缺血预处理对幼兔心肌保护作用及其机制探讨

目的观察缺血预处理(IPC)是否能保护接受全心离体缺血再灌注的未成熟兔心脏,并探讨ATP敏感性钾通道在IPC中的作用.方法利用Langendorff模型灌注幼兔(14～21d)离体心脏,经历5min缺血、10min再灌的IPC后,用4℃的st.ThomasII停搏液使心脏停跳,观察其在生理体温(39℃)下接受45min缺血、40min再灌的血液动力学、冠脉流出液心肌酶及心肌能量变化.并利用ATP敏感性钾通道阻断剂aibenclamide(Gli)作为工具药来研究IPC保护作用的机制.结果IPC明显改善心率(HR)、冠脉流出量(CF)、心脏功能指标(LVDP、±dp/dtmax)恢复率,减少室性心律失常,保存心肌ATP含量;肌酸磷酸激酶同工酶(CK-MB)漏出减少.预处理前灌注Gli(10μμmol/L)20min则完全消除了上述IPC的保护效应.结论IPC对经历全心缺血再灌注的未成熟兔心肌具有保护作用.这种保护效应可能涉及到ATP敏感性钾通道的开放.     

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。     

不同预处理中线粒体KATP通道开放对未成熟心肌的作用

目的　了解线粒体ATP敏感性钾通道 (mKATP)开放在不同预处理过程中对幼兔心脏的影响 ,并探讨其机制。方法　幼兔 (小于 2 8d) 34只随机分成 5组 ,对照组 (n =8) :平衡 30min后缺血再灌注 ;二氮嗪预处理组 (n =8) :缺血前二氮嗪 ( 10 0 μmol/L)灌注 5min后重碳酸盐缓冲液 (KH液 )冲洗 10min ,St.ThomasⅡ (STH)停跳 ;二氮嗪 + 5 羟葵酸 ( 5 HD)预处理组 (n =5 ) :二氮嗪 ( 10 0 μmol/L)和 5 HD( 10 0 μmol/L)一起灌注 5min ;缺血预处理 (IPC)组 ( n =8) :平衡 15min后全心缺血 5min ,复灌 10min行IPC ,STH停跳 ;IPC + 5 HD组 (n =5 ) :IPC前用 5 HD ( 10 0μmol/L)灌注 5min。采用LangendOrff模型 ,常温 ( 38℃ )缺血 30min ,复灌 45min。 结果　缺血 /再灌注 (I/R)后二氮嗪组的线粒体评分较IPC组 (P <0 .0 5 )和对照组 (P <0 .0 1)低 ,IPC前给予 5 HD后线粒体评分仍较对照组低 (P <0 .0 5 )。二氮嗪组和IPC组左室发展压力 (LVDP)、左室压力上升和下降最大速率 (±dp/dtmax)恢复在多个时间点上均优于对照组 ,心肌组织ATP含量高于对照组 (P <0 .0 1) ,心肌酶较对照组降低 (P <0 .0 1)。结论　二氮嗪预处理能产生与IPC相似的心肌保护作用 ,并且对线粒体的保护效果较IPC好。mKATP通道和细胞膜KATP     

一氧化氮在异丙酚减轻大鼠离体心脏缺血再灌注损伤中的作用

目的 探讨一氧化氮在异丙酚减轻大鼠离体心脏缺血再灌注损伤中的作用.方法 成年雄性SD大鼠,体重220～330 g,采用Langendorff装置建立大鼠离体心脏灌注模型,选取符合实验标准的心脏模型18个,随机分为3组(n=6):K-H液灌注组(A组)、异丙酚灌注组(B组)和异丙酚+L-NAME灌注组(C组).各组用相应的K-H液灌注15 min,常温全心停灌20 min,然后用相应的K-H液复灌60 min.采用电化学微传感器法测定心肌一氧化氮(NO)含量,免疫组化法测定心肌一氧化氮合酶(NOS)含量,分光光度计测定心肌NOS活性,测定心率、左心室舒张末压、左心室发展压、左心室压变化速率最大值和左心室压变化速率最小值,定时收集右心室流出液以测定冠脉流量.结果 与A组相比,B组和C组复灌后各时点心功能改善(P＜0.05);与C组相比,B组复灌后各时点心功能改善(P＜0.05);B组心肌NO含量和NOS活性较A组升高(P＜0.05),但2组心肌NOS含量差异无统计学意义(P＞0.05).结论 缺血再灌注导致心肌内源性NO的含量降低.异丙酚减轻大鼠离体心脏缺血再灌注损伤可能是通过增加心肌内源性NO生成实现的.     

