外源性Tuftsin及其抑制物在急性胰腺炎中作用的实验研究

目的　探讨tuftsin及其抑制物在急性胰腺炎 (acutepancreatitis,AP)病情发展过程中的作用。方法　SD大鼠分为 5组 ,每组 2 4只 ,分为对照组、单纯tuftsin组、AP组、AP +tuftsin组、AP +tuftsin抑制物组。胰胆管逆行注射 4%牛磺胆酸钠建立AP模型 ,tuftsin及其抑制物组 ,自制模 2 0min后从股静脉注入tuftsin或其抑制物 75 μg kg。随机于 0、3、6、1 2h分批处死 ,留取胰腺 (体部 )组织甲醛固定 ,HE染色光镜观察胰腺病理改变程度并进行病理学评分。结果　对照组与单纯tuftsin组在不同时段病理学评分差异均无显著性 (P >0 .0 5 ) ;制模后 0h各组胰腺病理学评分差异无显著性 ,制模后 3、6、1 2h各组胰腺病理学评分均比对照组和单纯tuftsin组明显升高 ;AP +tuftsin组各时间段均较单纯AP组病理改变明显加重 ,差异有显著性 (P <0 .0 1 ) ;AP +tuftsin抑制物组在制模后 6、1 2h明显减轻胰腺病理改变程度 ,与单纯AP组比较差异有显著性 ,在制模后 3h对病变程度无明显影响。结论　在胰腺炎病情发展过程中tuftsin加重胰腺病理改变 ,应用tuftsin抑制物可减轻胰腺病变程度 ,阻止急性胰腺炎病情发展     

脾脏在急性胰腺炎中作用的实验研究

目的探讨脾脏在急性胰腺炎(AP)病情发展过程中的作用。方法SD大鼠分为5组每组24只，分别为对照组、脾切组、AP组、脾切 AP组、脾切 AP tuflsin组。胰胆管逆行注射4％牛磺胆酸钠建立AP模型，tuftsin组自制模20min后从股静脉注入tuftsin 75μg／kg。按随机原则在制模后0、3、6、12h分批处死，留取胰腺(体部)组织HE染色光镜观察胰腺病理改变程度进行病理学评分。结果制模后0、3、6、12h各组胰腺病理学评分均比对照组和单纯脾切组明显升高；AP组和脾切 AP tuftsin组制模后随时间的延长胰腺病理改变程度逐渐加重；脾切 AP组在制模后6h内胰腺病变程度逐渐加重，在制模后12h与6h比较胰腺病理学评分无显著性差异；与AP组比较，脾切 AP组在制模后3、6h对胰腺病理改变无影响，在制模后12h明显减轻胰腺病理改变；脾切 AP tuftsin组在制模后3、6h对胰腺病理改变程度无明显影响，在制模后12h胰腺病理改变明显加重，与AP组比较差异有显著性；脾切 AP tuftsin组与脾切 AP组相比在制模后3h无差异，在制模后6、12h胰腺病变程度明显加重。结论脾脏在急性胰腺炎病情发展过程中有一定的影响，表现为脾切除可减轻或阻止急性胰腺炎病情发展，外源性tuftsin可加重急性胰腺炎胰腺病理改变。     

早期应用维生素E对急性胰腺炎大鼠胰腺细胞凋亡和胰腺组织病变的影响

目的:探讨早期应用维生素E(Vit.E)对急性胰腺炎(AP)大鼠胰腺细胞凋亡和胰腺组织病变的影响.方法:将SD大鼠72只随机分为对照组、AP组和Vit.E治疗组,每组24只.经十二指肠行胆胰管逆行加压注射4%的牛磺胆酸钠,诱导大鼠AP模型.于术后3 h、6 h、12 h和24 h采取断颈方法分批处死动物,应用末端脱氧核苷酸转换酶(TdT)介导的原位末端标记(TUNEL)法检测胰腺细胞凋亡情况,观察各组胰腺组织的病理切片并进行组织病理学评分.结果:AP组和Vit.E治疗组术后胰腺凋亡细胞明显增多,两组在3 h和6 h的凋亡指数均无明显差异(P>0.05),而Vit.E治疗组在12 h和24 h的凋亡指数显著高于对应时相的AP组(12 h,P<0.05;24 h,P<0.01);与AP组比较,Vit.E治疗组胰腺组织病变较轻,12 h和24 h的胰腺组织病理学评分明显低于AP组(12 h,P<0.05;24 h,P<0.01).结论:早期应用抗氧化剂Vit.E能够有效地减轻AP胰腺病变的严重程度,而胰腺细胞凋亡可能是介导此过程的一个重要病理、生理改变.     

