缺血预处理对大鼠小体积供肝的保护作用及机制

目的探讨缺血预处理（IPC）对大鼠小体积供肝的保护作用及其机制。方法120只SD大鼠随机分为3组（每组20对）：无热缺血组（NWI）、缺血再灌注组（WI）和缺血预处理组（IPC）。用双袖套法建立大鼠小体积肝移植模型。各组10只受体大鼠于术前1d、术后1、2、3、5d取血，用自动生化分析仪检测AST和ALT。NWI组于供肝灌注前及植入后0．5、1、2、3h，WI组于热缺血前及植入后0．5、1、2、3h，IPC组于IPC前、IPC后及植入后0．5、1、2、3h取肝组织，用硝酸还原法检测其NO浓度。结果IPC可降低大鼠小体积肝移植术后血清AST和ALT浓度，提高再灌注早期肝脏组织NO的浓度，降低再灌注晚期肝脏组织NO的浓度（P〈0．05）。结论NO在大鼠肝脏的缺血再灌注损伤中可能具有双重作用。IPC对大鼠小体积供肝的缺血再灌注损伤有保护作用。其机制可能是通过促进供肝再灌注后早期NO合成，改善肝脏微循环，同时抑制供肝再灌注后晚期NO合成，减轻过量NO的损伤作用，从而保护移植肝脏功能。     

缺血预处理对大鼠肝脏部分切除术后残留肝脏的保护作用及其机制的研究

目的　探讨缺血预处理 (ischemicpreconditioning ,IPC)对大鼠肝脏部分切除术后残留肝脏的保护作用及其机制。方法　 5 0只雄性SD大鼠随机均分为假手术 (Sham)、单纯热缺血 (warmis chemia ,WI)、IPC、IPC L arginine(NO供体 )和WI NAME(NO合成酶抑制剂 ) 5组。术前、术后 1、2、3d检测血清AST和ALT ,术前、IPC后、热缺血后 0 5、1、2、3h检测肝脏组织NO浓度。AST和ALT用自动生化分析仪检测 ,NO用硝酸还原法检测。结果　WI、IPC、IPC L arginine及WI NAME组术后AST和ALT均高于Sham组 (P <0 0 5或P <0 0 1) ,IPC和WI NAME组术后AST和ALT低于WI和IPC L arginine组 (P <0 0 5 )。WI、IPC、IPC L arginine及WI NAME组术后 0 5h肝脏组织NO浓度开始升高(P <0 0 5或P <0 0 1) ,IPC和WI NAME组术后肝脏组织NO浓度低于WI和IPC L arginine组 (P <0 0 5 )。结论　IPC对大鼠肝脏部分切除术后残留肝脏的缺血再灌注损伤有保护作用。IPC通过抑制大鼠热缺血再灌注肝脏产生NO ,减少NO所诱发的肝脏组织细胞的凋亡或坏死 ,保护肝脏功能。     

α-硫辛酸对大鼠肝脏部分热缺血再灌注损伤的保护作用

目的观察α-硫辛酸对大鼠肝脏部分热缺血再灌注损伤的保护作用。方法建立Wistar大鼠肝脏部分热缺血再灌注模型。将大鼠随机分为损伤组（A组）和处理组（B组），缺血前15min从尾静脉分别注射生理盐水和α-硫辛酸，再灌注后1、3、6和12h分别取血和肝脏组织，检测血清丙氨酸氨基转移酶（GPT）、谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GSH-PX），免疫组织化学检测肝脏组织中核转录因子．KBp65（NF-κBp65），RT-PCR法检测肝脏组织中巨噬细胞炎性蛋白．2mRNA（MIP-2mRNA）的表达。结果A组血清GPT和GSH-PX在1、3、6、12h都明显高于B组P〈0．01）；A组血清GSH明显低于B组（P〈0．01）；B组肝脏组织中NF-κBp65和MIP-2mRNA表达明显低于A组（P〈0．01）。结论α-硫辛酸能明显减轻大鼠肝脏缺血再灌注损伤，可能与直接清除氧自由基、增加GSH产生以及减少NF—κB的活化和GSH的消耗有关。     

