TLM)氧合冷保存较UW保存能否改善心跳停搏供体(NHBD)肝细胞存活率和功能.方法 SD大鼠为供体,建立NHBD模型,NAPs大鼠为受体.根据热缺血时间(WIT)15 m/n和30 m/n分成2组;按TLM、UW分别保存3、12 h和未保存再各分5个亚组(n=5).检测NHBD肝细胞存活率和ATP水平,观察肝细胞移植(HTx)后肝细胞形态和功能.结果 TLM3、12 h组肝细胞存活率分别显著高于UW 3、12 h组[(69.7±4.1)%和(69.1±2.0)%比(55.1±2.3)%和(53.3±2.0)%;P<0.01];TLM 3、12 h组AlP水平分别显著高于UW 3、12 h组(3.25±0.79和3.06±0.67比2.25±0.53和1.63±0.40;P<0.05或P<0.01).HTx后几乎所有时间点TLM组血清白蛋白(ALB)水平都显著高于UW组(P<0.05或P<0.01).在HTx 14d后,形态学显示TLM组肝细胞保持强活力,糖原和ALB染色呈强阳性.结论 TLM氧合冷保存可显著改善和逆转NHBD肝细胞存活率和功能,减少NHBD肝细胞缺血性损伤.     

异种肝细胞移植治疗大鼠药物性肝衰的疗效观察

目的　观察异种肝细胞移植治疗大鼠药物性肝衰的疗效。方法　杂种豚鼠为供体 ,胶原酶消化法制备肝细胞。SD大鼠为受体 ,氨基半乳糖 (D GI)腹腔内 1次注射制作肝衰模型。 4 8h后将豚鼠肝细胞(1.5× 10 7个 )移植于大鼠脾内。同种移植及生理盐水为对照。移植后观察受体 2周存活率 ,在移植不同时间作移植物病理及组织化学检查。结果　受体 2周存活率 :异种移植组为 71% ,同种组为69 % (P >0 .0 5 ) ,生理盐水对照组为 2 5 % (P>0 .0 1)。豚鼠肝细胞移植后 12～ 2 4h其结构和功能基本保存完好。结论　与同种移植一样 ,异种肝细胞移植能逆转大鼠药物性肝衰。     

附加门体分流术对小体积移植肝保护作用的实验研究

目的 研究附加门体分流术对小体积移植肝的保护效果.方法 建立巴马小型猪小体积肝移植模型,将15只小型猪平均分为3组:(1)A组,小体积肝移植组(对照组);(2)B组,远端脾肾分流术+小体积肝移植组;(3)C组,肠腔H形分流术+小体积肝移植组.手术后观察动物7 d存活率,动态监测肝功能生化指标、自由门静脉压、门静脉血流量(PBF)以及移植肝组织病理学改变.结果 动物7 d存活率分别为:A组1/5,B组3/5,C组5/5.A组动物移植肝复流后自由门静脉压立即升高,高峰达(28.6±2.07)mm Hg(1 mm Hg=0.133 kPa),复流1 h后单位肝组织PBF达(3.56±0.1 1)ml·min-1·g-1;移植肝组织病理学改变严重,包括肝细胞气球样变或肝细胞坏死、肝窦淤血、肝实质出血.B、c组中动物肝功能酶学指标有所改善.移植肝复流后自由门静脉压显著低于A组水平(P<0.05),PBF保持相对平稳.移植肝组织病理学病变明显减轻.结论 附加门体分流术可能可以避免小体积移植肝的损伤.     

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.