控制性再灌注防止肺再灌注损伤的研究

目的　探讨控制性再灌注在预防肺缺血再灌注 (I/R)损伤中的作用及其机制。方法将猪分为 2组 ,10只猪切取左肺作供体 ,4℃改良的E C液灌洗和保存 ,4h后进行左肺移植。对照组常规操作 ,实验组采用控制性再灌注 :灌注液 (去白细胞血 :改良Buckberg液 =4∶1) ;灌注压 2 0mmHg ;灌注时间 10min。 0 .5、1和 2h后测血氧分压、肺血管阻力、肺顺应性、一氧化氮 (NO)含量、丙二醛 (MDA)含量、肺干 /湿重比。结果　实验组的左肺氧合功能 ,肺顺应性明显好于对照组 ,肺循环阻力、MDA值及肺含水量均低于对照组 (P <0 .0 1) ;实验组肺中NO含量较对照组明显升高 (P <0 .0 1)。结论　控制性再灌注能明显降低肺I/R损伤 ,起到了较好的移植肺保护效果。     

L－精氨酸在离体肺保存中的作用

目的：研究一氧化氮前体L－精氨酸（L-Arg)在离体兔肺保存中的保护作用。方法：将14只新西兰兔随机分为2组,对照组以改良的Euro-Collins(ECS)液灌注及保存供肺,实验组以L－精氨酸（3mmol/L)加入改良的ECS液中灌注及保存供肺。冷保存6h。以自体血再灌注1h后,做肺静脉血气分析（PvO2),并测定血及肺组织中一氧化 氮（NO）,超氧化物歧化酶（SOD）,脂质过氧化物（LPO）含量及肺组织的超微结构以评价肺保护的效果。结果：再灌注后,实验组比对照组血氧分压显著提高（P＜0．05）。实验组血及肺组织中NO及SOD含量较对照组高（P＜0．05）,LPO含量较对照组低（P＜0．05）,透射电镜检查实验组损伤轻于对照组,结论：肺保存不超过6h时,在改良的ECS液中加入L-Arg用于离体肺的灌注和保存,能减轻肺损伤。     

二种不同成份灌洗液保存效果的对比

目的 比较２种不同成份肺灌液的肺保存效果。方法 将犬分成２组,一组供肺采用改良的Ｅｕｒｏ－Ｃｏｌｌｉｎｓ液灌洗,另一组用低钾葡萄糖液（ＬＰＧ液,钾浓度４ｍｍｏｌ／Ｌ灌洗）,４℃保存６小时后行异体左肺移植,保留受体的右肺。术后１０分钟－７２小时定时阻断右肺动血液,采股动脉血作血液气体分析。并作病理检查。结果 改良的Ｅｕｒｏ－Ｃｏｌｌｉｎｓ液和ＬＰＧ液灌洗的肺移植后即刻受体动脉血氧分压（ＰａＯ２）分别     

二肽酰肽酶Ⅳ抑制剂灌洗、保存供肺对大鼠移植肺功能的影响

目的 探讨二肽酰肽酶Ⅳ(DPPⅣ酶)抑制剂灌洗、保存供肺对大鼠移植肺功能的影响.方法 将纯系SD大鼠随机分为6组,供、受者均为SD大鼠.对照组1和对照组2的供肺用低钾右旋糖苷液(LPD液)灌洗,并保存18 h,然后行左肺移植,于移植后1 d测定对照组1受者的气道峰压(PIP)、静脉血氧分压(POe)、移植肺湿干重比(W/D)、髓过氧化物酶(MPO)活性和丙二醛(MDA)含量,对照组2用于观察术后7 d存活率;共设4个实验组(实验组1～实验组4),供肺用含特异性不可逆DPPⅣ酶抑制剂的LPD液灌洗,并保存18 h,然后行左肺移植,分别于移植后1(实验组1)、3(实验组2)、5(实验组3)和7 d(实验组4)测定受者的各项肺功能指标.结果 对照组2大鼠至术后第7天全部死亡,实验组4的大鼠均存活至术后第7天.与对照组1比较,各实验组的PIP值降低(P<0.05),PO2值升高(P<0.05),W/D值降低(P<0.05),MPO活性及MDA含量降低(P<0.05),差异有统计学意义,并且随着时间的推移,实验组的上述指标不断改善,至术后第7天,各项检测值接近正常.结论 以特异性不可逆DPPⅣ酶活性抑制剂灌洗、保存供肺能显著减轻移植肺的缺血再灌注损伤,有利于移植肺功能的恢复.     

长征-1号多器官保存液低温保存大鼠肺脏并移植的实验研究

目的 通过大鼠原位肺移模型,研究长征－１号多器官保存液保存肺的效果。方法 将大鼠随机分为３组;对组照;以平衡液灌洗供肺,并立即移植;ＣＺ－１液组;以ＣＺ－１液灌洗供肺,保存８小时后移植;Ｅｕｒｏ－Ｃｏｌｌｉｎｓ液组,以Ｅｕｒｏ－Ｃｏｌｌｉｎｓ液灌洗供肺,保存８小时后移植。     

缓激肽β2受体拮抗剂在大鼠肺移植缺血再灌注损伤中的保护作用

目的 探讨缓激肽β2受体拮抗剂（HOE-140）对大鼠移植肺功能的影响以及作用.方法 将纯系SD大鼠随机分为3组,即实验组1、实验组2、对照组.对照组的供肺用低钾右旋糖苷液（LPD液）灌洗,并保存18h,然后行左肺移植,于移植后1d测定对照组的气道峰压（PAP）、静脉血氧分压（PO2）、移植肺湿干重比（W/D）、髓过氧化物酶（MPO）活性.实验组1以及实验组2（加HOE-140干预）的供肺用含特异性不可逆DPPⅣ酶抑制剂（AB192）的LPD液灌洗,并保存18h,然后行左肺移植,分别于移植后1d测定受者的各项肺功能指标,并取相同受体肺部组织做病理学检查. 结果 与对照组比较,各实验组的PAP值降低（P＜0.05）,PO2值升高（P＜0.05）,W/D值降低（P＜0.05）,MPO活性降低（P＜0.05）,差异有统计学意义,病理学结果显示实验组2（HOE-140组）均优于对照组及实验组1.结论 缓激肽β2 受体拮抗剂HOE-140能有效降低肺移植肺缺血再灌注损伤,从而改善移植肺功能.     

