雌激素对β淀粉样蛋白(25~35)诱导大鼠皮质神经元细胞凋亡的影响

目的研究雌激素抑制β淀粉样蛋白(Aβ)诱导大鼠神经细胞凋亡的作用机制。方法通过乳酸脱氢酶(LDH)释放率的测定及膜联蛋白V/碘化丙啶双染色流式细胞术观察17β-雌二醇(17β-E2)对Aβ(25~35)诱导的大脑皮质神经元细胞死亡及凋亡的影响,用半定量逆转录-聚合酶链反应(RT-PCR)方法检测Bcl-2在转录水平的表达。结果Aβ(25~35)可以诱导大鼠皮质神经元细胞凋亡,下调抗凋亡分子Bcl-2的表达。17β-E2预处理48 h显著抑制Aβ(25~35)诱导的大鼠皮质神经元细胞凋亡,并且显著抑制Aβ(25~35)下调Bcl-2表达的作用。结论Aβ可以通过下调抗凋亡分子Bcl-2的表达诱导原代培养的大鼠皮质神经元细胞凋亡,雌激素可以通过上调抗凋亡分子Bcl-2的表达来抑制Aβ诱导的大鼠皮质神经元细胞凋亡。     

组织转谷氨酰胺酶特异性抑制剂预防肝纤维化的实验研究

目的 观察组织转谷氨酰胺酶(tTG)特异性抑制剂六甲烯胺对四氯化碳(CCl4)诱导的大鼠肝纤维化形成的影响.方法 雄性SD大鼠100只,按随机数字表法分成正常对照组(20只)、肝纤维化组(40只)、六甲烯胺组(40只).用腹腔内注射CCl4诱导大鼠肝纤维化模型,在注射CCl4的前2 d开始腹腔内注射六甲烯胺(112 mg·kg-1·d-1),直到注射CCl4的第4、8周处死大鼠,摘取肝脏并提取血清,应用RT-PCR检测tTG、α-平滑肌抗体(α-SMA)、Ⅰ型胶原蛋白和基质金属蛋白酶抑制剂-1(TIMP-1)等基因的mRNA表达情况,应用Western blot检测tTG和α-SMA蛋白的表达,肝功能和肝脏组织中羟脯氨酸的含量,同时取大鼠肝脏行组织学检查,并对肝纤维化程度进行半定量计分系统分级评分.采用单因素方差分析检测结果.结果 CCl4注射8周后,肝纤维化组肝损伤明显,ALT、总胆汁酸、Tbil、羟脯氨酸、tTG、α-SMA、Ⅰ型胶原蛋白酶、TIMP-1分别为(1313±157)U/L、(99.9±18.5)μmol/L、(10.9±1.6)μmol/L、(55±12)μg/g、145.6±51.2、130.3±44.6、211.3±75.1、162.4±53.5;而六甲烯胺处理后,肝纤维化程度、肝功能指标均显著降低,ALT、总胆汁酸、Tbil、羟脯氨酸、tTG、α-SMA、Ⅰ型胶原蛋白酶、TIMP-1分别为(378±87)U/L、(61.0±12.7) μmol/L、(9.8±1.7)μmol/L、(70±14)μg/g、48.6±12.3、40.7±12.3、63.9±16.0、59.2±23.4.结论 六甲烯胺能通过抑制tTG途径显著改善CCl4诱导的大鼠肝纤维化程度.     

二氮嗪对幼龄大鼠深低温脑缺血再灌注后氧自由基及细胞凋亡的影响

目的 探讨二氮嗪对幼龄大鼠深低温脑缺血再灌注后氧自由基和细胞凋亡的影响及相关的脑保护作用机制.方法 将54只3周龄健康sD大鼠随机分为假手术组、模型组和二氮嗪组,每组18只,建立深低温脑缺血再灌注模型.于术后24 h处死大鼠,检测脑组织超氧化物歧化酶(SOD)、丙二醛的含量,Western Blot法检测脑组织细胞质细胞色素C含量,免疫组化法检测脑组织细胞质Caspase-3含量.结果 模型组脑组织中SOD含量为(198±41)U/mg,低于假手术组的(321±36)U/rag(P<0.01);丙二醛含量为(212±21)nmol/mg,高于假手术组的(100±23)nmol/mg(P<0.01);细胞色素C蛋白表达(0.72±0.09)和Caspase-3蛋白表达(83±10)均高于假手术组(0.17±0.02和115±9)(P<0.01).二氮嗪组脑组织SOD含量为(264±34)U/rag,高于模型组(P<0.05);而丙二醛含量(174±19)nmol/mg、细胞色素C蛋白表达(0.41±0.05)和Caspase-3蛋白表达(99±11)均低于模型组(P<0.05).结论 二氮嗪对幼龄大鼠深低温脑缺血再灌注损伤具有脑保护作用,其机制与抑制氧自由基产生和细胞凋亡有关.     

