肝脏胞外基质成分参与卵圆细胞介导的肝再生

目的 探讨肝再生中肝脏胞外基质成分与卵圆细胞的相互关系及作用.方法 采用免疫组化及免疫荧光双标的方法动态观察大鼠卵圆细胞增殖模型中肝脏胞外基质成分(层粘连蛋白和纤维连接蛋白)的定位及与卵圆细胞的关系. 结果 肝部分切除后第2天,卵圆细胞开始向门静脉周围区域增殖.层粘连蛋白主要出现在门静脉周围的肝窦状隙内,纤维连接蛋白在整个肝小叶内表达显著增加.术后第4～9天,卵圆细胞进一步向肝实质内增殖,门静脉周围纤维连接蛋白表达增加,中央静脉周围表达减少.层粘连蛋白及纤维连接蛋白与卵圆细胞关系紧密.术后第12～15天,随着卵圆细胞分化为小肝细胞结节,大多数层粘连蛋白及纤维连接蛋白位于结节周边,少数出现在结节内.第18天以后,正常的肝小叶结构开始恢复.结论 卵圆细胞与肝脏胞外基质成分存在紧密联系;局部肝脏微环境可能通过细胞与基质之间的相互作用在卵圆细胞介导的肝再生中发挥重要的调控作用.     

大鼠肝卵圆细胞的分离培养及干细胞标志分析

目的研究简单易行的成体大鼠肝卵圆细胞的分离培养及干细胞鉴定方法。方法采用2-乙酰氨基芴/部分肝切除术刺激建立成体大鼠肝卵圆细胞增殖模型,于肝切除术后第12d切取剩余肝脏,使用胶原酶Ⅳ消化分离和Percoll梯度离心纯化肝卵圆细胞,免疫荧光技术和RT-PCR分析法检测肝卵圆细胞标志物mRNA表达。结果分离得到的肝卵圆细胞存活率达到90%,经c-kit免疫荧光显色,PCR分析显示有CK19和白蛋白mRNA表达。生长因子诱导下有向胆管细胞和肝细胞分化的特性。结论简单易行的肝卵圆细胞分离纯化及鉴定方法和肝卵圆细胞成功培养,为进一步研究肝干细胞生物学特性和与肝癌的关系提供了物质基础。     

大鼠2-乙酰胺基芴/部分肝切除模型中卵圆细胞增殖动力学的初步研究

目的 研究大鼠肝脏卵圆细胞增殖模型中卵圆细胞增殖率的变化,进一步了解卵圆细胞生物学特性.方法 采用2-乙酰胺基芴/部分肝切除(2-AAF/PH)的方法建立大鼠肝卵圆细胞增殖模型.免疫荧光双标技术检测肝切除术后不同时间点肝脏石蜡切片中卵圆细胞标志物上皮细胞黏附分子和增殖标志物增殖细胞核抗原的共表达情况,对阳性细胞进行定量计数分析;并采用荧光双标和天狼猩红染色观察此过程中肝星状细胞激活和肝脏胶原沉积的情况.结果 术后第2天门静脉区开始出现少量卵圆细胞,到第9天数量达到高峰,此后数量逐步下降.此过程中卵圆细胞的增殖率逐步下降,从第2天的(91.3±1.6)%下降到第12天的(53.6±4.4)%,差异有统计学意义(P＜0.01).激活的肝星状细胞一直伴随卵圆细胞增殖并向肝实质延伸,分泌的胶原形成细胞外基质包绕小管样结构的卵圆细胞.结论 2-AAF/PH模型中卵圆细胞数量达到高峰前,其增殖率已经开始逐渐下降.肝星状细胞可能通过分泌细胞外基质和多种因子严格调控卵圆细胞的增殖.     

