不同器官保存液对大鼠肝脏缺血再灌注损伤时嘌呤核苷磷酸酶活性和透明质酸吸收率的影响

目的 探讨大鼠肝脏低温保存及常温缺血再灌注过程中在不同的保存液中嘌呤核苷磷酸酶(PNP)活性和透明质酸(HA)吸收率的变化.方法 将大鼠肝脏在三种不同保存液中低温保存16 h和24 h后,用37℃Krebs-Henseleit液连续循环灌注90 min,分别于不同灌注时间检测灌洗液中PNP活性和外源性透明质酸的吸收率的变化.结果 经过16 h的低温保存后,再灌注60 min前,HTK保存的肝脏中PNP明显高于uw和Celsior;60 min后HTK和Celsior保存的肝脏中PNP明显高于UW;经过24 h的低温保存后,再灌注15 min后,HTK保存的肝脏中PNP明显高于Celsior,而Celsior又明显高于UW.低温保存16 h后,再灌注时,3种保存液保存的肝脏对外源性透明质酸的吸收率均为负值,表明肝窦内皮细胞受到一定程度的损伤;保存24 h者,UW液保存肝脏外源性透明质酸的吸收率明显高于Celsior液和HTK液.结论 随着低温保存和再灌注时间的延长,大鼠肝脏中PNP活性逐渐增高,而外源性透明质酸的吸收率下降;二者可作为评价肝脏缺血再灌注损伤的指标.     

冷冻保存大鼠肝脏离体再灌注时嘌呤核苷磷酸酶活性和透明质酸吸收率的变化

目的探讨不同保存液保存大鼠肝脏后离体再灌注时嘌呤核苷磷酸酶(PNP)活性和透明质酸吸收率的变化及意义。方法分别采用UW液、HTK液和Celsior液灌洗、冷保存Wistar大鼠肝脏16及24 h,然后用37℃的Kreb-Henseleit液在常温下连续灌注90 min,分别于灌注0、15、30、60和90 min时,从灌注液中取样,测定嘌呤核苷磷酸酶活性和外源性透明质酸吸收率的变化,据此评价肝窦内皮细胞的状况。结果经过16 h的低温保存,在再灌注60 min以前,HTK液组灌注液中PNP的含量明显高于UW液组和Celsior液组(P<0.01);再灌注60 min后,HTK液组和Celsior液组灌注液中PNP的含量明显高于UW液组(P<0.01)。经过24 h的低温保存,在再灌注15 min后,HTK液组灌注液中PNP含量明显高于Celsior液组(P<0.01),而Celsior液组又明显高于UW液组(P<0.01)。透明质酸的吸收率均为负值,说明内源性透明质酸的释放大于外源性透明质酸的吸收,且随着保存时间和再灌注时间的延长,这一趋势更加明显,其中HTK液组最明显,Celsior液组次之。结论随着低温保存和再灌注时间的延长,肝脏中PNP活性逐渐升高,外源性透明质酸的吸收率下降,二者可作为评价肝脏缺血-再灌注损伤的指标。     

大鼠肝脏缺血再灌注损伤后5′核苷酸酶和乳酸脱氢酶活性变化的研究

目的探讨大鼠肝脏经过UW、Celsior和HTK三种不同类型保存液低温保存和常温再灌注后5′核苷酸酶和乳酸脱氢酶活性的变化.方法将大鼠肝脏在UW、Celsior和HTK液中低温4℃保存0、8、16和24 h后,采用离体连续灌注模型,用Krebs-Henseleit液37℃连续循环灌注90 min,灌注结束后取肝脏组织标本测定5′核苷酸酶和乳酸脱氢酶活性,并测定胆汁分泌量的变化.结果经过16和24 h的UW和Celsior低温保存后的肝组织5′核苷酸酶和乳酸脱氢酶的活性出现降低;HTK组8 h就出现降低.UW和Celsior组经过24 h的低温保存后,胆汁分泌量开始明显降低;在HTK组16 h后,胆汁分泌量就显著降低.结论 5′核苷酸酶和乳酸脱氢酶的活性随着低温缺血时间的延长逐渐降低;UW和Celsior液对肝窦内皮细胞和肝实质细胞的保护作用均强于HTK.     

大鼠肝脏缺血再灌注损伤后5′核苷酸酶和乳酸脱氢酶活化变化的研究

目的 探讨大鼠肝脏经过UW、Celsior和HTK三种不同类型保存液低浊保存和常温再灌注后5′核苷酸酶和乳酸脱氢酶活性的变化。方法 将大鼠肝脏在UW、Celsior和HTK液中低温4℃保存0、8、16、和24h后,采用离体连续灌注模型,用Krebs-Henseleit液37℃连续循环灌注90min,灌注结束后取肝脏组织标本测定5′核苷酸酶和乳酸脱氢酶活性,并测定胆汁分泌量的变化。结果 经过16和24h的UW和Celsior低温保存后的肝组织5′核式酸酶和乳酸脱氢酶的活性出现降低;HTK组8h就出现降低,UW和Celsior组经过24h的低温保存后,胆汁分泌量开始明显;在HTK组16h后,胆汁分泌量就显著降低。结论 5′核苷酸酶和乳酸脱氢酶的活性随着低温缺血时间的延长逐渐降低;UW和Celsior液以肝窦内皮细胞和肝实质细胞的保护作用均强于HTK。     