臭氧氧化预处理在肾缺血再灌注损伤中对内皮型一氧化氮合酶表达的影响

目的 观察臭氧氧化预处理对大鼠急性肾缺血再灌注损伤的保护作用及其对内皮型一氧化氮合酶（eNOS）表达的影响.方法 38只8周龄雄性Wistar大鼠按随机数字表法随机分为4组.（1）假手术组（n＝8）：仅切除右肾;（2）缺血再灌注组（n＝10）：切除右肾、游离左肾后夹闭左肾动、静脉45 min再开通;（3）臭氧氧化预处理组（n＝10）：与缺血再灌注组建模方法一致,但在建模前15 d起每天1次经直肠灌注法吹入氧气和臭氧的混合气体5~5.5 mL;（4）氧气预处理组（n＝10）：与臭氧氧化预处理组建模方法一致,但经直肠仅吹入氧气（13 mg/kg）.建模后24 h检测各组大鼠血清肌酐、血尿素氮和血清一氧化氮浓度;48 h后采用免疫组织化学法和逆转录PCR法检测各组大鼠肾组织eNOS表达;蛋白质印迹法检测肾组织胞浆eNOS含量.结果 建模后24 h,缺血再灌注组大鼠血清肌酐为（117±20）μmol/L,血尿素氮为（32.8±7.6）mmol/L,血清一氧化氮为（58±12）μmol/L,均高于假手术组,差异有统计学意义（均P〈0.05）.臭氧氧化预处理组血清肌酐为（63±16）μmol/L,血尿素氮为（17.4±5.2）mmol/L,低于缺血再灌注组和氧气预处理组,差异有统计学意义（均P〈0.05）;血清一氧化氮为（84±14）μmol/L,均高于缺血再灌注组和氧气预处理组,差异有统计学意义（均P〈0.05）.臭氧氧化预处理组肾组织学Paller评分（41±6）低于缺血再灌注组（62±9）,eNOS灰度值（163±15）高于缺血再灌注组（126±18）,差异有统计学意义（均P〈0.05）.假手术组大鼠肾组织内有微量eNOS mRNA表达,缺血再灌注组、臭氧氧化预处理组和氧气预处理组eNOS mRNA表达增强,均高于假手术组（均P〈0.05）,臭氧氧化预处理组eNOS mRNA表达高于缺血再灌注组和氧气预处理组（均P〈0.05）.假手术组无明显eNOS蛋白表达,缺血再灌注组、臭氧氧化预处理组和氧气预处理组eNOS蛋白表达增强,均高于假手术组（均P〈0.05）,臭氧氧化预处理组eNOS蛋白表达高于缺血再灌注组和氧气预处理组（均P〈0.05）.结论 臭氧氧化预处理对大鼠肾缺血再灌注损伤有保护作用,作用机制可能与其诱导eNOS合成增多、一氧化氮产生增多有关.     

缺血后处理对大鼠肝缺血再灌注损伤早期的保护作用

目的 探讨缺血后处理（IPC）对大鼠肝脏缺血再灌注损伤早期的保护作用机理。方法 建立大鼠肝脏缺血再灌注模型，54只健康雄性SD大鼠随机分为假手术组（SO组）、对照组（IR组）和缺血后处理组（IPC组）。后处理组于完全再灌注前，给予多次短暂复灌复停作为缺血后处理。分别于再灌注后1h、3h及6h抽血进行血清ALT、AST活性及TNF-α表达测定，免疫组化测定肝脏NF-kB活性及ICAM-1的表达。结果 与SO组比较，IR组及IPC组再灌注后大鼠血清ALT、AST活性明显增高，肝脏NF-kB活性明显增强，TNF-α和ICAM-1表达也随之增加；同IR组相比，IPC组的血清ALT、AST活性明显降低，NF-kB活性及TNF-α和ICAM-1表达亦明显降低，差异均具有统计学意义（P〈0．01）。结论 缺血后处理能够减轻肝脏缺血再灌注损伤。其保护作用可能与通过抑制再灌注早期NF-kB的活性，降低了TNF-α和ICAM-1等炎性细胞因子水平有关。     