诱导供者胰岛细胞高表达血红素加氧酶-1延长大鼠胰岛移植物的存活时间

目的 探讨钴原卟啉(CoPP)诱导大鼠胰岛细胞高表达血红素加氧酚1(HO-1)后,对延长胰岛移植物存活时间的作用.方法 (1)将分离和纯化的供者(BN大鼠)胰岛细胞分为CoPP诱导组和未诱导组.CoPP诱导组供者在分离胰岛细胞前3天和前1天腹腔注射2.5 mg/kg的CoPP,未诱导组不注射CoPP.诱导后,采用免疫荧光法及Western免疫印迹法检测两组胰岛细胞中HO-1的表达情况,采用酶联免疫吸附试验(ELISA)和葡萄糖刺激试验检测胰岛细胞的胰岛素释放水平.(2)Lewis大鼠经四氧嘧啶静脉注射后建立糖尿病模型,取10只成功建立糖尿病模型的大鼠作为胰岛细胞移植的受者,随机平均将受者分为实验组和对照组,分别移植经CoPP诱导和未经诱导的供者胰岛细胞.移植后,观察和比较两组受者胰岛移植物的存活时间和发生排斥反应后胰岛移植物的组织病理学变化.结果 CoPP诱导组胰岛细胞高表达HO-1,而未诱导组不表达HO-1;CoPP诱导组和未诱导组供者胰岛细胞胰岛素分泌量,在低糖刺激下分别为(15.65±0.89)mU/L和(12.28±0.89)mU/L(P>0.05),在高糖刺激下分别为(46.60±1.13)mU/L和(19.01±1.49)mU/L(P<0.05),刺激指数分别为2.98±0.10和1.55±0.01(P<0.05).实验组和对照组胰岛移植物平均存活时间分别为(12.20±5.67)d和(5.60±1.14)d(P<0.05);当受者发牛排斥反应时,对照组胰岛移植物周边可见明显的淋巴细胞、成纤维细胞以及单个核细胞浸润,而实验组细胞浸润的程度明显较轻.结论 CoPP可诱导大鼠胰岛细胞高表达HO-1,其对胰岛细胞有明显保护作用.移植高表达HO-1的胰岛细胞能显著延长胰岛移植物的存活时间.     

改进型左侧精索静脉曲张对大鼠睾丸酶及增殖细胞核抗原的影响

目的 观察改进型左侧精索静脉曲张(ELV)对大鼠睾丸酶及增殖细胞核抗原(PCNA)的影响.方法 利用改进的方法建立青春期SD大鼠左精索静脉曲张的模型21只;假手术组SD大鼠15只作对照组.术后3个月,取部分睾丸组织匀浆提取上清液,比色法定量检测乳酸脱氢酶(LDH)、琥珀酸脱氢酶(SDH)、葡萄糖-6-磷酸脱氢酶(G6PDH)活性,利用酶联免疫吸附试验(ELISA)测定PCNA的浓度.结果 实验组左睾丸内的LDH、G6PDH活性分别为(8.17±3.47)、(34.00±16.29)U/mg,与对照组同侧(11.98±2.26)、(54.88±20.87)U/mg比较下降,与实验组右睾丸(12.69±3.97)、(78.03±25.28)U/mg比较也下降,差异均有统计学意义(P<0.05);实验组左睾丸内的SDH活性(1.22±0.41)U/mg与对照组同侧(1.74±0.43)U/mg比较下降,差异有统计学意义(P<0.05),与实验组右睾丸(1.62±0.56)U/mg比较下降,差异无统计学意义(P>0.05);实验组左睾丸内PCNA(669.10±205.39)mU/ml与对照组同侧(776.81±231.72)mU/ml比较下降,和实验组右睾丸(800.81±172.02)mU/ml比较也下降.差异均无统计学意义(P>0.05).结论 改进型ELV致睾丸酶活性降底和PCNA的变化,这些变化可能是影响生育能力的因素之一.     