硫氧还蛋白2在2-乙酰氨基芴加肝切除诱导的卵圆细胞中的表达及意义

目的 观察硫氧还蛋白2(Trx2)在2-乙酰氨基芴(2-AAF)加肝切除诱导的卵圆细胞增殖中的表达,并探讨其表达的意义.方法 Balb/c小鼠喂饲2-AAF加2/3肝切除方法诱导肝脏卵圆细胞的增殖.经门静脉灌注消化法和等密度离心法分离卵圆细胞,并在体外进行原代培养.免疫荧光和双标法对培养的细胞进行鉴定.免疫组化法检测卵圆细胞的增殖,免疫荧光法检测Trx2在卵圆细胞和肝实质细胞中的表达,TUNEL法检测卵圆细胞和肝实质细胞的凋亡.结果 喂饲2-AAF后引起肝脏损伤,与肝切除前相比,肝切除后肝脏损伤明显加重(P＜0.01),同时有明显的卵圆细胞增殖.卵圆细胞中Trx2的表达明显高于肝实质细胞,同时其凋亡率明显低于肝实质细胞(P＜0.01).结论 喂饲2-AAF加2/3肝切除可以引起严重的肝损伤,促进卵圆细胞增殖,卵圆细胞高表达Trx2可以抑制自身凋亡和损伤,在肝脏功能的恢复过程中起着非常重要的作用.     

成体小鼠肝脏卵圆细胞的分离及培养

目的:建立一种稳定的成体小鼠卵圆细胞的分离和培养方法。方法:采用喂饲2-乙酰氨基芴（AAF）加2/3肝切除方法诱导肝脏卵圆细胞的增殖。经门静脉灌注消化法和等密度离心法分离卵圆细胞，并在体外进行长期培养。免疫荧光和免疫双标法对培养的卵圆细胞加以鉴定。结果:体外培养的卵圆细胞呈集落样生长，稳定传代并已培养至3个月。免疫荧光和免疫双标法证实培养的细胞为卵圆细胞，并显示该细胞具有分化潜能。结论:该方法是一种稳定的成体小鼠卵圆细胞的分离和培养方法，为肝脏干细胞的相关研究和应用奠定基础。     

大鼠肝卵圆细胞与肝星状细胞在2-AAF/PH模型中的增殖及关系研究

目的 研究大鼠肝卵圆细胞与肝星状细胞增殖过程中关系,探讨肝星状细胞(HSCs)对卵圆细胞增殖分化的调控作用.方法 利用2-乙酰氨基芴/部分肝切除(2-AAF/PH)建立大鼠肝卵圆细胞增殖模型,对术后不同时间点的肝组织标本进行常规组织学观察,并用卵圆细胞标志物OV-6和HSCs激活标志物desmin进行免疫组化染色和免疫荧光双标,对阳性细胞进行半定量计数并分析两者相关性.结果 PH后第2天,门静脉区域开始出现小管样结构的卵圆细胞和HSCs增殖;PH后第4～6天,HSCs形成网格状伴随卵圆细胞迅速增殖,向肝实质内侵入;PH后第9天,HSCs与卵圆细胞增殖达到顶峰;PH后第12～15天,出现新生小肝细胞结节及小肠样化生,HSCs随卵圆细胞显著减少,位于小肝细胞结节周围,结节内有少量HSCs;PH后第18～21天,HSCs与卵圆细胞进一步减少或消失.直线相关分析表明两者高度相关.结论 HSCs参与了肝卵圆细胞介导的肝再生,可能通过产生多种生长因子以及重塑胞外基质对卵圆细胞的增殖分化具有重要的调控作用.     

