蛋白激酶C在未成熟心肌预处理中的作用

目的为进一步加强未成熟心肌保护和临床应用的可行性,探讨蛋白激酶C(PKC)在未成熟心肌预处理保护中的作用。方法建立兔Langendorff灌注模型,将24只幼兔随机分为4组:缺血再灌注组(I/R组)、心脏缺血预处理组(MIP组)、PKC阻滞组(CLT组)和PKC激活剂组(PKC组),观察4组幼兔血流动力学、生化、心肌超微结构等指标。结果 MIP组和PKC组心功能恢复、心肌含水量优于I/R组和CLT组(P0.01),三磷酸腺苷(ATP)含量、超氧化物歧化酶活性、心肌线粒体Ca2+-ATPase活性、心肌线粒体合成ATP的能力优于I/R组和CLT组(P0.01),丙二醛含量、血清肌酸激酶和乳酸脱氢酶漏出率、心肌细胞内Ca2+含量、心肌线粒体Ca2+含量低于I/R组和CLT组(P0.01),心肌超微结构损伤较I/R组和CLT组明显减轻。结论心肌缺血预处理对未成熟心肌具有明显的保护作用,其机制可能是通过PKC的激活起作用。     

参附注射液对心脏直视术中心肌缺血/再灌注损伤的保护作用

目的 探讨参附注射液在体外循环(CPB)心脏直视术中的心肌保护作用.方法 60例择期心脏手术病人随机分成参附组和对照组,每组30例.参附组将2ml/kg的参附注射液加入体外循环预充液中.分别在术前、升主动脉阻断30 min、升主动脉开放再灌注10 min时测定血清磷酸肌酸激酶同工酶(CK-MB)、磷酸肌酸激酶(CK)和乳酸脱氢酶(LOH)含量.测定心肌缺血30 min、缺血再灌注10 min时血浆肌钙蛋白cTnI的浓度.应用透射电镜观察心肌细胞超微结构改变,并对线粒体进行体视学分析.结果 两组病人心肌酶谱、cTnI含量在升主动脉阻断开放后显著升高.缺血30 min时参附组cTnI为(1.19±1.18)mg/ml,对照组cTnI为(2.49±1.68)ng/ml;心肌再寝注10min时参附组cTnI为(4.58±2.22)ng/ml,对照组(9.17±7.43)ng/ml,两组比较,各时点差异均有统计学意义(P＜0.05).超微结构及体视学分析都显示参附注射液能明显减轻心肌细胞、组织结构及线粒体的损伤程度.结论 参附注射液对心肌有一定保护作用,在一定程度上能减轻体外循环期间的心肌缺血,再灌注损伤.     

二氮嗪预处理对大鼠心肌缺血-再灌注损伤的保护作用

目的观察二氮嗪预处理对在体大鼠心肌缺血-再灌注损伤的保护效果,并对其作用机制进行初步的探讨。方法健康SD大鼠14只,采用随机数余数分组法分为两组,对照组和二氮嗪预处理组,每组7只。二氮嗪预处理组按12.5mg/kg的剂量静脉注射二氮嗪溶液,对照组在心肌缺血前静脉注射等量溶媒溶液,结扎冠状动脉前降支致缺血2h,再灌注2h后取心脏,检测缺血心肌组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、心肌梗死面积,观察缺血区凋亡心肌细胞和心肌细胞超微结构的改变。结果二氮嗪预处理组缺血心肌组织MDA含量、心肌梗死区占缺血区的重量百分比和心肌细胞凋亡率明显低于对照组(P<0.05,0.01),心肌超微结构损伤明显轻于对照组。结论二氮嗪预处理对在体大鼠心肌缺血-再灌注损伤具有较好的保护作用。     