不同剂量坎地沙坦治疗大鼠急性胰腺炎的实验研究

目的：探讨选择性血管紧张素Ⅱ受体亚型AT1拮抗剂坎地沙坦不同剂量对大鼠急性胰腺炎（AP）的影响。方法：72只雄性SD大鼠随机分为正常对照组、AP组、AP＋低剂量坎地沙坦组（2 mg/kg）、AP＋高剂量坎地沙坦组（10 mg/kg）。腹腔注射20%L-精氨酸溶液建立AP动物模型;坎地沙坦用大鼠灌胃针灌注。各组大鼠分别在造模后12 h、24 h、48 h分批次等数量（6只/组/批）心脏取血处死。取胰腺组织观察胰腺病理变化并评分（按Rongione标准）,胰腺/体质量比,检测大鼠血清脂肪酶、TNF-α、IL-10的变化。结果：AP组胰腺炎症评分,胰腺/体质量比,血清脂肪酶、TNF-αI、L-10较对照组明显升高（P〈0.01）。其中胰腺/体质量比于造模后12 h已有明显升高,于48 h达到高峰;而血清脂肪酶和胰腺TNF-αI、L-10于造模后12 h达到高峰,此后有所下降,但仍然保持较高水平。坎地沙坦干预的实验组胰腺炎症评分,胰腺/体质量比,血清脂肪酶、TNF-α以及胰腺TNF-α较AP组降低（P〈0.05）,但低剂量坎地沙坦组与高剂量组间无显著差异（P〉0.05）。本实验中,应用坎地沙坦对AP大鼠血清及胰腺IL-10均无显著影响（P〉0.05）。结论：应用AT1受体拮抗剂坎地沙坦可以明显减轻L-精氨酸诱导大鼠急性胰腺炎的炎症及损伤。     

急性胰腺炎外周循环和胰腺微循环血小板内皮细胞粘附分子-1的表达

目的　探讨急性胰腺炎 (AP)外周循环和胰腺微循环中血小板内皮细胞粘附分子 1(PECAM 1)表达的变化规律。方法　Wistar大鼠 48只 ,诱发AP动物模型 ,用流式细胞仪分析脾静脉和下腔静脉血中多形核白细胞 (PMN )PECAM 1的表达。结果　 ( 1)在急性水肿性胰腺炎(AEP)动物模型中 ,外周循环和胰腺微循环PMNPECAM 1的表达水平在AEP 2、4h组相近 ,自 4h开始 ,外周循环PMNPECAM 1的表达上调直至 8h ;胰腺微循环PMNPECAM 1的表达下调直至 8h ,在AEP 8h组 ,差异有显著性 ( P <0 .0 5 )。 ( 2 )在急性坏死性胰腺炎 (ANP)模型中 ,胰腺微循环PMNPECAM 1的表达下调 ;外周循环组PMNPECAM 1的表达未见明显变化 ,在ANP 4、6h组 ,差异有显著性 (P <0 .0 5 )。结论　AEP胰腺微循环和外周循环PMNPECAM 1的表达呈逆向性 ,在胰腺微循环呈下调趋势 ,在外周循环呈上调趋势 ;ANP胰腺微循环PMNPECAM 1的表达呈加速性下调 ,该结果显示 ,在ANP早期 ,抑制PMNPECAM 1的过度表达可能有助于改善AP病理改变。     

水肿型胰腺炎向坏死型胰腺炎进展中VEGF的表达及意义

目的：探讨在胰腺微循环障碍加重过程中血管内皮生长因子（VEGF）的表达及意义。方法：将大鼠随机分为假手术对照组（N组）、急性水肿型胰腺炎组（AEP组）及急性坏死型胰腺炎组（ANP组）。于建模后6、12和24h,分别采用ELISA法检测各组血清中的VEGF、TNF-α及淀粉酶（AMY）含量,免疫组织化学方法检测各组胰腺组织中VEGF蛋白的表达情况,并分析比较。结果：AEP组与ANP组胰腺组织中各时相点VEGF染色评分均明显高于N组（P〈0．05）;建模6hANP组的评分显著高于AEP组（P〈0．05）,而12和24hANP组的评分均明显低于AEP组（P〈0．05）。ANP组和AEP组血清VEGF、TNF-α与AMY含量均显著高于N组（P〈O05）;ANP组与AEP组之间差异亦有统计学意义（P〈0．05）,但AEP组建模24hVEGF含量和12hAMY含量与ANP组差异无统计学意义（P〉0．05）;血清VEGF与TNF-α（正相关（P〈O.05）。结论：VEGF作为相对独立的微循环影响因素与全身炎症反应呈正相关,但在胰腺微循环障碍持续加重期,胰腺组织及血管内皮细胞严重受损,VEGF表达减少,胰腺坏死病变难以逆转。     