氯胺酮对SD幼鼠海马神经元细胞凋亡和NR2B蛋白的影响

目的观察氯胺酮对海马神经元细胞凋亡和N-甲基-D-天(门)冬氨酸受体2B亚基(NR2B)蛋白的影响。方法45只新生第7天SD大鼠随机均分为腹腔注射氯胺酮25 mg/kg组(K1组)、50 mg/kg组(K2组)和生理盐水50 ml/kg组(K0组)。24 h后每组取5只幼鼠处死,用TUNEL法检测海马神经元细胞凋亡,免疫组化法检测NR2B蛋白表达,剩余30只动物喂养至42 d,用Mor-ris水迷宫评价大鼠成年后的空间学习记忆能力。结果在腹腔注射24 h后,海马神经元细胞凋亡数明显增加(K1组9.5±4.2,K2组23.4±7.6,K0组5.3±1.7);NR2B蛋白免疫组化染色切片灰度值K1组为182.36±4.17,K2组为179.11±4.28,K0组为198.25±3.38;但是成年后在Morris水迷宫中的学习记忆能力并没有明显变化。结论单次注射氯胺酮24 h后,诱发新生第7天SD大鼠显著增强的海马神经元细胞凋亡,上调NR2B的表达,但对于成年后的空间学习记忆能力无明显影响。     

脂质胞壁酸诱导的延迟预适应对大鼠局灶性脑缺血/再灌注损伤的保护作用

目的　探讨脂质胞壁酸 (LTA)诱导的延迟预适应对大鼠局灶性脑缺血 /再灌注 (I/R)损伤的作用。方法　采用局灶性脑缺血 2h ,再灌注 12h或 2 4h的方法 ,预适应组大鼠缺血前 2 4h腹腔注射LTA 1mg/kg) ,检测脑组织再灌注 2 4h后组织含水量、超氧化物歧化酶 (SOD)和丙二醛(MDA) ,再灌注 12h后大鼠神经症状、组织中一氧化氮 (NO)的含量 ,同时用TUNEL染色法检测神经细胞的凋亡。结果　I/R组脑组织中SOD和MDA的含量分别为 (2 .72± 0 .3 8)kU /g蛋白和(1.83± 0 .3 3 ) μmol/g蛋白 ,LTA预适应组SOD活性和MDA的含量分别为(3 .68± 0 .40 )kU /g .蛋白和 (1.2 7± 0 .2 1) μmol/g蛋白 ,与I/R组比较差异有统计学意义 (P均 <0 .0 1) ;I/R组NO含量和凋亡百分率为 (3 4.4± 6.3 ) %、(0 .85 2± 0 .0 90 ) μmol/g蛋白 ,而LTA预适应组神经细胞的凋亡百分率和脑组织中NO含量为 (7.2± 3 .2 ) %、(0 .5 94± 0 .0 78) μmol/g .蛋白均较I/R有显著降低 (P均 <0 .0 1)。结论　LTA诱导的延迟预适应能显著减少大鼠脑组织再灌注损伤 ,减少组织坏死和细胞凋亡。其作用机制与减少脑I/R后自由基和NO毒性作用有关。     

