鼠骨组织成骨细胞的离体培养和生长特性

目的：观察大鼠骨组织来源成骨细胞的体外分离培养的条件及生长特征，为骨组织工程学实验研究奠定基础。方法；取出生24hSD乳鼠的顶骨，酶经法分离培养成骨细胞并传代，观察其生物学特征，并进行ALP活性测定，绘制生长曲线、分裂指数曲线和贴壁率曲线、测定细胞贴壁及延展时间。并将培养细胞进行冻存、复苏、比较细胞特性有无改变。结果：培养细胞在第8代以前生长性状稳定，具有典型的成骨细胞特性，可作为实验细胞；第4d为细胞生长倍增时间，第5－6d细胞达生长高峰；第4d细胞分裂最为旺盛，达18％；传代后10h贴壁率最高，为90％；冻存复苏后的细胞生物学特性无改变。结论：本实验方法体外培养的成骨细胞，生长性状稳定，增殖速度快，具有与体内成骨细胞相同的生物学特性，保证了相关实验的可靠性和准确性，可作为骨组织工程学研究的种子细胞。     

冻存对人脐血间充质干细胞生物学特性的影响

目的观察冻存复苏对人脐血（human umbili calcord blood）间充质干细胞（mesenchymal stem cells，MSCs）生物学特性的影响。方法体外分离、培养人脐血MSCs，传代后，将第3代的MSCs加入含10％二甲基亚砜（DMSO）和90％胎牛血清的细胞冻存液中，-196℃液氮保存4周，观察比较冻存前及冻存复苏后MSCs的形态、增殖及多向分化能力。结果冻存前及冻存复苏后，MSCs形态无明显差别，均呈典型的梭形，MSCs贴壁生长；MSCs生长曲线相似，冻存复苏后的细胞生长曲线略有下降，但差异无统计学意义（P〉0．05）；MSCs经脂肪诱导液诱导2周后，细胞浆中出现脂肪细胞所特有的脂肪滴，经0．5％油红0染色，脂肪滴染为红色，说明MSCs有向脂肪细胞分化的能力；Mscs经成骨诱导液诱导4周后，VonKossa染色可见黑色的矿化结节沉积，钙结节的形成为成骨细胞特有，说明Mscs有向成骨细胞分化的能力。提示冻存复苏后Mscs经诱导仍然可以向脂肪细胞和成骨细胞分化，与冻存前无明显差异。结论人脐血MSCs经冻存复苏后，其生物学特性可获良好保持。     

大鼠骨髓基质细胞的体外培养

目的：观察大鼠骨髓基质细胞在体外培养的条件,为骨组织工程学研究奠定一定实验基础。方法：取幼年SD大鼠,处死后分离骨髓,原代培养骨髓基质细胞,传代后分别观察其生长特性,绘制生长曲线,测定分裂指数和贴壁率。结果：大鼠骨髓基质细胞在第7代以前生长形状相对稳定,生长曲线相似;第4d分裂指数最高,为16％;传代后12h贴壁率最高,为90％。结论：本实验方法中,骨髓基质细胞在体外培养条件下,早期生长性状稳定,增殖速度快,适应性强,可作为骨组织工程学研究的种子细胞。     