阿霉素诱导热休克蛋白72对大鼠肝脏冷缺血-再灌注损伤的保护作用

目的观察阿霉素（DXR）预处理诱导大鼠肝脏热休克反应在肝脏长时间冷缺血一再灌注损伤中对肝细胞的保护作用。方法供体大鼠术前按1mg／kg由外周静脉注射DXR（DXR组）,对照组注射生理盐水。48h后行肝脏原位冷灌注,获取肝脏后将其在4℃UW液中保存48h,然后行原位肝移植,再灌注1、3h。逆转录-聚合酶链反应法测定肝组织肿瘤坏死因子-α（TNF-α）mRNA、中性粒细胞化学趋化性细胞因子（CINC）mRNA、巨噬细胞炎症蛋白-2（MIP-2）mRNA的表达,蛋白质印迹法测定肝组织热休克蛋白72（HSP72）、核转录因子-κB（NF-κB）的表达,测定血清谷丙转氨酶、TNF-α、CINC、MIP-2水平。同时观察7d生存率。结果DXR组TNF-α mRNA、CINCmRNA、MIP-2mRNA的表达均低于对照组。DXR组HSP72表达显著,对照组基本无表达;DXR组NF-κB无表达,对照组显著表达。DXR组血清TNF-α、CINC、MIP-2显著低于对照组（P〈0．05）。DXR组7d生存率为50％,对照组为0（P〈0．05）。结论DXR预处理大鼠供肝可使肝脏长时间冷缺血-再灌注损伤显著减轻;HSP72的诱导可抑制NF-κB激活导致的炎症反应,对肝实质细胞提供保护作用。     

缺血预处理对大鼠皮瓣缺血再灌注后Bcl-2和Bax基因表达的影响

目的探讨缺血预处理（IPC）对大鼠皮瓣缺血再灌注（I／R）后凋亡相关蛋白表达的影响及其对皮瓣缺血再灌注损伤保护作用机制。方法采用Wistar大鼠为实验动物，制备右下腹岛状皮瓣I／R模型。90只大鼠随机分为对照组、I／R组和IPC组。采用SABC法观察IPC对大鼠皮瓣缺血再灌注后Bcl-2、Bax蛋白表达规律。结果SABC法观察显示Bcl-2在缺血再灌注后4h有少量表达，24h达峰值，7d时明显减少。IPC组再灌注后4h表达较弱，3d达峰值，7d时明显减弱。IPC组与I／R组比较，Bcl-2在I／R后3d差异有统计学意义（P〈0．01）。Bax基因在I／R后4h表达，3d时达峰值，7d时仍有较高水平表达；IPC组各时间点Bax基因呈低表达，与I／R组比较，3d和7d时差异最显著（P〈0．01）。结论IPC诱导Bcl-2基因表达增加和抑制Bax基因表达可能是IPC诱导抗凋亡、产生皮瓣保护机制的原因之一。     