硝酸甘油对移植犬肺的保护作用

目的评价硝酸甘油对犬肺的保护作用。方法将24只犬随机分为实验组和对照组两组,每组供、受体各6只。实验组用含硝酸甘油的低钾右旋糖酐(low potassium dextran,LPD)灌注液灌注供肺,对照组仅用LPD灌注液灌注供肺,留取供犬右肺继续于灌注液中保存至4h,修剪左肺作移植肺,两组受体犬均行左肺移植术。比较两组供体肺组织不同时间的髓过氧化酶(myeloperoxi-dase,MPO)活性、丙二醛(malondialdehyde,MDA)含量和湿/干重量比(W/D),比较两组受体犬移植前后不同时间肺血流动力学参数以及血气分析指标,并比较病理结果。结果与对照组相比,实验组肺组织灌注后各时间段的MPO活性、丙二醛含量均较低(均为P(0.05),两组W/D差异无统计学意义。实验组受体犬移植后的平均肺动脉压(mean pulmonary arterial pressure,MPAP)低于对照组而动脉血氧分压(PaO2)高于对照组(均为P(0.05)。移植后供肺肺组织的病理学结果显示,实验组肺组织水肿、炎性细胞浸润、损伤等病理变化较对照组减轻。结论在本实验条件下,在灌注液中加入硝酸甘油可以在犬肺移植过程中起到保护肺组织的作用。     

前列腺素E1及硝酸甘油在离体脑保护中应用的实验研究

应用兔离体肺再灌注模型研究前列腺素Ｅ１（ＰＧＥ１）及硝酸甘油ＮＴＧ）在离体肺保护中的作用。１８只随机平均分为两组，对照组以ＬＰＤ液进行肺灌洗及保存，用药组以ＰＧＥ１１００μｇ．Ｌ＾－１及ＮＴＧ１０ｍｇ．Ｌ＾－１加入ＬＰＤ液中进行肺灌洗及保存。每组再分为三小组分别保存２、４、８小时后进行再灌注，测定再灌注后肺血管阻力（ＰＶＲ）、肺通所阻力ＬＲ，肺含水量及动脉发压以了解肺保护效果。结果示；用药组再灌注     

内源性一氧化氮在非创伤性缺血预处理中对兔肺的保护作用

目的探讨内源性一氧化氮（NO）在非创伤性缺血预处理（N—WIP）中对兔肺缺血／再灌注（I／R）损伤的保护作用及可能机制。方法采用N-WIP及经典缺血预处理（C-IP）的动物模型，比较两种缺血预处理方法中内源性NO对兔肺在缺血／再灌注损伤中的保护效应。将40只大白兔随机平均分为4组：对照组、I／R组、C—IP组和NWIP组。对比观察各组血清及肺组织中NO2^-／NO3^-、丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性以及肺湿／干重比。结果N—WIP组和C-IP组的兔肺再灌注后NO2^-／NO3^-含量均高于I／R组（P〈0．01），甚至高于对照组（P〈0．05）。两种缺血预处理组SOD活性均高于I／R组（P〈0．01），肺湿／干重比和MDA含量均低于I／R组（P〈0．05，P〈0．01）。结论N-WIP与C-IP对移植肺在缺血／再灌注损伤中具有同等强度的保护作用。其机制可能是通过诱发内源性一氧化氮（NO）舒张血管，从而起到保护血管内皮的效应。     

硝普钠在预防肺缺血再灌注损伤中的作用及机制

目的探讨硝普钠在预防肺缺血再灌注损伤中的作用及其机制。方法将14头猪随机平均分为对照组和实验组。对照组:在去除肺动脉阻断,恢复自体血流前,给予控制性再灌注[用35℃-37℃再灌注液(去白细胞:改良Buckberg液=4:1),灌注压18 mm Hg,灌注时间10min]。实验组:在去除肺动脉阻断,恢复自体血流前,给予控制性再灌注;后经肺动脉注入硝普钠1.0μg·kg-1·min-1 ×10min。0.5、1和2 h后测两组的血氧分压、肺血管阻力、肺顺应性及肺氧合功能变化;实验结束后,取肺组织测一氧化氮(NO)含量、丙二醛(MDA)含量及肺含水量。结果实验组的左肺氧合功能和肺顺应性明显好于对照组(P<0.05)。肺循环阻力、MDA含量及肺含水量均低于对照组(P <0.01)。实验组和对照组肺组织中NO含量分别为:(114.41±6.77)μmol/L和(56.67±7.42) μmol/L,实验组较对照组明显升高(P<0.01)。结论硝普钠可使肺组织中NO含量显著升高,有效的预防了肺缺血再灌注损伤。     

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.     

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.     

Immunomodulation in Transplantation with Photopheresis

Abstract: Photopheresis is a technique in which peripheral blood mononuclear cells, in the presence of a photoacti-vatable compound, are exposed extracorporeally to ultraviolet A light and reinfused, inducing a host autoregula-tory immune response. Experimental work and ongoing clinical studies are helping to define the role of this novel, safe, and non-toxic immunomodulating technology in the field of transplantation.