不同剂量维生素K_3对大鼠肾骨桥蛋白表达的影响

目的探讨不同剂量的维生素K3对大鼠肾骨桥蛋白(osteopontin,OPN)表达分布的影响。方法对饮用相同诱石剂的50只大鼠分6组分别给予4.0、3.0、2.0、0.8mg/d和0.4mg/d剂量的维生素K3,观察肾OPN表达分布变化。结果正常饮食鼠肾OPN表达部位集中在远曲小管,应用诱石剂后OPN表达部位扩展到近曲小管,维生素K3能够减少OPN表达量,随着维生素K3剂量由0.4mg/d增加到4mg/d,肾脏OPN表达量从(70±22)%逐渐减少到(20±8)%。结论维生素K3可减少诱石剂导致的肾曲小管OPN表达分布的变化。     

维生素D和维生素K对大鼠结石模型尿晶体成分的影响

目的进一步明确维生素D和维生素K与肾结石的关系,探讨成石机制。方法将健康成年雄性SD大鼠24只随机分成4组,即对照组、诱石组、维生素D组和维生素K组,收集第1、3、7天约24小时尿,测定尿晶体成分的浓度。结果维生素D组尿钙和草酸明显高于对照组和诱石组,尿镁和柠檬酸显著降低（P＜0．05）。维生素K组尿草酸明显低于诱石组（P＜0．05）。结论维生素D可能通过多种机制促进肾结石形成,而维生素K有抑制结石形成的作用。     

表达甲酰辅酶A转移酶的大肠杆菌对大鼠尿草酸浓度的影响

目的探讨喂饲表达甲酰辅酶A转移酶（FCoAT）的大肠杆菌Nissle1917（EcN-Frc）对大鼠尿草酸浓度的影响。 方法将30只雄性SD大鼠随机分为六组（编号A-F）,每组5只。除A组外,其余五组在食物中每克添加1%草酸。B组每次喂食前30 min,喂食1 ml EcN-Frc培养液,C、D、E、F组喂食1 ml EcN-Frc悬液（活细菌数10³）。C、D、E、F组喂饲细菌的方式分别为每日1次,每3 d一次,每周一次和观察期内首日喂养一次。实验周期为2周,分别于喂养当日,喂养后3、6、9、14 d分别记录大鼠健康情况和24 h尿草酸排泄量。 结果口服ECN-Frc能有效减低高草酸饮食大鼠的24 h尿草酸排泄量。含10³活菌数的EcN-Frc在喂养后3 d即可发挥作用。1次喂服10³个活菌数的ECN-Frc,2周后仍能有效降低大鼠尿中草酸浓度。所有大鼠观察期内均体健,未见明显异常。 结论低剂量口服EcN-Frc能有效降低高草酸饮食大鼠的24 h尿草酸排泄量,且安全,耐受性好。     

钙拮抗剂抑制大鼠肾草酸钙结石生成的实验研究

目的观察不同剂量硝苯地平灌喂对大鼠肾草酸钙结石生成的影响。方法选用60只雄性SD大鼠,体重200~250g,随机分为6组,分别为空白对照组、单纯硝苯地平组、单纯诱石组、诱石 3、6、10mg·kg-1·d-1硝苯地平干预组,每组各10只。应用乙二醇诱导大鼠产生肾草酸钙结石,4周后观察大鼠肾小管结晶沉积情况、肾组织自由基水平、细胞凋亡情况和大鼠血和尿多项生化指标的变化。结果与单纯诱石组相比,各硝苯地平干预组的肾小管草酸钙结晶评分分别降低37.0%、55.6%、66.7%(P均<0.05),肾小管上皮细胞凋亡数分别减少30.2%、44.6%、48.7%(P均<0.05),两者有显著相关性(r=0.8251);肾组织中MDA含量也分别减少14.5%、20.4%、21.8%,而SOD活性增加3.5%、8.7%、12.6%(P均<0.05);量效关系呈正相关。结论硝苯地平通过减少高尿草酸所致的肾小管上皮细胞凋亡,能有效抑制饮用诱石剂大鼠的肾小管结石生成。     