大鼠肝缺血再灌注损伤NF-kB与ICAM-1在脑组织的表达及意义

目的：观察大鼠在肝脏缺血再灌注（IR）过程中肝脏炎性细胞因子TNF-α、IL-1βmRNA表达与脑组织NF-kB、ICAM-1表达之间的关系，探讨肝脏IR是否可导致脑组织损伤及其可能的机制。方法：选健康雄性Wister大鼠48只，随机分为对照组、缺血30min组（I组）、缺血30min再灌注组（IR组）、缺血30min再灌注后1h组（IR1h组）、缺血30min再灌注后2h组（IR2h组）、缺血30min再灌注后4h组（IR4h组），每组8只。应用免疫组化法分别检测各组大鼠肝脏TNF-α及脑皮质、海马和下丘脑区NF-kB、ICAM-1的表达情况，应用原位杂交的方法检测肝脏IL-1βmRNA表达情况。结果：肝脏IR导致肝脏明显的损伤，表现为血清GPT、AKP、γ-GT升高（P〈0．01），肝组织中TNF-α、IL-1βmRNA表达显著增N（P〈0．01），肝细胞水肿，炎性细胞浸润，甚至细胞坏死。随着再灌注时间的延长，脑组织HE染色可见脑细胞水肿，甚至个别脑细胞坏死。与对照组比较，I组和IR组大鼠脑皮质、海马和下丘脑中NF-kB、ICAM-1表达的差异无统计学意义（P〉0．05），IR1h组、IR2h组和IR4h组的差异有统计学意义（P〈0．05，P〈0．01）。IR1h、IR2h、IR4h组与对照组、I组、IR组比较，各部位脑组织NF-kB、ICAM-1的表达显著增N（P〈0．05或P〈0．01）。各组大鼠不同部位脑组织间NF-kB、ICAM-1表达无统计学意义（P〉0．05）。结论：肝脏IR对脑组织可产生损伤性影响，NF-kB、ICAM-1介导的炎性细胞反应，参与了脑组织损伤的发生机制。     

缺血后处理对缺血再灌注大鼠肝细胞即刻早期基因c-fos和c-jun表达的影响

目的 观察缺血后处理对大鼠肝脏缺血再灌注损伤的影响。方法 120只Wistar大鼠随机分为缺血再灌注组（IRI），缺血后处理组（IPO）和假手术组（S），于复灌后0，0．5，1，2，4，8，12，24h取材，应用RT-PCR法检测各组c-fos，c-jun mRNA的表达。结果 （1）在IRI组再灌注后0．5～2h，c-fos和c—jun的表达均增高，1h达高峰；4h后仅c-jun有持续较高的表达，c—fos的表达开始下降；（2）IPO组各时点c-fos mRNA的表达均较IRI组低，但无统计学差异（P〉0．05）；（3）与IRI组相比，IPO组c-jun mRNA在0．5，1h和2h组明显降低（P〈0．05）。结论 缺血后处理能有效地保护肝脏免受缺血再灌注造成的损伤，这种保护效应的机制可能与影响即早基因的转录有关。     

缺血预处理对肾脏的保护作用及其机制的实验研究

目的：在肾脏缺血预处理的动物实验模型中，探讨缺血预处理对肾脏的保护作用及其机制。方法：将36只小白兔随机分为4组，即对照组，缺血预处理组（IP），缺血再灌注组（I／R）和缺血预处理后再灌注组（IP＋I／R），分别检测各组动物血液中肌酐（Cr)和一氧化氮（NO）浓度，肾组织中一氧化氮合酶（NOS,eNOS，iNOS,nNOS)在肾组织中的表达及组织学变化。结果：急性肾缺血60min再灌注60min时，发现IP组及IP＋I／R组血液中Cr浓度变化与对照组之间差异无显著性意义（P＞0．05），但明显低于I／R组（P＜0．05），在IP组和IP＋I／R组血液中，NO浓度明显高于对照组和I／R组，eNOS阳性表达在IP组和IP＋I／R组明显高于I／R组和对照组（P＜0．01），iNOS和nNOS在肾组织中未见明显表达，组织学变化发现I／R组肾细胞发生明显变性坏死，而IP组和对照组未见明显改变，结论：缺血预处理在肾脏缺血再灌注中具有保护作用。而NOS可能参与了该作用机制。     

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.     

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.     

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.