自体骨髓移植治疗兔Perthes病模型的实验研究

目的：研究自体骨髓移植治疗兔Perthes病模型的结果。方法：抽取5－7ml自体骨髓，结合钻孔减压植入Perthes病模型。结果：自骨髓移植组坏死骨昨较空白对照的活跃，骺后伤处可见少量软骨细胞，单纯钻孔组以纤维修复为主，结论：自体骨髓移植治疗兔Perthes病模型的坏死骨修复有一定的帮助，但不能修复钻也所造成的骺板损伤。     

不同颈椎内固定融合术式实验兔模型的建立

目的建立兔颈椎不同术式内固定融合模型。方法将60只新西兰白兔随机分3组,每组20只。A组行颈椎前路椎体间融合内固定术,B组行颈椎后路椎板棘突间融合内固定术,C组行颈椎前、后路联合融合内固定术。造模后1个月和3个月,每组10只行安乐死取材,分别摄X线片、作大体及组织形态学观察。结果随着时间的推移,X线片可见A、C组固定节段椎间隙逐渐融合、消失,B、C组固定节段椎板棘突融合。术后1个月标本见骨小梁、胶原纤维排列有序、规则,骨外膜侧尚有部分纤维组织,表明其有骨化及成骨现象;术后3个月标本见类似于正常椎体骨或椎板骨,胶原纤维折光性强,方向有序。结论建立兔颈椎内固定融合模型方法简单、易行、可靠,为脊柱疾病治疗方法研究提供良好的平台。     

International Normalized Ratio：青年脑梗死危险因素

目的评估入院时国际标准化比值水平对青年脑梗死患者出院时短期预后的影响。方法分析585例患腑梗死的青年患者，这些患者从来未服用华法令。所有患者都在发病48h后入院，脑影像学检查（CI、或者MRI）仲入院后24～48h后进行。结果通过logistic回归模型，笔者发现较高的INR和纤维蛋门原水平预永着患者在入院时有较差的预后。结论应用该回归分析模型，笔者确定INR足青年脑梗死患者临床预后的独立危险因素，因此入院时INR的水平不仅仅是凝血功能检测的指标，而且将为青年脑梗死患者提供一个实用的临床预后信息。     

经颅多谱勒检测兔大脑中动脉微血栓栓子的研究

目的应用经颅多谱勒（TCD）动态检测兔血栓栓塞模型大脑中动脉（MCA）的微栓子信号（MES），观察栓子的负荷量与缺血性脑血管病（ICVD）发生的相关性。方法将实验动物随机分为3组，即A组含3—5个栓子，B组含6-10个栓子，C组为生理盐水对照组。采用自体动脉血微栓子建立兔局灶性脑缺血模型同时TCD监测MES。栓塞后6h进行磁共振成像（MRI）及兔脑组织病理观察。结果A、B组TCD均监测到MES；B组MRI的T1WI、T2WI及病理观察见梗死灶，而A组仅在弥散加权成像（DWI）见可疑小缺血灶。结论TCD实时、动态观察微栓子信号，能预测缺血性脑血管病发生的危险性，为临床及早干预治疗提供科学依据。     

带血运骨膜管移植和骨充填物修复桡骨长段缺损的研究

目的：探讨联合应用带血运骨膜管移植和骨充填物治疗兔桡骨长段缺损的效果。方法：实验分两部分，分别选用幼兔和成年兔各40只，根据填充物的不同分为4组，将兔双侧桡骨干中段切除3cm制成骨长段缺损模型，保留切骨段骨膜，重新重原缝合后作带血运骨膜管移植模型，左侧分别用自体骨，同种异体脱钙骨，磷酸三钙陶瓷和羟基磷灰石进行填充，右侧不行任何填作为对照。观察3个月。通过X线片，髓强度，骨密度和组织学检查等方法，了解骨缺损的修复效果。结果：幼兔术后6周，所有实验组双侧的骨缺损均得到修复，术后12周，磷酸三钙陶瓷和羟基磷灰石组桡骨抗弯曲强度较差与自体骨组、同种异体脱钙骨组和对照侧比较具有统计学意义（P＜0．05）；骨愈合为膜内成骨和软骨成骨，以膜内成骨为主，成年兔；各组实验侧骨缺损修复率分别为：自体骨组50％；同种异体脱钙骨组40％；磷酸三钙陶瓷和羟基磷灰石组为30％。对照侧骨缺损修复率为42．5％，结论：幼兔单行单血运骨管移植或结合应用骨充填物均可有效修复骨长段缺损，但置换较慢的骨充填物不利于再生骨强度的恢复，成年兔带血运骨膜移植联合应用骨填充物不能有效修复骨长段缺损。     