缺血后处理对大鼠离体心脏缺血再灌注损伤的作用

目的探讨缺血后处理对大鼠离体心脏缺血再灌注损伤的作用。方法24只Wistar大鼠,随机分为3组(n=8):正常对照组(C组)、缺血再灌注组(I/R组)、缺血后处理组(IPC组)。采用大鼠离体心脏Langendorff灌流模型,C组用K-H液灌注160min;I/R组全心缺血40 min,再灌注120 min; IPC组全心缺血40 min后,再灌注10 s,缺血10 s,反复6次,然后持续再灌注118 min。测定再灌注15、30、120 min时冠脉流量(CF)及冠脉流出液心肌肌钙蛋白I(cTnI)浓度,再灌注120 min时,取心肌组织,测定丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性,电镜下观察心肌细胞超微结构。结果缺血再灌注可导致CF降低,冠脉流出液cTnI浓度升高,心肌SOD活性下降,MDA含量升高,心肌细胞超微结构产生病理学改变,缺血后处理可减弱上述改变。结论缺血后处理减轻脂质过氧化反应,对大鼠离体缺血再灌注心脏产生保护作用。     

缺血预处理对兔离体心脏长期保存的心肌保护作用

目的　观察缺血预处理对离体心脏长期保存的心肌保护作用。方法　将 2 4只家兔随机分为 4组 ,每组 6只 ,分成空白对照组、预处理组、保存组和预处理后保存组。离体兔心脏用Langendorff装置灌注稳定后 ,分别给予缺血预处理后再灌注、心脏保存 1 8h后再灌注及缺血预处理后再经 1 8h保存后再灌注 60min ,观察左室收缩功能的恢复率、冠脉回流液中碱性磷酸激酶(CK)、乳酸脱氢酶 (LDH)的浓度以及心肌形态结构改变。结果　预处理组同空白对照组相比 ,各项指标差异无显著性 (P >0 .0 5)。单纯保存组同对照组相比 ,左室收缩功能明显减弱 ,冠脉回流液中心肌酶的漏出明显增加 ,光镜及电镜观察心肌损伤严重。而经预处理后再保存组 ,左室收缩功能的恢复率较单纯保存组有明显提高 [(51 .9± 7.5) %比 (36 .6± 4 .9) % ,P <0 .0 5] ,心肌酶漏出明显减少 [CK :(31 2± 52 )IU/L比 (642± 1 0 8)IU/L ;LDH :(2 9± 9)IU/L比 (76± 1 0 )IU/L ,P <0 .0 5] ,光镜及电镜观察 ,心肌损伤程度明显减轻。结论　缺血预处理过程本身对心肌细胞无明显损伤 ,是比较安全的 ;缺血预处理对离体心脏长期保存有明显的保护作用     

二氮嗪预处理对未成熟兔心脏的保护作用

目的 了解二氮嗪预处理对未成熟兔心脏有无保护作用,并探讨其机制。方法 大耳白幼兔(小于28 d)21只随机分成三组:对照组(Ⅰ组n=8):K-H缓冲液灌注30 min后St.ThomasⅡ号停跳液(STH)停跳;二氮嗪预处理组(Ⅱ组n=8):二氮嗪(100μmol/L)灌注5 min,再K-H液灌注10min后STH停跳;二氮嗪+5-HD组(Ⅲ组n=5):二氮嗪和5-HD(均100μmol/L)共同灌注5 min后停跳。在LangendOrff模型上进行离体心脏常温缺血/再灌注(I/R)实验。观察再灌后血液动力学恢复、冠脉流出液心肌酶、心肌组织内ATP含量及心肌超微结构变化。结果 再灌后Ⅱ组左室发展压(LVDP)、左室压力上升和下降最大速率(±dp/dtmax)的恢复率在多个时间点上均高于Ⅰ组,再灌末心肌组织ATP含量也高于Ⅰ组(P<0.01),冠脉流出液中的三种心肌酶值均较Ⅰ组降低(P<0.01)。Ⅱ组的线粒体评分低于Ⅰ组(P<0.01),Ⅲ组线粒体评分回到Ⅰ组水平(P>0.05)。结论 二氮嗪能通过开放线粒体ATP敏感性通道而发挥对幼兔心肌的保护作用。     