大鼠肝卵圆细胞中matrilin-2的表达及其意义

目的探讨大鼠肝脏再生过程中肝卵圆细胞matrilin-2的表达及其意义。方法利用大鼠部分肝切除(PH)或2-乙酰氨基芴灌胃+/部分肝切除(2-AAF/PH)建立大鼠肝脏再生模型,并设正常对照组。应用免疫组织化学和RT-PCR方法研究肝脏组织中matrilin-2表达情况。结果免疫组化发现正常对照组及PH组肝脏组织中只有极少量的matrilin-2表达位于胆管血管周围及肝窦状隙内,而在2-AAF/PH模型中可见matrilin-2表达位于门静脉周围的肝窦状隙内,RT-PCR发现2-AAF/PH组肝卵圆细胞中matrilin-2mRNA高表达,而PH组及正常对照组成熟肝细胞中无matrilin-2mRNA表达。结论matrilin-2是肝卵圆细胞在肝脏再生过程中产生的重要的细胞外基质蛋白,与肝卵圆细胞的增殖分化过程有密切关系。     

miR-21调节缺血缺氧诱导的大鼠肝卵圆细胞自噬的研究

目的探讨miR-21在缺血缺氧诱导的大鼠肝卵圆细胞自噬中的作用。方法体外培养肝卵圆细胞,慢病毒转染肝卵圆细胞构建稳定的细胞株,分别提取各组细胞RNA逆转录后行SYBR Green实时荧光定量PCR,检测各组miR-21的表达,以转染好的稳定的细胞建立缺血缺氧模型,共分为3组:miR-21空载体慢病毒转染HOC自噬组,miR-21增强慢病毒载体转染HOC自噬组,miR-21-inhibition慢病毒载体转染HOC自噬组。Hoechst 33258染色观察细胞凋亡;应用丹(磺)酰戊二胺(Monodansylcadaverine,MDC)染色荧光定位法、观察各组细胞的自噬;免疫印迹法(Western blotting)检测各组细胞LC3-Ⅱ/Ⅰ蛋白表达情况。结果与空载体组比,增强组miR-21基因水平表达增强,而MDC染色减弱(自噬减少),蛋白LC3-Ⅱ/LC3-Ⅰ的比值减少;而抑制组miR-21基因水平表达减少,MDC染色增强(自噬增强),蛋白LC3-Ⅱ/LC3-Ⅰ的比值增多。结论抑制miR-21过表达可以增强缺血缺氧引起的肝卵圆细胞的自噬,有利于肝卵圆细胞在缺血缺氧微环境中稳定细胞内环境,维持细胞的存活。     

肝卵圆细胞对大鼠肝硬化组织TGFβ/smad信号传导的影响

【摘要】〓目的〓探讨肝卵圆细胞对TGFβ/smad信号传导通路影响的机制,并证明肝卵圆细胞对肝硬化的发展是否有阻止和逆转的作用。方法〓对肝卵圆细胞进行增殖、分离、培养后,移植于肝硬化大鼠肝脏组织,以未经移植的大鼠做对照,分别进行组织病理学和肝功能及蛋白表达水平的检测,分析ALB、AST、ALT、TGFβ1、TGFβRⅡ、Smad2、Smad4 、Smad7的情况。结果〓移植肝卵圆细胞的鼠肝硬化组织纤维化减少,肝功能明显改善(P<0.05),肝硬化组织TGFβ/smad信号通路中各蛋白表达量有差异。结论〓肝卵圆细胞刺激肝硬化细胞后TGFβ/smad信号通路中各蛋白的表达是不同的,肝卵圆细胞对肝硬化组织有阻止和逆转的作用。     

大鼠肝卵圆细胞的分离培养和体外分化研究

目的 观察大鼠肝卵圆细胞的活化，为进一步研究肝卵圆细胞特征建立简单的分离培养方法。方法 利用2-乙酰氨基笏／部分肝切除建立肝卵圆细胞活化的大鼠模型，采用选择性消化法从该模型中分离纯化肝卵圆细胞，并做免疫细胞荧光鉴定。用丁酸钠诱导其分化。结果 成功地建立了肝卵圆细胞活化模型，并从中分离培养了表达OV6、CK19、AFP、白蛋白、c-kit、Thy1、CD45和CD34的卵圆细胞。在丁酸钠刺激下它可向肝细胞分化。结论 利用选择性消化法可以分离到肝卵圆细胞，并且其具有肝干细胞的特征。     

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.     

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.     

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.     

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.