FK506对肝脏保存再灌注中肝窦内皮细胞损伤的保护作用

目的 探讨他克莫司（FK506）对肝脏低温保存再灌注中肝窦内皮细胞损伤的保护作用。方法 应用离体鼠肝脏保存再灌注模型,测定保存不同的时间后肝脏灌注流出液中内皮素（ET）及丙氨酸转氨酶（ALT）的含量以及透明质酸（HA）的摄取量,光镜及电镜下观察肝窦内皮细胞的形态学改变,比较分析FK506对上述指标的影响。结果 对照组随肝脏保存再灌注时间延长,灌注流出液中ET含量明显升高（P＜0．05）,HA摄取明显降低（P＜0．05）,并伴随ALT活性显著增高（P＜0．05）和肝窦内皮细胞形态学的异常改变;保存液和灌注液中均加入FK506后,上述指标异常变化均明显减轻,其差异有显著性（P＜0．05）。结论 FK506对离体大鼠肝脏肝窦内皮细胞的再灌注损伤有保护作用。     

尿胰蛋白酶抑制剂对肝脏保存再灌注中肝窦内皮细胞损伤的保护作用

目的　探讨尿胰蛋白酶抑制剂 (UTI)对肝脏低温保存再灌注中窦内皮细胞损伤的保护作用。方法　应用离体大鼠肝脏保存再灌注模型 ,测定保存 12 h、2 4 h,再灌注 30 min流出液中内皮素 (ET)、丙氨酸转氨酶 (AL T)、天冬氨酸转氨酶(AST)、乳酸脱氢酶 (L DH)的活性、透明脂酸 (HA)的摄取量以及肝组织中髓过氧化物酶 (MPO)水平 ,光镜下观察肝窦内皮细胞的形态学改变 ,比较分析 U TI(10 0 U/ m l)对上述指标的影响。结果　对照组肝脏保存再灌注流出液中 ET含量明显升高 (P<0 .0 5 ) ,HA摄取明显降低 (P<0 .0 5 ) ,并伴随 AL T、AST、L DH、MPO水平显著增高和肝窦内皮细胞形态学的异常改变 ;保存液中加入 UTI后 ,上述指标异常变化均明显减轻 ,其差异具有显著性 (P<0 .0 5 )。结论　 UTI对离体大鼠肝脏窦内皮细胞的保存再灌注损伤有保护作用     

三甲氧苄嗪对大鼠心脏保存作用的实验研究

目的 探讨UW、HTK器官保存液以及加入三甲氧苄嗪（TMZ）对大鼠心脏离体低温保存的保护效果。方法 以离体灌注鼠心为研究对象，观察鼠心在UW、HTK保存液中4℃保存8h后，以及在UW液、HTK液中加入10^-6mol/L TMZ后的心功能、心肌ATP及乳酸盐的变化。结果 HTK液保存的心脏，心功能恢复明显优于UW液（P＜0．05），心肌ATP储存量多于UW液（P＜0．05），心肌乳酸盐含量少于UW液（P＜0．05）；在UW液、HTK液中加入10^-6mol/L TMZ后，可显著提高UW、HTK液的心肌保护效果（P＜0．05）。结论 HTK液对离体低温保存鼠心的心肌保护效果优于UW液；TMZ能显著提高UW、HTK保存液的心肌保护效果。     

HTK液和Celsior液在肝移植中的应用研究

目前 ,UW液是器官移植中常用的多器官保存液 ,同时临床应用经验和前瞻性研究表明 ,HTK液和Celsior液在肝脏移植中的应用安全有效 ,是UW液可靠的替代选择。实验研究发现 ,上述两种保存液可以减轻低温缺血和再灌注损伤 ,改善器官保存效果。本文对近期HTK和Celsior保存液临床应用及实验研究进展作一综述     

不同胆道灌洗方法对大鼠肝内胆管冷保存再灌注损伤的影响

目的观察不同胆道灌洗方法对大鼠移植肝肝内胆管冷保存再灌注损伤的影响。方法应用大鼠原位肝移植模型，将88只SD大鼠随机分为假手术组、胆道非灌洗组、UW液胆道灌洗组、生理盐水（NS）胆道灌洗＋UW液肝内胆道灌注保存组、HTK液胆道灌洗＋UW液肝内胆道灌注保存组、HTK液胆道灌洗＋HTK液肝内胆道灌注保存组。移植肝置于4℃林格液中保存2h后行原位肝移植。移植肝再灌注后24h，检测血清总胆红素（TB）、直接胆红素（DB）、碱性磷酸酶（AKP）、γ-谷酰转肽酶（GGT）及胆汁中GGT、葡萄糖（Glu）含量。在光镜及电镜下观察肝内胆管上皮细胞的形态学变化。结果与非灌洗组比较，胆道灌洗组术后各项指标明显改善（P〈0．01）；HTK液及NS灌洗组较UW液灌洗组术后指标改善明显（P〈0．05）。病理检测发现非灌洗组胆道损伤明显，各灌洗组胆道损伤程度明显改善，HTK液灌洗＋UW或HTK液灌注组对胆管上皮细胞的损伤较轻。结论移植肝冷保存前进行胆道灌洗可以明显减轻胆管上皮细胞的损伤，4℃HTK液灌洗＋4℃UW或HTK液灌注保存效果比较理想。     

HTK液和Celsior液在肝移植中的应用研究

目前，UW液是器官移植中常用的多器官保存液，同时临床应用经验和前瞻性研究表明，HTK液和Celsior液在肝脏移植中的应用安全有效，是UW液可靠的替代选择。实验研究发现，上述两种保存液可以减轻低温缺血和再灌注损伤，改善器官保存效果。本文对近期HTK和Celsior保存液临床应用及实验研究进展作一综述。     

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.     

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.