NO代谢途径干预对肥胖大鼠术后胰岛素敏感性的影响

目的 探讨一氧化氮（NO）代谢途径干预对肥胖大鼠术后胰岛素敏感性的影响。方法 对2005年5月时2006年1月建立的肥胖大鼠小肠切除模型资料进行分析，随机分为正常对照组、L-硝基-精氨酸甲酯（L-NAME）处理组、L-精氨酸（L-Arg）处理组、L-Arg＋L-NAME处理组，术后给予NO代谢途径干预，通过血清NO质量浓度和血糖检测以及胰岛素敏感性实验，对肥胖大鼠术后NO代谢途径与胰岛素敏感性的相关性进行分析。结果 L-硝基-精氨酸甲酯处理组与对照组相比血糖较高，血清NO质量浓度及胰岛素敏感性降低（P〈0.05），L-精氨酸处理组则相反，L-Arg＋L-NAME处理组和正常对照组相比各项指标差异无显著性。结论 NO代谢途径与肥胖大鼠术后胰岛素敏感性有着显著的相关性，NO代谢途径干预改变了肥胖大鼠术后的胰岛素敏感性。     

大鼠肝缺血／再灌注后肝组织一氧化氮和不同亚型一氧化氮合酶的变化

目的探讨一氧化氮（NO）和一氧化氮合成酶（NOS）在肝缺血／再灌注（I／R）过程中的变化和作用。方法健康雄性SD大鼠24只，随机分为3组（每组8只）：①正常对照组，术中只分离肝周围韧带，不做肝门阻断及再灌注。②I/R组，进行45min的部分肝门阻断及60min的再灌注。③L-精氨酸（L—Arg）组，缺血前20min经阴茎背静脉注射L—Arg（300mg／kg），余同②组。实验结束后，取下腔静脉血2ml，并迅速切取缺血肝组织。检测血清丙氨酸转氨酶（ALT）、门冬氨酸转氨酶（AST）、乳酸脱氢酶（LDH）；测定肝组织中超氧化物歧化酶（SOD）、丙二醛（MDA）、黄嘌呤氧化酶（XOD）、一氧化氮（NO）和一氧化氯合成酶（NOS）等指标；观察光镜和电镜下肝组织学变化。结果与正常对照组相比，I／R组iNOS升高，NO降低；L-Arg组NO、eNOS均高于I／R组。2、3组比1组大鼠的肝组织病理损害重、肝功能差，L—Arg组病理损害较I／R组明显减轻、肝功能改善。结论NO对大鼠肝I／R损伤具有保护作用．不同亚型NOS的变化参与其中。     

供肝缺血预处理对大鼠肝移植缺血再灌注损伤的保护性作用

目的：探讨供肝热缺血预处理对大鼠供肝冷缺血再灌注（I/R）损伤中的保护作用及其机制。方法：采用SD大鼠建立原位肝移植动物模型，供肝冷缺血期为120 min，受体无肝期16～20min。随机分为3组：假手术组，获取供肝前仅作肝脏周围韧带的解剖;肝移植组，获取供肝前不作肝门阻断;缺血预处理（IPC）组，获取供肝前阻断肝门5min，再灌注5min。术后2，4，24，72h检测血清ALT、抗氧化酶活力、血清NO水平及细胞因子TNF-α。结果：肝移植组及IPC组术后ALT及过氧化物含量均明显高于假手术组，而IPC组低于肝移植组(P﹤0.05)，其抗氧化酶活力较移植组明显升高（P﹤0.05）; NO水平在IPC术后2，4，24，72h均显著高于假手术组，72h时肝移植组明显高于IPC组及假手术组(P﹤0.05)，而IPC组高于假手术组;肝移植组血清中TNF-α释放明显高于假手术组(P﹤0.05);IPC组TNF-α的释放显著低于肝移植组(P﹤0.05)。结论：供肝热缺血预处理对大鼠供肝冷缺血I/R损伤具有明显保护作用;其机制可能是IPC快速提高并稳定了血清中NO水平，降低了炎性细胞因子TNF-a的产生，从而减少移植肝细胞的损害。     

一氧化氮与大鼠胰十二指肠移植中的急性肺损伤

器官移植研究中发现,移植物的缺血再灌注可造成远位多脏器的损害[1-3].胰腺移植中胰腺的缺血再灌注是否会造成急性肺损伤(ALI),尚未引起足够重视.我们在大鼠胰十二指肠移植模型中探讨是否发生ALI,并以L-精氨酸( L-Arg)和L-硝基精氨酸甲酯(L-NAME)作为实验干预,探讨一氧化氮(N0)在ALI中的作用及机制.     

