胸段硬膜外阻滞对兔心肌梗死后左心室间质胶原代谢的影响

目的 胸段硬膜外阻滞(TEB)对兔心肌梗死(MI)后左室间质早期重构的影响.方法 成年健康新西兰兔随机均分为三组.各组均建立TEB治疗模型:心肌梗死组(MI组)及胸段硬膜外治疗组(TEB组)均结扎左冠状动脉(LAD)制备心肌梗死模型;假手术组(S组)和MI组于硬膜外推注生理盐水,TEB组于硬膜外推注0.1%罗哌卡因0.5 mg/kg.每日2次.4周后处死动物,保存左室组织,制备VG染色心肌组织切片观察间质胶原变化,用病理图像分析软件测量间质胶原含量,计算胶原容积分数.提取左室前壁心肌组织总RNA,用RT-PCR法检测心肌组织基质金属蛋白酶-2(MMP-2)mRNA表达水平,用明胶酶谱法检测MMP-2酶比活性.结果 TEB组间质胶原生成较MI组大为减少,胶原容积分数(ICVF)TEB组在非梗死区及梗死灶交界区均较MI组明显降低(P<0.01),其中TEB组非梗死区ICVF与S组比较差异无统计学意义;MMP-2 mRNA表达水平TEB组明显低于MI组(P<0.01),TEB组基质金属蛋白酶-2活性形式(AMMP-2)和基质金属蛋白酶-2原形(LMMP-2)比活性较MI组降低(P<0.05).结论 TEB通过影响MI后MMP-2表达及酶活性改变,抑制MI后心肌间质胶原代谢,可能阻止心肌梗死后左心室间质重构.     

平滑肌细胞移植对心肌梗死后早期心肌基质金属蛋白酶2、9和抑制因子3含量的影响

目的评价平滑肌细胞移植对心肌梗死后早期心肌间质重构的影响。方法选用48只雌性Wistar大鼠,采用随机数字表法分成对照组(n=24)和平滑肌细胞移植组(n=24),经左冠状动脉远端结扎后建立心肌梗死动物模型,立即对梗死区边缘行室壁注射含有1×106个平滑肌细胞或不含细胞的磷酸盐缓冲液(PBS)0.5ml。在移植后1周,通过逆转录-聚合酶链反应(RT-PCR)和免疫杂交观察大鼠心肌内基质金属蛋白酶2、9(MMP-2、MMP-9)和基质金属蛋白酶抑制因子3(TIMP-3)的信使核糖核酸(mRNA)和蛋白变化。结果植入的平滑肌细胞能够存活;平滑肌细胞移植组大鼠缺血区TIMP-3mRNA(1.06±0.22vs.0.81±0.19,t=-2.358,P=0.033)及其蛋白含量(3.33±0.53vs.1.63±0.47,t=-6.802,P0.001)明显高于对照组;平滑肌细胞移植组大鼠缺血区MMP-2、MMP-9mRNA(0.49±0.12vs.1.16±0.18,t=8.453,P0.001;0.45±0.12vs.0.80±0.11,t=5.884,P0.001)及其蛋白含量(3.98±1.08vs.6.05±0.91,t=4.139,P=0.001;0.39±0.14vs.0.57±0.17,t=2.409,P=0.031)明显低于对照组。结论移植的平滑肌细胞可在心肌梗死区及其周围存活,并且增加梗死后心肌中TIMP-3mRNA和蛋白的含量,降低MMP-2、MMP-9mRNA和蛋白含量,抑制心肌不良重构。     

阿托伐他汀对人胆管癌QBC939细胞系增殖及侵袭的影响

目的 探讨阿托伐他汀(ATV)对人胆管癌QBC939细胞系增殖、侵袭的影响及其可能作用机制方法 应用细胞培养技术培养QBC939细胞,经不同浓度的阿托伐他汀处理后,以MTF法检测阿托伐他汀对QBC939细胞的杀伤抑制率,以Matrigel侵袭实验、迁移实验和半定量RT-PCR检测阿托伐他汀对QBC939细胞的侵袭、运动能力和对细胞内RhoC,MMP-9,p27 mRNA表达的影响情况.结果 阿托伐他汀可明显抑制QBC939细胞的生长及增殖,且其抑制作用呈剂量-时间效应关系:IC50为25 μmoL/L,最强抑制作用时间为48h.Matrigel侵袭实验及迁移实验显示,经10 μmol/L,25 μmol/L,50 μmoL/L药物干预48h后的QBC939细胞,随着浓度的增加,其体外侵袭、运动能力明显减弱(P＜0.05);半定量RT-PCR测定显示,阿托伐他汀作用48h后,QBC939细胞中p27表达含量明显增高、MMP-9的表达降低,而RhoC的表达改变并不明显.结论 阿托伐他汀可抑制人胆管癌QBC939细胞的生长增殖,并减弱其体外侵袭、运动能力.     