参脉注射液对心脏瓣膜置换术的心肌保护作用

目的探讨参脉注射液(SMI)在心脏瓣膜置换术中对心肌缺血-再灌注损伤的保护作用。方法将40例心脏瓣膜置换术患者随机均分为参脉组(SM组)和对照组(C组),SM组在心肺转流(CPB)前静脉给予SMI,C组用等量生理盐水。分别于术前、术中、术后多时点采血,比较两组心肌磷酸激酶(CK)、磷酸激酶同工酶(CK-MB)、肌钙蛋白I(cTnI)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平;记录两组患者的手术时间、主动脉阻断时间及术中、术后各时点血管活性药物的用量,观察主动脉开放后心脏自动复跳率、室性心律失常发生率。结果SM组血清CK、CK-MB、cTnI、MDA等指标均低于C组(P<0.05),而两组SOD活性均降低,但SM组明显高于C组(P<0.05)。SM组室性心律失常发生率、除颤次数及血管活性药物的用量明显低于C组(P<0.01)。结论SMI对心脏瓣膜置换术患者心肌缺血-再灌注损伤具有明显保护作用。     

蛋白激酶C和线粒体ATP敏感性钾通道在未成熟心肌预处理中的作用

目的探讨蛋白激酶C(PKC)和线粒体三磷酸腺苷敏感性钾通道(mitoKATP)在未成熟心肌预处理保护中的作用。方法采用Langendorff离体心脏灌注模型,30只新生日本长耳大白兔分为5组:缺血/再灌注组(I/R组),心脏缺血预处理组(E1组),蛋白激酶C(PKC)阻滞剂chelerythrine(CLT) 心脏缺血预处理(E2组),mitoKATP阻滞剂5-hydroxydecanoate(5-HD) 心脏缺血预处理(E3组),mitoKATP通道开放剂Diazoxide(Diaz)预处理组(E4组)。以血流动力学、生化指标、心肌超微结构等作为观察指标。结果E1和E4组心功能恢复、心肌含水量优于I/R、E2和E4组(P<0.05),三磷酸腺苷含量、超氧化物歧化酶活性、心肌线粒体Ca2 -ATPase活性、心肌线粒体合成三磷酸腺苷(ATP)的能力优于I/R、E2和E4组(P<0.01),丙二醛含量、血清肌酸激酶和乳酸脱氢酶漏出率、心肌细胞内Ca2 含量、心肌线粒体Ca2 含量低于I/R、E2和E4组(P< 0.01),心肌超微结构损伤较I/R、E2和E4组明显减轻。结论心肌缺血预处理对未成熟心肌具有明显的保护作用,其机制可能是通过PKC的激活和mitoKATP通道的开放起作用。     

腺苷含血心脏停搏液在心瓣膜置换术中对心肌的保护作用

目的 研究含血心脏停搏液中加入外源性腺苷在心瓣膜置换术中对心肌的保护作用. 方法 将32例行心瓣膜置换术患者随机分为两组,腺苷组在含血心脏停搏液中加入外源性腺苷,对照组单用含血心脏停搏液,分别经主动脉根部或切开主动脉经冠状动脉窦直接灌注.于术前、主动脉开放后6 h、24 h、72 h采集患者桡动脉血,监测心肌肌酸激酶同工酶(CK-MB)、肌钙蛋白I(cTnI);观察心脏停搏情况,术后机械辅助通气时间及术后正性肌力药物的应用情况;透射电子显微镜观察心肌超微结构的改变. 结果 两组患者均无死亡.腺苷组诱导心脏停搏时间较对照组短(P=0.021);腺苷组的CK-MB水平在主动脉开放后6 h、24 h,cTnI水平在主动脉开放后6 h、24 h、72 h均较对照组低(P<0.05);两组机械辅助通气时间和术后多巴胺使用剂量差异无统计学意义(P>0.05);腺苷组心肌超微结构心肌损伤较对照组明显减轻. 结论 外源性腺苷加入心脏停搏液中能显著提高对心肌的保护效果.     