家兔作为胎龄期骨髓间充质干细胞动物模型的实验研究

目的建立以家兔为对象的胎龄期BMSC研究动物模型。方法通过人工授精方法,获得孕期3周的孕兔4只,行剖腹产术取出胎兔20只,冲取胎兔骨髓,以贴壁培养法进行体外扩增培养。测量第3代胎兔BMSC的生长曲线,克隆形成率,并进行成骨、成脂及成软骨诱导分化。另外,将原代细胞冻存30 d后复苏,测量其第3代生长曲线,对冻存前后增殖能力的变化进行观察。扫描电镜观察胎兔BMSC与β-TCP形成细胞材料复合物的体外形态。将BMSCs-β-TCP复合物植入裸鼠皮下,于术后1、3、6个月分别取材,行HE、VG、Masson染色观察。结果胎兔来源的BMSC于倒置相差显微镜下观察,细胞饱满均匀,呈梭形或倒三角形状;传代后各代细胞形态未发生明显变化,生长曲线相差不大;成骨、成脂以及成软骨诱导观察到钙结节、脂肪空泡、黏多糖。冻存30 d后复苏,其第3代生长曲线与冻存前相比未见明显变化。电镜下观察,与β-TCP复合7 d后,细胞能均匀紧密贴合于材料上,伸展良好分布均匀。植入裸鼠皮不同时间点取材行HE、VG、Masson染色,均显示有新生骨组织生成。结论以家兔为研究动物模型,可以在胎龄期获取并分离得到BMSC,并可在异位构建组织工程骨,是间充质干细胞动物研究的新选择。     

冻存对组织工程骨膜生物活性的影响

目的 观察冻存复苏过程对组织工程骨膜生物学特性的影响.方法 体外培养新西兰大白兔骨髓间充质干细胞(BMSCs),与猪小肠黏膜下层(SIS)构建组织工程骨膜.冻存后复苏培养,扫描电镜(SEM)观查复苏后种子细胞生长状况、噻唑蓝(MTT)比色法绘生长曲线、钙-钴法检测碱性磷酸酶(ALP)、生物化学法定量分析ALP的表达.结果 冻存复苏后BMSCs仍能在SIS上保持良好的生长状况;组织工程骨膜复苏后成骨诱导培养5d时ALP含量达峰值,10～15d时稳定在较低的量,与对照组比较差异有统计学意义(P<0.05). 结论组织工程骨膜冻存复苏后仍保持较稳定的生物活性.     

慢性粒细胞白血病患者骨髓间充质干细胞冻存后的生物学特性

目的 明确冻存对慢性粒细胞白血病(CML)患者骨髓间充质干细胞(MSC)生物学特性的影响.方法 采用细胞贴壁法获取CML患者骨髓MSC,将传代后的细胞用IMDM细胞冻存液(含质量分数为10%的二甲基亚砜和400 g/L的胎牛血清)保存在-196℃液氮中.观察短期(4周)和长期(12个月)冻存复苏后MsC的增殖能力.将冻存后CML患者骨髓MSC作为滋养层,应用甲基纤维素半固体培养,检测其支持造血的能力.混合淋巴细胞反应检测冻存后CML患者的骨髓MSC免疫抑制能力.结果 短、长期冻存后的MSC的细胞活性分别为为(94.1±1.9)%和(89.8±4.3)%;短、长期冻存后细胞的增殖能力与冻存前MSC相似;冻存后CML患者的骨髓MSC仍具有支持造血集落生长作用(CFU-GM,CFU-E,CFU-GEMM)和抑制T淋巴细胞增殖能力,与冻存前相比,没有明显差别.结论 冻存可以降低CML患者骨髓MSC的细胞活性,但是并不影响MSC的增殖、支持造血和免疫调节的能力.     