维生素D3和维生素K3对实验性肾结石的影响

目的：探讨维生素C3和维生素K3与尿石症的关系。方法SD大鼠36只,随机分为对照组（A组）、成石组（B组）、维生D3组（C组）、成石＋维生素D3组（D组）、维生素K3组（E组）和成石＋维生素K3组（F组）,用免疫组化和原位杂交技术检测各组大鼠肾脏骨桥蛋白（OPN）及其mRNA的表达量,并测定尿晶体成分的浓度。结果：免疫组化结果显示,OPN主要表达于肾脏远曲小管和集合管,B、C、E组鼠肾和OPN的表达强度明显高于A组（P均＜0．05）;D、F组OPN的表达强度明显高于C、E组（P均＜0．05）,即维生素D3或维生素K3与诱石剂合用时呈相加效应。应用诱石剂后,D组尿钙排泄量明显增加,而F组草酸盐明显低于B组（P＜0．05）。维生素K3可减少尿划石剂后,D组尿排泄量明显增加,而组草酸盐明显低于B组（P＜0．05）。维生素K3可减少尿草酸盐的分泌和草酸钙晶体的沉积。结论：维生素D3可能通过多种机制种促进肾结石殂成,而维生素K3有抑制结石形成的作用。     

维生素D_3和维生素K_3对实验性肾结石的影响

目的　探讨维生素D3 和维生素K3 与尿石症的关系。　方法　SD大鼠 36只 ,随机分为对照组 (A组 )、成石组 (B组 )、维生素D3 组 (C组 )、成石 维生素D3 组 (D组 )、维生素K3 组 (E组 )和成石 维生素K3 组 (F组 ) ,用免疫组化和原位杂交技术检测各组大鼠肾脏骨桥蛋白 (OPN)及其mRNA的表达量 ,并测定尿晶体成分的浓度。　结果　免疫组化结果显示 ,OPN主要表达于肾脏远曲小管和集合管 ,B、C、E组鼠肾OPN的表达强度明显高于A组 (P均 <0 .0 5 ) ;D、F组OPN的表达强度明显高于C、E组 (P均 <0 .0 5 ) ,即维生素D3 或维生素K3 与诱石剂合用时呈相加效应。应用诱石剂后 ,D组尿钙排泄量明显增加 ,而F组草酸盐明显低于B组 (P <0 .0 5 )。维生素K3 可减少尿草酸盐的分泌和草酸钙晶体的沉积。　结论　维生素D3 可能通过多种机制促进肾结石形成 ,而维生素K3 有抑制结石形成的作用。     

苄丙酮香豆素对实验性大鼠肾草酸钙结石形成的影响

目的：探讨Vit．K拮抗剂苄丙酮香豆素(商品名华法令)对大鼠肾草酸钙结石形成的影响。方法：采用乙二醇饮水和氯化铵灌胃作成石剂，30只Wistar大鼠随机分为对照组(A组)、成石组(B组)、华法令组(C组)。饲养4周后，检测大鼠肾组织钙含量和草酸钙晶体形成、24h尿钙、尿草酸含量及血生化指标。结果：成石组和华法令组肾组织中钙、镁含量，24h尿草酸及尿钙、镁排泄量差异无显著性意义；镜下观察发现：华法令组大鼠肾脏草酸钙结晶形成多于成石组，但组间比较差异无显著性意义。结论：苄丙酮香豆素对大鼠肾草酸钙结石的形成无显著影响。     

西梅汁预防大鼠草酸钙肾结石的实验研究

目的 研究西梅汁对乙二醇诱导的大鼠草酸钙肾结石形成的影响及其量效关系.方法 40只wistar大鼠随机分为8组:A空白对照组、B单纯乙二醇诱石组、C～E为西梅汁干预组[分别灌喂西梅汁2、4、8 mL· (kg·d)-1],每组8只.除空白对照组外,余皆用含1％乙二醇去离子水作为大鼠的唯一饮用水源并自由饮用,以诱导生成草酸钙肾结石.分别于实验前日和实验第4周末,检测大鼠尿钙、镁、草酸及枸橼酸浓度;血钙、镁、肌酐和尿素氮浓度;肾脏组织丙二醛(MDA)含量及总超氧化物歧化酶(T-SOD)活性;偏光显微镜观察HE染色肾脏组织草酸钙结晶形成情况;TUNEL法检测肾小管上皮细胞凋亡,以此分析西梅汁及西梅干预防肾结石的量效关系.结果 所用三种剂量的西梅汁均能明显减轻乙二醇所致的各项血尿生化指标和肾小管上皮细胞凋亡指数的改变,大幅增加尿镁浓度,明显减少乙二醇诱导的大鼠草酸钙肾结石的生成,且效果呈剂量依赖性.结论 所用的三种剂量的西梅汁均可明显干预乙二醇诱导的大鼠草酸钙肾结石的生成,且呈正相关的量效关系.     

