鼠外周血内皮祖细胞体外培养鉴定与诱导分化

目的探讨鼠外周血来源的血管内皮祖细胞(EPCs)体外培养鉴定及诱导分化的方法。方法从鼠外周血中分离获取EPCs,进行体外培养扩增,并在培养液中添加VEGF及bFGF,采用免疫组织化学技术和流式细胞仪进行EPCs的细胞表面标志物检测。结果培养3~4d,可观察到梭形贴壁细胞,14d左右贴壁细胞呈条索状结构,贴壁细胞是表达血管内皮细胞的特异性标志。结论鼠外周血中含有EPCs,在一定条件下,可分化成血管内皮细胞。     

大鼠骨髓来源的血管内皮祖细胞的体外培养和鉴定

目的探索大鼠骨髓来源的血管内皮祖细胞（EPCs）的体外培养、诱导分化及鉴定方法。方法采用密度梯度离心法从Wistar大鼠骨髓中分离出骨髓单个核细胞,并在诱导培养基（EGM-2MV）中培养,贴壁筛选法分离,诱导分化为EPCs;观察EPCs的生长分化过程,对其形态、表型、功能加以鉴定。结果培养3 d,细胞贴壁较为完全,第4天换液后,细胞呈现克隆样生长,第7～8天形成类似成熟血管内皮细胞形态,呈现典型的"铺路石"样外观;诱导培养第7、10天的贴壁细胞CD34、Flk-1及CDl33染色均呈阳性;荧光显微镜下观察,DIL-ac-LDL和FITC-UEA-1双荧光染色的细胞数占贴壁细胞数的75%以上。结论采用密度梯度离心法获得骨髓单个核细胞,在培养液中贴壁培养,可以扩增出具有典型特征的EPCs。     

人外周血内皮祖细胞培养及特性

目的 探讨人外周血来源的内皮祖细胞(EPCs)体外诱导培养和扩增的方法，以期证实人外周血是临床治疗缺血性疾病一个理想的内皮祖细胞来源。方法 采集正常人外周血单个核细胞进行体外培养，应用免疫组织化学和免疫荧光技术进行内皮细胞表面标记物检测，应用细胞荧光化学检测进行培养细胞的内皮细胞功能检测。结果 人外周血单个核细胞(MNCs)经体外培养，表达内皮细胞的特异性抗原，包括Ⅷ因子(VWF)、FLK-1、CD31和CD34，并显示出能内吞乙酰低密度脂蛋白(acLDL)，结合UEA-1等内皮细胞的特性，提示这些培养细胞具有内皮细胞的表面蛋白特性和具有内皮细胞的功能。结论 人外周血中存在具有分化增殖能力的EPCs，可体外扩增和收集。     

外周血早晚期内皮祖细胞的生物学特性及鉴定的初步研究

目的通过人外周血分离培养早晚期内皮祖细胞(endothelial progenitor cells,EPCs),比较两类EPCs的特性,以期找到可靠的稳定生物学表征及鉴定方法鉴定EPCs。方法通过密度梯度离心法分离人外周血单核细胞,体外种植于内皮细胞全培养基诱导培养,分别于培养4~7 d及2~3周获得早、晚期EPCs。对两类EPCs的细胞形态、增殖能力、细胞表型、细胞因子表达情况、体外成血管能力及一氧化氮(nitric oxide,NO)释放能力进行检测比较,并以成熟人主动脉内皮细胞(human aortic endothelial cells,HAECs)作为阳性对照。结果两类EPCs形态不同,早期EPCs形成纺锤样细胞簇,而晚期EPCs呈鹅卵石样外观;晚期EPCs具有高增殖潜能,可在基质胶上形成毛细管状结构,而早期EPCs则不具备该特性;两类EPCs均可摄取乙酰化低密度脂蛋白,并能与荆豆凝集素Ⅰ结合;流式细胞仪检测发现早期EPCs不表达CD34和CD133,但造血干细胞标记CD14和CD45表达却呈阳性,而晚期EPCs对于内皮型表面标记CD31和CD34表现为强阳性,但CD14、CD45、CD133表达则呈阴性。RTPCR分析发现早期EPCs的血管内皮生长因子受体2及血管内皮钙黏蛋白基因的相对表达量显著低于晚期EPCs及HAECs(P0.05),而血管性血友病因子及内皮型一氧化氮合成酶(endothelial nitric oxide synthase,eNOS)基因的相对表达量比较差异无统计学意义(P0.05)。细胞因子分泌方面,早期EPCs培养上清液中的VEGF、粒细胞集落刺激因子及IL-8浓度明显高于晚期EPCs(P0.05)。Western blot检测示,两类EPCs均表达eNOS,但培养5周的晚期EPCs的eNOS表达水平高于早期EPCs(P0.05);两种EPCs均可释放NO,但NO产量差异无统计学意义(P0.05)。结论 eNOS的表达及NO释放能力作为内皮细胞的可靠生物学特征可用于EPCs鉴别,多方法联合方式用于鉴定EPCs更为可行。     