成纤维细胞激活基因的调控及改善皮肤老化的研究

目的 通过研究雌二醇、维生素E、维生素C对体外培养的人皮肤成纤维细胞基质金属蛋白酶-1(MMP-1) mRNA、透明质酸合成酶-2(HAS-2) mRNA转录水平的影响,探讨不同药物改善皮肤老化的可能机制.方法 将不同浓度的雌二醇、维生素E、维生素C分别加入体外培养的人皮肤成纤维细胞,逆转录-聚合酶链反应(RT-PCR)检测不同物质对成纤维细胞中HAS-2 mRNA、MMP-1 mRNA表达水平的影响.结果 雌二醇、维生素C对MMP 1 mRNA表达的影响:高剂量组、低剂量组与对照组的差异有统计学意义(P＜0.05),低剂量组与高剂量组差异无统计学意义(P＞0.05).维生素E、维生素C对HAS-2 mRNA表达的影响:高剂量组、低剂量组与对照组的差异有统计学意义(P＜0.05),低剂量组与高剂量组差异无统计学意义(P＞0.05).结论 雌二醇、维生素C可以下调MMP-1基因的转录水平,减少后者对皮肤胶原的降解;维生素E、维生素C可以上调HAS-2基因的转录水平,可能增加透明质酸的合成,从而改善皮肤老化.     

阿托伐他汀对急性冠脉综合征患者血清MMP-9、MMP-2及hs-CRP的影响

目的研究应用阿托伐他汀对急性冠脉综合征患者血清MMP-9、MMP-2及hs-CRP的影响。方法选择ACS患者61例,稳定型心绞痛患者19例及正常对照组30例。随机将ACS患者分为阿托伐他汀组（33例）和常规组（28例）,比较各组间血清MMP-9、MMP-2及hs-CRP的水平变化。结果 ACS组与SA组及正常对照组之间血清MMP-9、MMP-2及hs-CRP水平相比差异有统计学意义,两组干预后血清MMP-9、MMP-2及hs-CRP水平相比差异有统计学意义（P〈0.05）。结论阿托伐他汀可降低ACS患者血清MMP-9、MMP-2及hs-CRP水平,减少冠状动脉粥样斑块基质成分的降解和炎症反应,从而起到稳定动脉粥样硬化斑块的作用。     

阿托伐他汀对急性心肌梗死后1周兔心室肌细胞L-钙离子通道电流的影响

目的通过研究阿托伐他汀预处理对兔急性心肌梗死后1周心室肌细胞L-钙离子通道电流（I Ca-L）的影响,探讨他汀类药物抗心律失常的细胞学离子机制。方法60只新西兰大耳白兔随机分为3组：心梗组、阿托伐他汀治疗组和假手术对照组。采用结扎兔冠状动脉左前降支的方法建立急性心肌梗死动物模型,采用酶解的方法分离心室肌外膜单个心室肌细胞,采用全细胞膜片钳技术,记录跨膜I Ca-L,同时检测各组血脂水平。结果各组动物血脂水平无显著性差异。1周后对照组、心梗组和他汀组I Ca-L电流密度峰值（OmV）分别为（-4．21±1．12）pA／pF（n=20）,（-3．36±0．92）pa／pF（n=20）和（-4．05±0．56）pMpF（n=20）。心梗组较对照组明显下降（P〈0．05）,他汀组较心梗组明显升高（P〈0．05）。另外,心梗组I Ca-L失活曲线较对照组左移,他汀组较心梗组右移。结论急性心肌梗死可导致梗死区心肌细胞I Ca-L明显下降,阿托伐他汀预处理可减轻I Ca-L的异常变化,逆转电重构,而不依赖于降血脂效应,可能为他汀类药物降低心律失常发生率的细胞学离子机制。     

阿托伐他汀与脉血康治疗老年高脂血症临床研究

目的:探讨阿托伐他汀与脉血康治疗老年高脂血症的疗效和不良反应.方法:200例原发性高脂血症患者,随机分为A组阿托伐他汀20mg/d;B组阿托伐他汀10mg/d;C组阿托伐他汀10mg/d+脉血康胶囊2粒/tid,D组阿托伐他汀10mg/d+阿司匹林片0.1/d,每组各50例,治疗8周.观察降脂疗效和不良反应.结果:4组疗效对比,组间比较A组与C组无显著性差异,但分别与B组、D组比较具有统计学意义(P＜0.05).副作用发生率比较,C组比A组副作用更小(P＜0.05)结论:小剂量阿托伐他汀与脉血康能有效降低血脂,副作用小,安全有效.     

