透明质酸对创面胶原代谢的影响

目的:通过观察外源性透明质酸(HA)对兔耳创面胶原代谢的影响,探讨外源性透明质酸在伤口愈合中的作用.方法:18只日本大耳白兔,建立兔耳创伤愈合模型后,随机分成2％HA治疗组(A组),1％HA治疗组(B组)和生理盐水对照组(C组).观察创面愈合及瘢痕形成情况,术后第3、7、10、14、18天取标本匀浆后测定羟脯氨酸(HPr)含量,将数据进行统计学处理.结果:A、B两组羟脯氨酸含量明显低于C组(P＜0.01),A、B两组间也有统计学差异(P＜0.05).A、B两组创面愈合相对C组延迟,形成瘢痕小于C组.结论:外源性HA能够抑制成纤维细胞合成胶原,延迟创面愈合,减少瘢痕形成,其作用有剂量依赖性.     

外源性透明质酸对创面纤维黏连蛋白表达的影响

目的探讨外源性透明质酸延迟创面愈合的作用机理.方法成年日本大耳白兔18只,建立兔耳皮肤创伤愈合模型,随机分2%透明质酸治疗组(A组)、1%透明质酸治疗组(B组)和磷酸盐缓冲液对照组(C组).观察大体形态、组织学变化及平均愈合时间,未愈合创面面积及纤维黏连蛋白的表达情况.结果①三组平均愈合时间为(11.7±0.6)天,(11.3±0.6)天,(10.8±1.0)天,三组之间有显著差异(P＜0.05).A、B组与C组比较各时间点未愈合面积也有显著差异(P＜0.05).②组织学观察,A、B组胶原纤维较细、排列整齐.C组胶原纤维较粗大、排列紊乱.③纤维黏连蛋白的表达,A、B组纤维黏连蛋白的表达少于C组(P＜0.01).结论①外源性透明质酸抑制创面纤维黏连蛋白的表达是延迟创面愈合的原因之一.②透明质酸的这一作用与其浓度有依赖关系.     

外源性透明质酸对兔耳创面胶原代谢的影响

目的　通过观察外源性透明质酸(HA)对兔耳创面愈合前后胶原代谢的影响,探讨透明质酸抑制瘢痕增生的机理。方法　18只日本大耳白兔,建立兔耳创伤愈合模型后,随机分成2％HA治疗组（A组）,1％HA治疗组（B组）和生理盐水对照组（C组）。术后第3、7、10、14、18天取标本匀浆后测定羟脯氨酸（HPr）含量,将数据进行统计学处理。结果　A、B两组羟脯氨酸含量明显低于C组（P＜0.01）,A、B两组间也有统计学差异（P＜0.05）。结论　HA能够抑制成纤维细胞合成胶原,其作用有剂量依赖性。     

外源性透明质酸对兔耳创面胶原代谢的影响

目的　通过观察外源性透明质酸 (HA)对兔耳创面愈合前后胶原代谢的影响 ,探讨透明质酸抑制瘢痕增生的机理。方法　 18只日本大耳白兔 ,建立兔耳创伤愈合模型后 ,随机分成 2 %HA治疗组 (A组 ) ,1%HA治疗组 (B组 )和生理盐水对照组 (C组 )。术后第 3、7、10、14、18天取标本匀浆后测定羟脯氨酸 (HPr)含量 ,将数据进行统计学处理。结果　A、B两组羟脯氨酸含量明显低于C组 (P <0 .0 1) ,A、B两组间也有统计学差异 (P <0 .0 5 )。结论　HA能够抑制成纤维细胞合成胶原 ,其作用有剂量依赖性     

外源性透明质酸对创面纤维黏连蛋白表达的影响

目的　探讨外源性透明质酸延迟创面愈合的作用机理。方法　成年日本大耳白兔 18只 ,建立兔耳皮肤创伤愈合模型 ,随机分 2 %透明质酸治疗组 (A组 )、1%透明质酸治疗组 (B组 )和磷酸盐缓冲液对照组 (C组 )。观察大体形态、组织学变化及平均愈合时间 ,未愈合创面面积及纤维黏连蛋白的表达情况。结果　①三组平均愈合时间为 (11.7± 0 .6 )天 ,(11.3± 0 .6 )天 ,(10 .8± 1.0 )天 ,三组之间有显著差异 (P <0 .0 5 )。A、B组与C组比较各时间点未愈合面积也有显著差异 (P <0 .0 5 )。②组织学观察 ,A、B组胶原纤维较细、排列整齐。C组胶原纤维较粗大、排列紊乱。③纤维黏连蛋白的表达 ,A、B组纤维黏连蛋白的表达少于C组 (P <0 .0 1)。结论　①外源性透明质酸抑制创面纤维黏连蛋白的表达是延迟创面愈合的原因之一。②透明质酸的这一作用与其浓度有依赖关系。     