正常人与慢性牙周炎伴有骨质疏松患者牙槽骨组织培养细胞的生物学特性

目的 无菌取健康人和慢性牙周炎伴骨质疏松患者的牙槽骨组织，经体外培养，各建立一个能传代、冻存、复苏成活的种子细胞系。比较两种细胞系的生物学特性。为牙槽骨的缺损、修复、治疗提供理论和相关实验依据。方法 从原代培养出来的4个细胞系(H-171、H-258、261、262)中。选出牙周炎伴骨质疏松患者组细胞系H-171，正常组H-258，用组化、免疫组化等染色。观察细胞形态。用细胞计数法计算出两种细胞倍增时间和分裂指数。经过多次传代、冻存、复苏，比较细胞的生长、老化规律。结果 1．异常牙槽骨组，原代培养1次成功，细胞形态为短梭形，3次冻存，3次复苏均存活，其倍增时间为53．4h。平均分裂指数为4‰。细胞传代20次后，仍生长良好，以破骨细胞为主。2．健康牙槽骨组原代培养26例，因多种原因能传代的细胞系仅有3例，已传代10次，形态为长梭形，经2次冻存复苏，细胞存活、生长速度较H—171慢，倍增时间为65．9h，平均分裂指数3．5‰。3．两种细胞均贴壁生长，具有成骨细胞的特点：AKP、甲苯胺兰、PAS、四环素标记矿化结节组化染色及Ⅰ型胶原、BMP—2免疫组化染色均为阳性。结论 1．均具有成骨细胞特点。2．生长速度：H—171较H-258快，传代20次，生长活跃，H—258传到8代开始老化，生长速度减慢。     

人骨髓源性成骨细胞体外培养和生物学特性的研究

目的研究人骨髓源性成骨细胞的生物学特性,为骨组织工程选择理想的种子细胞提供依据。方法采用全骨髓培养法培养骨髓基质干细胞,传代扩增后采用诱导培养基进行诱导,对骨髓基质干细胞诱导成的成骨细胞进行细胞形态学观察,检测碱性磷酸酶活性及分泌钙结节和Ⅰ型胶原的能力。结果骨髓基质干细胞可以进行传代和大量扩增,经诱导培养后能够诱导出成骨细胞,诱导出的成骨细胞具有典型成骨细胞的形态学和生物学特性。结论骨髓源性成骨细胞具有良好的成骨细胞特性,可以作为骨组织工程的种子细胞。     

大鼠骨髓间充质干细胞的分离培养和生物学特性研究

目的 探讨体外分离培养大鼠骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)的方法,并研究其生物学特性.方法 取大鼠股骨和胫骨,以Ficoll密度梯度离心法结合贴壁法分离纯化大鼠BMSCs,传代扩增,倒置显微镜进行细胞形态学观察,MTT法测定细胞的生长曲线,流式细胞仪细胞表面抗原.结果 原代分离的BMSCs,培养48 h开始贴壁,胞体由圆形变为椭圆形、多角形或短梭型;培养第12天,见胞体渐变为长梭型,并达90%单层融合;经传代扩增,细胞进一步纯化.7代以前,细胞在2 d内处于潜伏期,第3天进入对数生长期,第7天进入平台期;10代后增殖速度变慢;流式细胞仪鉴定BMSCs表而抗原,CD44、CD90、CD34阳性率分别为99.62%、95.13%、2.06%.结论 Ficoll密度梯度离心法结合贴壁法有效分离纯化大鼠BMSCs,且细胞生长稳定,增值能力活跃,具有MSCs的一般生物学特性.     

免疫磁珠分选兔前软骨干细胞及细胞研究平台的建立

[目的]研究兔前软骨干细胞PSCs,(precartilagious stem cells)的分离、培养方法及增殖、表型特征,为细胞移植治疗椎间盘退变,提供合适的种子细胞.[方法]取胎兔骨骺周围软骨膜(LaCroix环)中的细胞进行原代培养,然后采用免疫磁珠分离系统分选纯化PSCs.体外培养,传代,冻存复苏,绘制生长曲线,观察细胞特性.分别采用免疫组化、免疫荧光、RT-PCR等方法鉴定纯化后的PSCs.[结果]免疫磁珠分离可获得纯度较高的兔PSCs,培养后成活率高,细胞状态良好.细胞冻存复苏后,细胞增殖速度、细胞形态及表面标志物无明显变化.免疫组化、免疫荧光、RT-PCR等方法鉴定后,细胞都有明显的PSCs表面特异性标记物的表达.[结论]PSCs存在于LaCroix环中,免疫磁珠分离法得到的PSCs,体外培养条件下,细胞增殖较快,生物学特性稳定.     

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.