大鼠脑梗死后48小时移植入胚胎干细胞的存活和分化

目的 观察小鼠胚胎干细胞,在大鼠脑梗死发生48 h后移植人梗死核心区,是否能够存活并且分化为神经元和胶质细胞.方法 小鼠胚胎干细胞去除滋养层后培养,线栓法制作大鼠大脑中动脉堵塞脑梗死模型,成模48 h后将胚胎干细胞移植入梗死核心区.移植21 d后切片观察.结果 植入的胚胎干细胞可在梗死区的边缘存活,并且大量分化成为神经元和胶质细胞,植入细胞所分化出的神经细胞中,表达NeuN和胶质纤维酸性蛋白(GFAP)的神经元和胶质细胞的比例分别达到(83.0±3.2)%和(22.0±3.6)%.结论 在脑梗死后48 h于核心区植入胚胎干细胞可能成为新的移植方式.     

NGF治疗兔骨筋膜室综合征神经损伤的作用研究

目的制作家兔小腿骨筋膜室综合征动物模型,早期使用神经生长因子(nerve growth factor,NGF)进行神经保护和修复,来实现对骨筋膜室综合征神经损伤的早期治疗。方法实验于2016年9月至2017年12月在南通大学动物实验室完成。24只家兔分为三组:对照组8只,损伤未注射NGF组8只,损伤注射NGF组8只。采用止血带法制作筋膜室综合征动物模型,用止血带紧密包扎家兔一侧小腿8h后松解。测量松开止血带后4h、8h、1d、3d、5d、7d、2周、4周的兔腿间隔筋膜室内压力。通过蛋白印迹试验,了解兔骨筋膜室综合征神经损伤后的神经细胞增殖变化。损伤注射组在模型制作成功后立即局部注射神经生长因子,2mL生理盐水溶解后肌肉注射,每次30μg,一天一次,连续4周。采集实验兔(对照组)、损伤后5d(损伤未注射组)、损伤后5d(损伤注射组)的兔后腿神经标本,分别进行免疫荧光实验,HE染色分析。结果松开止血带后,伤侧小腿迅速肿胀,在4h后筋膜室内压已达到(2.0±0.2)kPa以上.并在1d后达到峰值,之后逐渐下降。Western blot显示,PCNA在对照组呈现出低表达,在兔骨筋膜室综合征4h后开始上调,5d时表达达到最高峰(P0.05),然后,PCNA逐渐下降。HE染色发现:未注射NGF组在损伤后5d,可见神经纤维断裂、水肿、空泡、形状不规则的组织形态,而给予NGF注射的实验组在同一时间点的组织形态要明显好于未注射组。荧光双标显示结果表明兔骨筋膜室综合征后注射NGF可促进神经的恢复,可以通过增加早期施旺细胞增殖来实现。结论该模型能较好的模拟临床实际,病理指标的变化能客观地反映病情严重程度,证明骨筋膜室综合征早期即可发生神经损伤。早期局部应用NGF对骨筋膜室综合征神经损伤的治疗具有明显作用。     