透明质酸对创面愈合胶原代谢影响的实验研究

目的　探讨外源性透明质酸 (HA)抑制瘢痕形成的作用机理及其浓度依赖性关系。方法　健康成年大鼠 4 5只 ,复制背部创伤模型 ,随机分成 2 %HA治疗组 (A组 )、1%HA治疗组 (B组 )、磷酸盐缓冲液 (PBS)对照组 (C组 ) ,观察大体形态和组织学改变 ,平均愈合时间和残留面积的大小 ,测定愈合部位组织蛋白、羟脯氨酸 (HPr)、Ⅲ型前胶原 (PCⅢ )的含量。结果　① 3组的平均愈合时间为 ( 15 2± 2 0 ) ,( 14 2± 1 6)和 ( 13 4± 1 4 )d ,A、B两组与C组比较差异有显著性意义 (P <0 0 5 )。A、B两组的残留面积与C组比较差异有显著性意义 ,3组间比较差异也有显著性意义 (P <0 0 5 )。②组织学上 ,A、B两组成纤维细胞增生明显 ,胶原纤维直径较为纤细、排列整齐。C组则显示出明显的炎性细胞浸润 ,新生血管数目增多。③HPr和PCⅢ含量的测定 :A、B两组HPr含量的均值低于C组 (P <0 0 1) ,而PCⅢ的含量却高于C组 (P <0 0 1)。结论　①HA通过对细胞的调控作用 ,可有效地抑制胶原的合成 ,提高Ⅲ型胶原含量 ,使得创面愈合过程中瘢痕形成减少。②HA在创面愈合中抑制瘢痕形成的生物学作用与其浓度成正比关系。     

外源性透明质酸对创面愈合影响的研究

目的　探讨透明质酸 (HA)延迟创面愈合的作用。方法　成年日本大耳白兔 18只 ,建立兔耳创伤愈合模型 ,随机分成 2 % HA治疗组 (A组 ) ,1% HA治疗组 (B组 ) ,磷酸盐缓冲液 (PBS)对照组 (C组 ) ,进行大体形态、组织学变化、平均愈合时间、创面收缩情况、残余创面面积、成纤维细胞 α-平滑肌肌动蛋白表达及超微结构 ,观察 12天。结果　 1三组创面平均愈合时间为 (11.7± 0 .6 )、(11.3± 0 .6 )和 (10 .8± 1.0 )天 ,三组之间有显著差异 (P<0 .0 5 ) ;A、B组与C组比较创面收缩速率及残余面积也有统计学意义 (P<0 .0 5 )。 2组织学见 A、B两组胶原纤维较细 ,排列整齐 ;C组胶原纤维较粗大 ,排列紊乱。 3A、B组 α-平滑肌肌动蛋白的表达少于 C组 ,有统计学意义 (P<0 .0 1)。结论　 HA通过抑制成纤维细胞向肌成纤维细胞转化而抑制创面收缩 ,是延迟创面愈合的原因之一 ;且这一作用与其浓度有依赖关系。     

皮肤源祖细胞-透明质酸复合物对糖尿病大鼠创面愈合的影响

目的研究皮肤源祖细胞（SKP）-透明质酸（HA）复合物的构建方法，观察其对糖尿病（DM）大鼠创面愈合的影响。方法分离培养SD大鼠SKP，以HA为载体构建复合物，观察复合物中SKP的分化特性。选取60只SD大鼠腹腔注射链脲菌素诱导成DM模型．背部对称制作2个直径1cm全层皮肤缺损创面，随机分为SKP-HA组，创面涂布100μl SKP-HA；HA组，创面涂布100μl HA；对照组，创面涂布DMEM／F12培养基。每组20只。各组大鼠于伤后1、2、3、4周检测创面愈合率，留取创面组织标本检测羟脯氨酸（Hyp）含量，并观察SKP在创面愈合过程中的迁移。结果大鼠SKP与HA共培养后生长良好，复合物中的SKP可保持其特性：向神经元细胞、神经胶质细胞、脂肪细胞分化。伤后2周SKP-HA组、HA组的创面愈合率分别为（72．1±2．8）％、（53．7±2．9）％，均明显高于对照组的（42．5±1．5）％（P＜0．05）；伤后3周SKP—HA组高于HA组及对照组（P＜0．05或0．01）；伤后4周SKP—HA组、HA组创面完全愈合，与对照组比较，差异有统计学意义（P＜0．01）。伤后1周各组Hyp含量差异无统计学意义（P＞0．05）；伤后2～4周，SKP-HA组、HA组Hyp含量均高于对照组（P＜0．01）；伤后3、4周SKP-HA组高于HA组（P＜0．01）。SKP在创面得以成活并随时间的延长逐渐向真皮层迁移。结论SKP-HA复合物可促进DM大鼠创面愈合。     

外源性透明质酸对创面愈合组织的影响

目的：研究外源性透明质酸对创面愈合组织中生化组分的影响，以期探索外源性HA在创伤愈合中的作用及其机制。方法：在小型猪背部的去中厚皮创面上应用不同浓度和剂型的外源性HA，并于术后第3、7、14、21、28天切取创面组织及正常皮肤，测定其糖胺多糖、HA及Ⅲ型胶原的含量变化。结果：愈合过程中，实验组创面愈合组织中的GAG、HA含量逐渐升高，1周时达峰值并能维持3周；创面对照组术后3天也见增高，但随后即迅速下降。实验组的Ⅲ型胶原含量也始终明显高于对照组，其中又以1．0％、2．0％HA组最高。结论：外源性HA能显著增高愈合组织中HA、Ⅲ型胶原含量并能维持较长时间，从而有利于创伤愈合及减轻瘢痕形成。     

透明质酸钠预防面颈部外伤及手术后瘢痕50例

目的:观察外源性透明质酸钠抑制创口瘢痕形成的临床效果.方法:外伤及手术后的患者100例,随机分成两组,实验组用1.7%的透明质酸钠创口局部定期注射,对照组作空白对照.观察创口术后的缝线反应,计算创口愈合后不同时期同等长度瘢痕的面积.结果:术后1周两组缝线反应有显著性差异(P＜0.05).两组瘢痕面积在术后1、3、6个月时比较有显著性差异(P＜0.05).结论:创口局部注射外源性透明质酸钠能有效抑制创面瘢痕形成.     

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.     

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.     

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.