甘遂对重症急性胰腺炎大鼠胰腺组织微循环的影响及其机制

目的： 探讨甘遂对重症急性胰腺炎（SAP）大鼠胰腺组织微循环的影响及其机制。方法：SD大鼠随机分为假手术组（S组）、SAP组和甘遂治疗组（K组），每组40只。检测各组手术后2，6，12，24h的血清淀粉酶水平，胰腺组织TXB2和6-Keto-PGF1α含量、COX-2mRNA和蛋白表达水平、光镜和电镜观察胰腺组织结构，以及术后72h死亡率。结果：（1）胰腺组织TXB2，6-Keto-PGF1α水平及TXB2/PGF1α比值：SAP组在各时间点均较S组显著升高（P<0.01）；K组TXB2及TXB2/PGF1α比值在6，12，24h点均较SAP组显著降低（P<0.01），但仍高于S组（P<0.01）。(2)COX-2mRNA和蛋白表达：S组COX-2mRNA和COX-2蛋白表达均极弱；SAP组表达均明显；K组COX-2mRNA表达6，12h明显弱于SAP组（P<0.05），COX-2蛋白表达6，12，24h均显著低于SAP组（P<0.01）。(3)胰腺组织TXB2/PGF1α比值与COX-2蛋白表达呈显著正相关（r=0.867,P<0.01）。(4)光镜和电镜观察：S组胰腺组织结构正常；SAP组胰腺组织有出血坏死，微血管内大量血栓形成；K组胰腺组织损害较SAP组减轻，微血管内血栓明显减少。（5）72h死亡率：S组为0%，K组为12.5%，两者均明显低于SAP组（62.5%）（均P<0.05）。结论：重症急性胰腺炎时有COX-2 的高表达和TXA2/PGI2之间的失衡，甘遂可以下调COX-2的表达，纠正TXA2/PGI2之间的失衡，而改善胰腺微循环。这可能是其治疗大鼠SAP的作用机理之一。     

冷缺血时间对大鼠胰岛结构和功能的影响

目的 探讨胰腺的冷保存时间对胰岛的获得量、活性、纯度及功能的影响.方法 采用Wistar大鼠,切取其胰腺,然后保存于4℃UW液中,分别于保存3 h(3 h组)、6 h(6 h组)、9h(9 h组)、12 h(12 h组)、15 h(15 h组)、18 h(18 h组)和21 h(21 h组)取出胰腺,采用明尼苏达大学改良方法分离、纯化胰岛,并设不经过冷保存的对照组.分离、纯化所得的胰岛以双硫腙染色,分析胰岛数量与纯度;丫啶橙/溴化乙啶染色分析胰岛活性;测定胰岛在葡萄糖刺激下的胰岛素分泌量.结果 对照组每个大鼠胰腺平均叮获得560当量胰岛,形态完整.纯度达到88%,活性达到94%.3 h组和6 h组的胰岛获得量略有下降,但与对照组相比,差异无统计学意义.9 h组、12 h组、15 h组、18 h组和21 h组的胰岛获得量较对照组、3 h组和6 h组明显下降(P＜0.01,P＜0.05),各组间相比较,差异也有统计学意义(P＜0.01),且随保存时间的延长,各组的胰岛活性和纯度也逐渐下降.9 h组、12 h组和15 h组胰岛细胞形态基本完整,但可见少数细胞被膜不完整,内分泌颗粒外溢.18 h组和21 h组胰岛形态不规则,被膜破裂,大量内分泌颗粒外溢.对照组、3 h组和6 h组对高糖刺激反应良好,三者问的胰岛素释放指数(SI)的差异无统计学意义,保存9 h以后,各组SI均较对照组、3 h组和6 h组明显下降(P＜0.01,P＜0.05),且各组间的差异也有统计学意义(P＜0.01),18 h组和21 h组尤其明显.结论 采用UW液低温保存大鼠胰腺6 h以内,获得的胰岛的数量较多,质量较好;保存6～15 h,获得的胰岛数量及质量有所下降,但仍然可以用于移植;保存时间超过15 h,获得的胰岛数量及质量明显下降,不宜用于移植.     