半胱氨酸酶-3在依托利酸诱导肝癌细胞凋亡中的作用

目的　探讨选择性环氧合酶 (COX)抑制剂依托利酸 (etodolac)诱导肝癌SMMC772 1细胞凋亡的分子机制。方法　采用流式细胞术、DNA琼脂糖凝胶电泳法测定细胞凋亡情况 ;West ernblotting法检测不同浓度etodolac处理后凋亡相关蛋白Bcl 2、Bax表达的变化 ;并以流式细胞术检测半胱氨酸酶 3 (Caspase 3 )酶活性的变化。 结果　流式细胞术显示etodolac(0、0 .2 5、0 .5 0、1.0 0、2 .0 0mmol/L)作用SMMC772 1细胞 48h后 ,对照处理组 (0mmol/L)没有出现凋亡峰 ,其余各组(0 .2 5、0 .5 0、1.0 0、2 .0 0mmol/L)出现明显的凋亡峰 ,其凋亡率分别为 (16.3± 3 .1) %、(19.9±3 .6) %、(2 2 .9± 3 .2 ) %、(3 1.2± 3 .3 ) % (P <0 .0 0 1) ;DNA琼脂糖凝胶电泳出现明显的DNALad der ;不同浓度etodolac处理后凋亡相关蛋白Bcl 2表达下降 ,Bax表达增加 ;随着etodolac处理浓度的增加 ,表达活性Caspase 3的细胞百分率分别为 (3 .61± 0 .3 2 ) %、(2 .93± 0 .15 ) %、(10 .2 9±0 .3 9) %、(2 7.3 3± 1.2 8) %、(5 7.40± 1.69) % (P <0 .0 0 1)。结论　选择性COX 2抑制剂可能通过调节Bcl 2、Bax蛋白表达活化Caspase 3 ,从而诱导肝癌SMMC772 1细胞凋亡。     

红景天苷对低氧诱导大鼠海绵体平滑肌细胞凋亡的抑制作用

目的:探讨红景天苷对低氧诱导的大鼠海绵体平滑肌细胞(CCSMCs)凋亡的影响。方法:采用酶消化法体外培养大鼠CCSMCs,抗α-平滑肌肌动蛋白(α-SMA)和结蛋白(Desmin)免疫荧光鉴定CCSMCs纯度;通过MTT法筛选红景天苷无毒剂量;以低氧混合气体(1%O2,5%CO2,94%N2)通入缺氧小室建立细胞低氧模型;细胞分为3组:正常组,低氧组,红景天苷(32μg/ml)干预组,采用流式细胞术观察各组CCSMCs凋亡的情况,Western印迹检测caspase-3蛋白表达水平。结果:成功培养大鼠CCSMCs,免疫荧光显示绝大部分细胞α-SMA、Desmin阳性;≤32μg/ml的红景天苷对细胞无明显的毒性;低氧组CCSMCs早期凋亡[(18.69±1.29)%]较正常组[(12.77±1.41)%]明显增多(P0.01),低氧组晚期凋亡[(21.03±1.53)%]较正常组[(14.63±2.00)%]亦增加(P0.05),同时,活化型caspase-3蛋白表达上升(P0.01);32μg/ml红景天苷剂量下可有效降低低氧诱导的CCSMCs早期凋亡率[(13.46 1.87)%](P0.01),活化型caspase-3蛋白表达下降(P0.01)。结论:红景天苷能够降低低氧诱导的CCSMCs活化型caspase-3蛋白的表达,抑制了低氧诱导的CCSMCs凋亡。     

藤梨根对人脑胶质瘤U251细胞的影响及其机制

目的 探讨藤梨根对人脑胶质瘤U251细胞的作用及其机制.方法 常规培养人脑胶质瘤细胞株U251,分别加入不同浓度(50、100、200 mg/L)藤梨根作用48 h后细胞计数试剂盒(CCK-8)法检测U251的细胞活性;取50 mg/L藤梨根作用48 h后的细胞,反转录-聚合酶链反应(RT-PCR)法检测信号转导和转录活化因子3(STAT3) mRNA的表达,Western blot检测STAT3蛋白的表达.结果 藤梨根作用48 h后U251细胞凋亡率明显增加,不同浓度的凋亡率分别为50 mg/L:(26.51士1.30)％、100 mg/L:(55.92 ±2.40)％、200mg/L:(63.69±2.70)％;50 mg/L藤梨根处理后的U251细胞中STAT3 mRNA和蛋白表达水平均下调,检测其中相关蛋白表达结果显示,藤梨根处理组中磷酸化STAT3(p-STAT3)和B淋巴细胞瘤/白血病-2(bcl-2)的表达下调,而bcl-2相关X蛋白(bax)的表达上调.结论 藤梨根可以抑制脑胶质瘤细胞的增殖,其机制可能与藤梨根调控STAT3信号通路有关.     

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 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.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

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.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.     

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.     

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.     

The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans

Background : Ketamine in sub-dissociative doses has been shown to have analgesic and phantom-Limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood.
Methods : Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS).
Results : Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all patients at the highest dose (0.45 mg/ kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. The remaining 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/ kg ketamine doses than for morphine 10 mg.
Conclusion : We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.