福尔马林致痛对大鼠行为学及脊髓NO的影响

目的：探讨大鼠福尔马林致痛模型脊髓背角一氧化氮合酶(NOS)的变化。方法：雄性SD大鼠64只，随机分为四组：生理盐水对照组(NS组)、福尔马林对照组(F组)、L-精氨酸组(LaF组)和L-NG-硝基精氨酸甲酯(LnF组)组。F组给予5％福尔马林100μl足底注射；LaF和LnF组在同F组处理前分别给予L-精氨酸(L-Arg)和L-NG-硝基精氨酸甲酯(L-NAME)。在福尔马林处理后30min、O～1h分别检测大鼠脊髓NOS的表达及观察大鼠的行为学表现。结果：F组的缩腿舔爪时间和脊髓的NOS表达显著长于、强于NS组；预先给予L-Arg或L-NAME分别能加强或抑制以上作用。结论：福尔马林致痛能引起大鼠脊髓背角一氧化氮(NO)的释放，可能是其产生伤害作用的机制之一。     

L-精氨酸预处理对大鼠小肠移植缺血再灌注损伤的影响

我们应用大鼠小肠移植模型，在供肠获取前不同时间点给予供体L-精氨酸（L-Arg），观察其对缺血．再灌注损伤（IRI）小肠细胞凋亡的影响，现将结果报道如下。     

血浆一氧化氮对大鼠肝缺血预处理的影响

目的：探讨促进或抑制一氧化氮（NO）的合成对大鼠肝脏缺血预处理（IPC）保护作用的影响。方法：大鼠肝脏经缺血再灌注（I／R，R组）、IPC（P组）、左旋精氨酸（L－Arg，A组）促进或左旋单甲基精氨酸（L－NMMA，N组）抑制NO合成及假手术（C组）后，观察2、24h及1周后血浆NO、天冬氨酸氨基转移酶（AST）及丙氨酸氨基转移酶（ALT）以及大鼠死亡率及肝脏组织病理改变。结果：A组累计死亡率低于R组及N组（P＜0．05）。A组NO水平在2h后明显高于P组（P＜0．01）；N组在2h及24h后均低于P组（P＜0．05）及A组（P＜0．01），1周后与P组、A组及R组差异无显著性（P＞0．01），但明显高于C组。A组及P组的血浆ALT在2h及24h后均显著低于N组（P＜0．05），而N组与R组差异无显著性（P＞0．05），1周后，A组、P组及N组间差异无显著性，均低于R组（P＜0．05）。结论：增加NO的产生，可以明显增强IPC对肝脏的保护作用，抑制NO合成并不能完全阻断这种保护作用，提示NO是IPC保护机制中的一个重要但非唯一的因素。     

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。     

不同方案缺血预处理对大鼠横形腹直肌肌皮瓣再灌注损伤的影响

目的 探讨不同方案缺血预处理（ischemic preconditioning，IPC）对大鼠横形腹直肌肌皮瓣（transverse rectus abdominis musculocutaneous flap，TRAM）移植后再灌注损伤的影响。方法选取雄性Wistar大鼠90只，建立TRAM模型，随机分为对照组和实验组，对照组10只，无需预处理过程，持续缺血4h后，恢复肌皮瓣血供；实验组分为8个亚组，每组10只，以微血管夹阻断腹壁下血管5min，再恢复血流5min，处理1次为sIPC5／5组，处理2次为bIPC5／5组，依次为sIPC5／10组（缺血5min／再灌注10min1次）、bIPC5／10组（缺血5min／再灌注10min2次）、sIPC10／5组（缺血10min／再灌注5min 1次）、bIPC 10／5组（缺血10min／再灌注5min2次）、sIPC10／10组（缺血10min／再灌注10min1次）、bIPC10／10组（缺血10min／再灌注10min2次），其余实验步骤与对照组相同；每组肌皮瓣恢复血供4h后，取3只处死取材，测定肌组织含水量及HE染色镜检观察骨骼肌组织结构，其余动物于术后第7天判断皮瓣成活情况，计算成活面积百分比。结果恢复血供12h后，各实验组肌皮瓣两侧边缘部分肿胀，色泽黯淡，较对照组肿胀范围小，程度轻；光镜下见各实验组肌纤维轻度肿胀，染色均一，肌纤维结构尚完整，胞核呈梭形，无明显肿胀。对照组肿胀明显，部分肌纤维断裂。各实验组与对照组相比肌组织水含量明显减少（P〈0．001），皮瓣成活面积提高了2～3倍（P〈0.001）。两次预处理对肌皮瓣成活面积的影响与相应的单次预处理比较，差异有统计学意义（P〈0．05）。结论IPC可明显减轻大鼠TRAM再灌注损伤程度，其保护效应受缺血／再灌注时间、处理次数等因素的影响。     

一氧化氮对大鼠肝脏缺血再灌注后白细胞-内皮细胞粘附的影响

本文复制大鼠肝脏原位隔离冷灌注模型，利用一氧化氮合酶(NOS)的增强剂L-精氨酸(L-arg)和抑制剂N-硝基-L-精氨酸甲酯(L-NAME)，探讨了大鼠肝脏缺血再灌注后NO的作用机制。     

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.