沉默信息调节因子1在缺血预处理减轻大鼠心肌缺血再灌注损伤中的作用

目的 探讨沉默信息调节因子1(SIRT1)在缺血预处理减轻大鼠心肌缺血再灌注损伤中的作用.方法 雄性SD大鼠48只,体重200 ～ 250 g,12周龄,采用随机数字表法,将其分为4组(n=12):假手术组(S组)、缺血再灌注组(I/R组)、缺血预处理组(IPC组)和缺血预处理+SIRT1抑制剂组(IPC+ ex527组).采用结扎左冠状动脉前降支30 min再灌注120 min的方法制备心肌缺血再灌注损伤模型,IPC组和IPC+ ex527组进行缺血预处理(缺血5 min,再灌注5 min,重复3个循环,共30 min),IPC+ ex527组分别于缺血前15 min及再灌注前1 min静脉注射ex527 1 μg/kg.分别于缺血前和再灌注120 min时采集股动脉血样,测定血清TNF-α和IL-6的浓度,处死大鼠,取心肌组织,测定乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)活性、SIRT1表达和NF-κB p65乙酰化水平.结果 与S组比较,I/R组和IPC+ ex527组再灌注120 min时血清TNF-α、IL-6浓度、心肌组织LDH、CK-MB活性和NF-κB p65乙酰化水平升高,心肌组织SIRT1表达下调(P＜0.05);与I/R组比较,IPC组血清TNF-α、IL-6浓度、心肌组织LDH、CK-MB活性、NF-κB p65乙酰化水平降低,心肌组织SIRT1表达上调(P＜0.05),IPC+ ex527组上述指标差异无统计学意义(P＞0.05);与IPC组比较,IPC+ ex527组血清TNF-α、IL-6浓度、心肌组织LDH、CK-MB活性、NF-κB p65乙酰化水平升高,心肌组织SIRT1表达下调(P＜0.05).结论 SIRT1参与了缺血预处理减轻大鼠心肌缺血再灌注损伤.     

11,12-环氧二十碳三烯酸预处理对未成熟兔离体心脏的影响

目的　观察 11,12 环氧二十碳三烯酸 ( 11,12 EET)预处理对离体未成熟兔心肌缺血再灌注的保护作用 ,并探讨其可能机制及意义。方法　利用Langendorff灌注装置 ,建立心肌缺血再灌注模型。 2 4只未成熟兔随机分成对照组、缺血预处理组 (IPC组 )、11,12 EET预处理组 (EET组 ) ,观察常温缺血 ( 3 7℃ ) 2h再灌注 1h前后心功能变化 (左室变化压、左室舒张末期压、心室最大压力变化速率、冠状动脉流量等指标 )、心肌含水量、心律失常评分、心肌酶学 [肌酸激酶 (CK )、乳酸脱氢酶 (LDH ) ]指标。结果　IPC组及EET组心功能恢复、心律失常发生及心肌酶学指标均优于对照组 ;与IPC组相比 ,EET组的心肌含水量 ( 75 .3± 3 .5 ) %、CK( 117.4± 8.3 )IU/L、LDH ( 5 2 .7±13 .4)IU/L均较低 (P <0 .0 5 ) ,冠状动脉流量 ( 12 .7± 1.5 )ml则较大 ,这两组的其余观察指标差异无显著性 (P >0 .0 5 )。结论　 11,12 EET预处理未成熟兔离体心脏能产生优于缺血预处理的心肌保护作用。     

尼可地尔后处理对大鼠心肌缺血再灌注损伤的影响

目的 探讨尼可地尔后处理和缺血后处理对大鼠心肌缺血再灌注损伤的影响。方法 健康成年SD大鼠24只,建立Langendorff模型灌注离体心脏,随机分为3组,每组8只,对照组（IR组）：全心缺血40min,再灌注Krebs-Henseleit缓冲液（K-H液）60min;缺血后处理组（IPC组）：全心缺血40min,再灌注10s、缺血10s,反复6次后,再灌注K-H液58min;尼可地尔后处理组（NPC组）：全心缺血40min,灌注含20μmol/L尼可地尔的K-H液10min,然后再灌注K-H液50min。测定缺血前5min、再灌注30min及结束时冠脉流出液中碱性磷酸激酶同工酶（CK-MB）活性,再灌注结束即刻取左心室组织,测定超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量、ATP含量,电镜观察心肌超微结构。结果 与IR组比较,IPC组和NPC组再灌注期CK-MB活性及MDA含量降低,SOD活性和ATP含量增高（P＜0．05）,IPC组和NPC组上述指标比较差异无统计学意义（P＞0．05）。IPC组和NPC组的心肌超微结构损伤程度轻。结论 尼可地尔后处理和缺血后处理均可以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的生成、增强心肌抗氧化能力和减少细胞能量消耗有关。     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.