芬太尼对兔心肌丙二醛和含水量的影响

目的 :研究芬太尼对兔心肌缺血再灌注损伤的保护作用。方法 :建立活体兔心肌缺血再灌注损伤模型。将 18只兔随机分为三组 :对照组、心肌缺血预处理组、芬太尼预处理组。实验结束后测定心肌含水量及丙二醛 (MDA)含量。结果 :与对照组相比 ,两实验组心肌组织含水量及丙二醛含量有明显下降 (P <0 .0 5 )。结论 :芬太尼对兔心肌缺血再灌注损伤具有保护作用。     

烟碱预处理对大鼠心肌缺血-再灌注损伤的保护作用

目的 探讨烟碱预处理对大鼠心肌缺血-再灌注损伤的保护作用及其可能机制.方法 30只健康雄性Sprague-Dawlay大鼠,体重200～250g,随机均分为缺血-再灌组(I-R组)、烟碱预处理组(N组)、假手术组(Sham组).测定三组血浆肌酸激酶同工酶(CK-MB)活性、丙二醛(MDA)含量和超氧化物岐化酶(SOD)活性,心肌组织中髓过氧化物酶(MPO)活性,电镜下观察缺血区心肌超微结构变化.结果 与Sham组比较,I-R组血浆CK-MB活性、MDA含量及心肌组织MPO活性均升高、血浆SOD活性降低(P<0.05或P<0.01);与I-R组比较,N组血浆CK-MB活性、MDA含量及心肌组织MPO活性均降低,血浆SOD活性升高(P<0.05或P<0.01),心肌病理学损伤减轻.结论 烟碱预处理可减轻大鼠心肌缺血-再灌注损伤,其机制可能与减少氧自由基生成、增强心肌抗氧化能力有关.     

心脏直视手术中参附注射液的心肌保护作用

目的观察参附注射液对体外循环下心内直视手术患者心肌损伤标志物的影响。方法30例择期心脏手术患者随机分成参附组和对照组,每组15例。两组麻醉诱导方式相同,参附组在麻醉诱导前静脉输入参附注射液2 ml/kg。分别在术前、心脏再灌注5、10、30、60及120 min测定肌酸磷酸激酶同功酶(LDH)、乳酸脱氢酶(CK-MB)、心肌钙蛋白(cTnI),并进行组间比较。结果两组患者所测心肌损伤标志物在开放升主动脉后显著升高,但参附组明显低于对照组。结论参附注射液能减轻体外循环期间心肌缺血-再灌注损伤,对心肌有一定保护作用。     

黄芪预处理对未成熟兔心肌缺血/再灌注损伤的保护作用

目的 观察黄芪预处理对未成熟兔心肌缺血，再灌注(I/R)损伤的保护作用及其机制。方法 24只幼兔(14—21d)随机分为三组，每组8只，利用Langendorff模型灌注其离体心脏。平稳灌注30min后，向球囊缓慢注入生理盐水，调整左室舒张压(LVDP)为10mmHg。对照组：继续灌注15min；黄芪组：黄芪注射液灌注15min；5-羟葵酸液(5-HD)组：5-HD灌注5min，黄芪注射液灌注10min。三组心脏均经历停灌30min(保温、保湿)、缺血自动停跳及再灌注45min复制全心缺血再灌注(I/R)模型。观察各组的血液动力学、冠脉流出液心肌酶活性及心肌能量变化、病理学和分子生物学的改变。结果 黄芪组左心功能、冠脉流量恢复及再灌后心肌组织内ATP含量明显优于对照组及5-HD组，心肌酶活性明显低于对照组及5-HD组，心肌细胞线粒体超微结构分析显示黄芪组线粒体损伤轻于对照组及5-HD组，心肌诱导型一氧化氮合酶含量高于对照组及5-HD组。结论 黄芪注射液预处理对未成熟兔心肌有一定的保护作用，其机制之一是开放KATP通道。     

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.