组织隔离法与机械活动法在兔胫骨骨不连模型建立中的作用

目的 评价组织隔离法与机械活动法在建立兔胫骨萎缩型与肥大型骨不连模型中的作用方法将l2只体重为3～4．5kg的新西兰大白兔随机分成A、B两组，A组于胫骨中段截骨，两断端套接1cm硅胶管，单侧外固定器固定，保持两断端间距2mm，8周取出硅胶管，观察组织隔离法构建萎缩型骨不连模型的效果。B组于胫骨中段截骨后采用2枚1mm克氏针行髓内松动固定，被动活动断端200次／天，持续1个月，观察机械活动法构建肥大型骨不连模型的效果。结果 A组中所有动物在硅胶管取出后4周，无1例断端出现骨愈合表脱，X线片显示良好萎缩型骨不连的复制。B组中所有动物存6周内截骨端出现延迟愈合，部分伴有畸形．骨断端有人量肥大骨痂形成。结论 硅胶管组织隔离法是复制兔胫骨萎缩型骨不连模型的有效方法，而采用被动机械活动复制兔胫骨肥大型骨不连模型的方法尚需进一步研究。     

山羊骨组织内抗生素缓释模型的建立及评估

目的 建立山羊股骨远端骨洞模型,观察万古霉素缓释微球在模型体内释放药物的过程.方法 山羊双侧股骨远端形成两个圆柱形骨洞,PMMA封闭14 d后,再次暴露骨洞,分别在右侧和左侧移植万古霉素微球和无万古霉素的微球.通过高效液相检测各部位的万古霉素浓度,并以葡萄球菌作为检测菌株,评估其抗菌活性.结果 X线见骨洞约为2.5 cm×1.5 cm×1.5 cm,移植微球后右侧骨洞内的万古霉素浓度最高,1 d达最高值(294.71±20.45)mg/L;左侧和血液中的浓度在2 d达高峰,为(5.54±0.97)mg/L和(29.98±2.61)mg/L;超过对葡萄球菌敏感折点值(5 mg/L)的持续释放天数分别为21、1、6 d.结论 建立的山羊股骨远端骨洞模型适合于观察药物缓释载体在骨组织内释放药物的动态过程,便于检测洗脱出的药物浓度.     

一种新的兔椎体成形术穿刺模型建立与评价

【摘要】 目的：通过对兔脊柱解剖形态的测量及分析,建立一种新的兔椎体成形术穿刺模型,并通过术后影像学及形态学分析,评估该模型建立方法的有效性和安全性。方法：选用26只健康新西兰兔（体重2.5~3.0kg）,测量其中6只兔腰椎标本形态及其参数：L1~L7椎体高度、椎体基底宽度、椎间盘上缘距椎体最狭部距离、脊椎乳突垂直线距椎间盘上缘距离、脊椎副突下缘至椎体后缘距离,以明确兔椎体解剖特点,确定骨水泥注射的最佳位置、注射方向以及注射深度后对20只兔L5、L6椎体建立椎体成形术用穿刺模型。术后3d处死后行影像学及组织学切片检查,术后8周以及12周后分批处死行影像学检查,主要观测指标包括：手术时间,术后植入骨水泥分布,椎管及椎体前缘完整性。结果：通过兔解剖观测,椎体高度从L1~L5逐渐增大,从L5~L7逐渐减小,椎体基底部宽度从L1~L7逐渐增大。脊椎乳突中点和椎间盘上缘的距离由L1~L6逐渐增加（1.7~2.5mm）。脊柱副突下缘与椎管前壁距离由L1~L6逐渐增加（-0.2~1.3mm）,相同节段每只兔脊椎乳突与椎间盘上缘（P=0.736）和副突与椎体后缘距离之间（P=0.611）无明显统计学差异。以脊椎乳突中点垂线与脊椎副突下缘水平线交点为穿刺点,置入方向和水平面呈20°~30°角,头倾方向0~10°,穿刺深度7~10mm可以构建兔椎体穿刺手术模型。术后未出现因脊髓损伤造成下肢瘫痪,1只兔因术后感染死亡,手术时间平均为40.8±5.9min（30~55min）。术后3d组织学检查示骨水泥材料植入骨小梁内,椎间盘及纤维环组织未见明显破坏。术后3d、8周及12周的Micro-CT三维重建均显示骨水泥在兔椎体松质骨内分布,新生骨组织包裹植入材料,无渗漏,无椎管及椎体前壁破损等并发症。结论：在兔腰椎解剖基础上,以脊椎乳突和副突为骨性标志,可以成功建立一种安全可靠的兔椎体成形术用穿刺模型。     

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.     

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.     

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.     

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.     

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.     

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.