大鼠脐血来源单个核细胞诱导为内皮祖细胞的免疫荧光检测

目的脐血（umbilical cord blood,UCB）中含有大量内皮祖细胞（endothelial progenitor cells,EPCs）,内皮祖细胞（EPCs）是血管内皮细胞的前体细胞,有分化为血管内皮细胞的能力,为骨组织工程血管化带来新的途径。本实验研究大鼠脐血来源的单个核细胞体外诱导为EPCs的可能性。方法分离大鼠脐血单个核细胞,血管内皮诱导液（添加10％胎牛血清,1％青霉素,1％链霉素,VEGF20ug／L,IGF-12ug／L,bFGF2ug／L,EGF20ug／L）培养分化,于3周、6周进行免疫荧光染色检测贴壁细胞CD34、CD133、Flk-1、vWF表面标志。结果培养三周单个核细胞CD34、CD133、Flk-1、vWF抗体免疫荧光检测均为阳性;六周免疫荧光染色可见CD34、Flk-1、VWF组为阳性,CD133组部分为阳性,阴性对照组未发现阳性细胞。结论大鼠脐血来源的单个核细胞在体外诱导3周可以分化为EPCs,6周部分细胞分化为成熟血管内皮细胞。     

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。     

人骨髓内皮祖细胞的分离、诱导培养和扩增

目的 探讨并改进从人骨髓中分离、诱导培养和体外扩增内皮祖细胞(EPCs)的方法 ,为EPCs参与基础研究和临床应用奠定基础. 方法 采用不同的细胞分离液,用密度梯度离心法从正常人骨髓中分离单个核细胞(hBMMNCs),分别培养在包被人纤维连接蛋白(HFN包被组),包被明胶(明胶包被组)和未包被(未包被组)的培养皿内,利用EBM-2培养4～7 d后出现细胞克隆集落(cell colony-forming units,CFUs),挑选内皮祖细胞样CFUs继续培养(CFUs挑选法),采用流式细胞仪检测CD34 KDR 和CDl33 KDR 双荧光阳性细胞,细胞免疫化学法检测EPCs表面标记CD133、CD34、CD31、vWF和KDR的表达. 结果 用OptiprepTM分离液可从人骨髓中更有效地分离出hBMMNCs,进而诱导获取更多EPCs并可进行体外培养扩增;流式细胞仪检测结果 显示CD133 KDR 细胞高达70.4%±5.4%,CD34 KDR 细胞高达69.1%±8.7%;HFN包被组和明胶包被组细胞生长一样旺盛,均可促进EPCs的贴壁生长,促进其生长的作用差异无统计学意义(P＞0.05),而未包被组细胞生长数量最少.培养7d的贴壁细胞表面标记CD133、CD31、vWF和KDR均呈阳性,培养14d的贴壁细胞表面标记CD34呈阳性. 结论 CFUs挑选法可以从人骨髓中成功地获取更多EPCs并在体外扩增,提出了另一种获取EPCs的高效简单方法 ,进一步拓宽了获取EPCs的方法 和范围.     

兔外周血内皮祖细胞的分离培养及鉴定

内皮细胞(EC)构成正常的血管壁,内皮祖细胞(EPCs)是EC的前体细胞,可在体内、外分化为成熟EC。本研究以新西兰兔外周血为研究对象,探索分离、培养、扩增EPCs的方法,以期为细胞治疗为主的血管性疾病治疗提供实验基础。     

人VEGF165基因转染人外周血内皮祖细胞的实验研究

目的 探讨人血管内皮细胞生长因子165(hVEGF165)基因转染对人外周血内皮祖细胞(EPCs)的影响.方法 体外分离、培养、鉴定人外周血EPCs.实验分脂质体介导pcDNA3.1-hVEGF165质粒转染组,pcDNA3.1空质粒转染组,窄白对照组.ELISA法和硝酸还原酶法分别测定各组上清液中VEGF和一氧化氮(NO)的含量;噻唑蓝(MTT)检测它们对EPCs增殖的影响.结果 FITC-UEA-I和DiI-ac-LDL双染色阳性细胞为正在分化的EPCs,脂质体介导pcDNA3.1-hVEGF165质粒转染组EPCs培养基上清液中VEGF和NO表达量明显高于其他两组(P＜0.01);VEGF质粒转染对EPCs的增殖无明显影响.结论 人外周血EPCs可以成功转染hVEGF165基因.同时能表达一定浓度的VEGF蛋白,并可促进NO的分泌,而对EPCs的活性无明显影响.该研究为进一步研究VEGF165基因和EPCs结合治疗缺血性疾病提供了实验依据.     

内皮祖细胞在肾癌中的研究进展

内皮祖细胞(Endothelial progenitor cells,EPCs)主要来源于骨髓,是内皮细胞的前体细胞,多种因素可动员EPCs入外周血参与血管新生.因此,EPCs有可能成为一种抑制肿瘤血管生成的靶向载体,在肾癌治疗中正引起人们的关注.本文就EPCs在肾癌中的研究进展进行了综述.     

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.     

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.     

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.