磷脂酰肌醇3-激酶γ基因敲除对急性胰腺炎小鼠腺泡细胞的影响

目的:探讨磷脂酰肌醇3-激酶γ(PI3Kγ)基因敲除对急性胰腺炎(AP)小鼠病变程度、腺泡细胞功能以及对HSP70表达的影响。方法:雄性野生型(WT)C57BL/6小鼠和雄性PI3Kγ基因敲除(KO)小鼠各12只,随机均分为对照组和AP组,采用腹腔内注射蛙皮素诱导在体AP模型,对照组以同样的方式和体积给予生理盐水;另取两种动物各8只,行胰腺腺泡细胞体外分离,用胆囊收缩素(CCK-8)刺激作为离体AP模型,对照组给予二甲基亚砜(DMSO)。观察胰腺组织病理变化、血清淀粉酶水平、胰腺组织和腺泡细胞胰蛋白酶活性和腺泡细胞淀粉酶释放率。Western blot检测胰腺组织及腺泡细胞中HSP70蛋白的表达。结果:病理学观察,两种小鼠的对照组胰腺未见异常,而AP组均出现不同程度的水肿、出血、坏死,经定量分析,KO小鼠胰腺炎腺泡细胞坏死数量和空泡数量明显少于WT小鼠(均P0.05);两对照组间胰腺组织胰蛋白酶活性和体外腺泡细胞胰蛋白酶活性无明显差异(均P0.05),但AP组(在体、离体)KO小鼠胰腺组织及腺泡的胰蛋白酶活性均低于WT小鼠(均P0.05)。两种小鼠间血清淀粉酶水平及腺泡细胞淀粉酶释放曲线差异无统计学意义(P0.05);与对照组比较,AP组(在体、离体)小鼠胰腺组织和腺泡细胞HSP70表达均增加,且KO小鼠表达量明显大于WT小鼠(均P0.05)。结论:AP时,PI3Kγ可能通过下调HSP70表达水平和增强胰蛋白酶原活化促进腺泡细胞坏死,而对淀粉酶的分泌过程无明显影响。     

缓释泵法制备急性胰腺炎大鼠模型

目的探讨利用缓释泵法模拟多因素诱导急性胰腺炎(AP)大鼠模型的相关技术。方法将75只健康SD大鼠按随机表法随机均分为缓释泵组(SRP组)、传统组(TAP组)和假手术组(SO组),TAP组采用胆胰管逆行注射法,SRP组应用缓释泵注射4%牛磺胆酸钠,从自我消化、梗阻、细胞因子激活等多方面机理模拟AP发病机理;3组大鼠均在模型诱导后1、6、12及24 h后检测血清淀粉酶及胰腺组织髓过氧化物酶(MPO)水平,观察胰腺组织病理学改变,并进行胰腺病变程度评分。结果 在模型诱导后1、6、12及24 h,SRP组和TAP组大鼠的血清淀粉酶及MPO水平和胰腺病变程度评分均明显高于SO组(P<0.05或P<0.01),而SRP组各时点的胰腺病变程度评分以及血清淀粉酶和胰腺组织中MPO水平升高程度均较TAP组低,上升趋势相对较缓,其中6和12 h的差异有统计学意义(P<0.05或P<0.01)。结论 缓释泵法可成功诱导AP,该方法可从增加胰管内压、导致组织水肿、持续释放炎症刺激因子等多层面模拟胰腺炎病理生理过程,通过留置泵可进一步监测、控制胰管内压或用于进一步治疗。缓释泵法作用相对较缓,造模过程相对容易管理,死亡率较低。     

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.     

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.     

Intravenous endotoxin does not increase tissue extravasation of albumin in rats

Background : It is unclear whether activation of the inducible nitric oxide synthase (iNOS) increases or decreases the extravasation of plasma.
Methods : Chloralose anaesthetised male Wistar rats received E. coli lipopolysacharide (LPS), 3 mg kg^-1 i.v., or the corresponding volume of saline, 3 or 5 h before the end of the experiment. Mean arterial pressure (MAP) and heart rate (HR) were recorded. Tissue clearance of radio-labelled albumin, during the last 2 h of each experiment, was determined by a double-isotope method. In separate animals, the serum concentration of nitrite and nitrate was determined, 5 h after LPS or the solvent.
Main Results : LPS initially decreased MAP and lastingly increased HR. In the 3-h LPS animals (n=8), tissue plasma clearance was lower in the heart and calf muscle and increased only in diaphragm, compared to corresponding control animals (n=8). In the 5-h LPS rats, clearance was lowered (n=8) in the entire gastrointestinal tract and in testes, compared to controls (n=8). The serum nitrite/nitrate concentration was higher in animals given LPS (n=6) than in controls (n=6).
Conclusion : After LPS, tissue clearance of albumin was not increased in any major tissue, in spite of increased serum levels of NO end products. Apparently, after activation of iNOS, the augmented release of NO is not necessarily associated with increased albumin extravasation.