阿托伐他汀对系膜增殖性肾炎大鼠肾组织细胞外基质和纤溶酶原激活剂抑制物-1表达的影响

目的：观察阿托伐他汀对系膜增殖性肾炎（MsPGN）大鼠肾组织细胞外基质（ECM）和纤溶酶原激活剂抑制物-1（PAI-1）表达的影响，探讨其肾脏保护作用的机制。方法：采用抗胸腺细胞血清诱发的MsPGN大鼠模型，将SD大鼠随机分为正常对照组、肾炎模型组、小剂量阿托伐他汀治疗组（8mg·kg^-1·d^-1）和大剂量阿托伐他汀治疗组（16mg·kg^-1·d^-1）。治疗12d后。检测各组大鼠血总胆固醇（CHOL）、甘油三酯（TG）、血肌酐（Scr）和24h尿蛋白，以及肾组织Ⅳ型胶原（Col Ⅳ）、纤维结合蛋白（FN）和PAI-1的表达。结果：阿托伐他汀治疗组大鼠24h尿蛋白、肾组织Col Ⅳ、FN和PAI-1 mRNA的表达明显下降。肾组织病理改变明显改善，与模型组相比有统计学差异（P〈0．05），且呈剂量依赖关系。其中肾炎模型组尿蛋白（30．34±0．62）mg／d。阿托伐他汀小剂量治疗组（21．17±0．79）mg／d，大剂量治疗组（9．77±0．54）mg／d。同时，各组血脂水平无明显差异（P〉0．05）。结论：阿托伐他汀可显著改善MsPGN大鼠肾脏病变，抑制肾组织ECM成分和PAI-1的表达。     

miR-21和PDCD4mRNA在大肠癌组织中的表达及其临床意义

目的 探讨miR-21和PDCD4mRNA在大肠癌组织中的表达及与其临床病理特征的关系,并阐明在大肠癌活体组织中miR-21与其靶基因PDCD4表达的关系.方法 用荧光定量PCR技术检测43对大肠癌组织及其对应的正常黏膜组织中的miR-21和PDCD4 mRNA表达量;免疫组化SP法检测PDCD4蛋白的表达.结果 大肠癌组织中miR-21的表达升高(P＜0.05),而PDCD4mRNA的表达降低(P＜0.05).miR-21的表达与大肠癌的淋巴结转移、临床分期(Ⅰ+Ⅱ、Ⅲ+Ⅳ)有关(P＜0.05),而与患者的性别、肿瘤位置、肿瘤大小、浸润深度、远处转移、临床分期(Ⅰ、Ⅱ)无关(P＞0.05);PDCD4mRNA的表达与大肠癌的浸润深度、临床分期(Ⅰ、Ⅱ)有关(P＜0.05),而与患者的性别、肿瘤位置、肿瘤大小、淋巴结转移、远处转移、临床分期(Ⅰ+Ⅱ、Ⅲ+Ⅳ)无关(P＞0.05).miR-21的表达与PDCD4蛋白的核表达、核与浆表达之和存在负相关(P＜0.05),而与PDCD4mRNA、PDCD4蛋白的浆表达无相关性(P＞0.05).结论 miR-21和PDCD4mRNA在大肠癌中的异常表达与大肠癌的预后有关;在大肠癌活体组织中,miR-21通过与PDCD4mRNA的3’非编码区结合抑制PDCD4mRNA翻译成蛋白质.     

阿托伐他汀和辛伐他汀治疗不稳定性心绞痛180例临床分析

目的 比较不稳定性心绞痛患者长期口服阿托伐他汀和辛伐他汀的临床疗效.方法 将180例患者随机分为治疗组和对照组各90例;治疗组口服阿托伐他汀,对照组口服辛伐他汀,分别于治疗后1个月及6个月检测血脂水平以及判断临床疗效.结果 用阿托伐他汀治疗6个月后,能很有效地降低UAP患者血清TC、LDL-C,升高HDL-C,与对照组比较有显著性差异（P ＜0.05）.其缺血相关事件亦有显著性差异（P ＜0.05）.结论 阿托伐他汀治疗不稳定性心绞痛效果显著,值得临床推广.     

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.