西梅干预防大鼠草酸钙肾结石的实验研究

目的研究西梅干对乙二醇诱导的大鼠草酸钙肾结石形成的影响及其量效关系。方法 40只Wistar大鼠分为5组:A组空白对照组、B组为单纯乙二醇诱石组、C~E组为西梅干干预组[分别灌喂西梅干匀浆2、4、8mL/(kg·d)],每组8只。除A组外,余皆用含1%乙二醇去离子水于大鼠自由饮用。于实验前日和实验第4周末,分别检测大鼠尿钙、镁、草酸及枸橼酸浓度;血钙、镁、肌酐和尿素氮浓度;肾脏组织丙二醛(MDA)含量及总超氧化物歧化酶(T-SOD)活性;偏光显微镜观察HE染色肾脏组织草酸钙结晶形成情况;TUNEL法检测肾小管上皮细胞凋亡。结果三种剂量的西梅干均能明显减轻乙二醇所致的各项血尿生化指标和肾小管上皮细胞凋亡指数的改变,大幅增加尿镁浓度,明显减少乙二醇诱导的草酸钙肾结石的生成。结论三种剂量的西梅干均可明显干预乙二醇诱导的大鼠草酸钙肾结石的生成,且呈正相关的量效关系。     

青藤碱对阿霉素肾病大鼠PI3K/mTOR信号通路及系膜增生的影响

目的探讨青藤碱对阿霉素肾病大鼠肾组织中磷脂酰-3激酶(phosphatidyl-3 kinase, PI3K)/雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR)信号通路及系膜增生的影响,探究其保护作用机制。方法选用SD大鼠50只,随机取10只经尾静脉注射生理盐水作为正常(Control)组,其余40只大鼠经尾静脉注射阿霉素5 mg/kg,共注射7 d,制备肾病综合征(nephrotic syndrome, NS)模型,造模成功后,随机分为模型组(NS组)、青藤碱低剂量组(25 mg/kg)、青藤碱中剂量组(50 mg/kg)、青藤碱高剂量组(100 mg/kg),每组10只。Control组、NS组经腹腔给予生理盐水,青藤碱各剂量组经腹腔给予相应剂量药物1次/d,共给药28 d。末次给药24 h后,收集各组大鼠血液、尿液后处死大鼠,并取肾组织标本,检测各组大鼠血肌酐(serum creatinine, Scr)、尿素氮(urea nitrogen, BUN)、24 h尿蛋白定量;采用HE染色观察各组大鼠肾脏病理形态变化并计算系膜基质指数;采用透射电镜观察各组大鼠肾小球基底膜增厚情况;采用蛋白免疫印迹法检测各组大鼠肾组织p-PI3K/PI3K、p-mTOR/mTOR、纤维连接蛋白(fibronectin, FN)和Ⅳ型胶原蛋白(type IV collagen, COL4)蛋白表达情况。结果与Control组相比,NS组大鼠肾小球系膜基质增加、肾小管管腔扩张等病理损伤现象及肾小球基底膜增厚严重,且NS组大鼠系膜基质指数、Scr、BUN、24 h尿蛋白定量和肾组织p-PI3K、p-mTOR、FN、COL4蛋白表达量明显升高(P0.05)。与NS组相比,青藤碱高、中、低剂量组大鼠肾小球基底膜增厚等病理损伤缓解,系膜基质指数、Scr、BUN、24 h尿蛋白定量和肾组织p-PI3K、p-mTOR、FN、COL4蛋白表达明显降低(P0.05)。与青藤碱低剂量组比较,青藤碱中、高剂量组肾小球基底膜增厚及肾脏病理损伤最轻,系膜基质指数、Scr、BUN、24 h尿蛋白定量和肾组织p-PI3K、p-mTOR、FN、COL4蛋白表达明显降低(P0.05)。结论青藤碱可能通过抑制PI3K/mTOR信号通路激活,减轻肾小球系膜细胞增生,延缓NS进程。     

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.