磁性靶向材料介导骨髓间充质干细胞经静脉移植修复梗死心肌

目的探讨用磁性靶向材料介导骨髓间充质干细胞（MSCs）经静脉移植时到达心肌梗死部位的程度以及对心肌梗死修复的影响。方法取体外扩增的第4代MSCs，先测定MSCs的表面标记，用含10μmol的5-氮杂胞苷诱导后，将MSCs细胞核DAPI（4，6-联脒-2-苯基吲哚）染色后备用移植。将28只SD大鼠分为3组，A组：10只，磁性靶向材料和MSCs接触结合后经大鼠尾静脉移植，将磁石接触心肌梗死部位皮肤表面30min后继续饲养；B组：9只，未与磁性靶向材料结合的MSCs经大鼠尾静脉移植；C组：9只，将MScs直接移植心肌梗死部位。于移植2d后检查MSCs在梗死部位聚集的情况，30d后检查心肌梗死部位的功能及形态的改变。结果在透射电子显微镜下观察可见3～5个磁性靶向材料分子和MSCs的细胞膜结合。A组MSCs归巢率为38％，B组6％，C组53％，A组和C组聚集MSC数目明显多于B组（P〈0．01）。A组和C组移植后左心室射血分数（LVEF）、左心室短轴缩短率（LVFS）较移植前明显改善（LVEF46％±6％VS．38％±8％，51％±5％ vs．35％±4％；LVFS28％±6％vs．20％±7％，32％±4％vs．20％±5％，P〈0．05）；光学显微镜下观察梗死心肌内均可找到标记DAPI的移植细胞。B组移植后左心室收缩功能各项指标无明显改善，光学显微镜下在梗死心肌内未找到标记了DAPI的移植细胞（MSCs归巢率为38％）。C组与A组结果比较差异无统计学意义，但实验过程中死亡率较高。结论磁性靶向材料介导MSCs经静脉移植方法能聚集更多的MSCs于梗死心肌部位，减小梗死区面积，有效改善心肌梗死后的心功能。     

骨髓基质干细胞治疗兔缺血心肌的初步实验研究

目的通过建立兔自体骨髓移植模型,验证骨髓基质干细胞(MSCs)移植到缺血心肌后是否在心肌的微环境中可以向心肌细胞分化,探讨其对缺血心肌心功能的影响。方法将13只新西兰大白兔分为实验组(7只)和对照组(6只),实验组于心肌梗死前后缘上、中、下各3点分别注射被5溴-2脱氧尿苷(BrdU)标记的自体MSCs(3×106cells/30μl);对照组注射同等量的磷酸盐缓冲液(PBS)。移植4周后通过激光共聚焦显微镜验证移植后的MSCs是否向心肌细胞分化,并用心脏彩色超声心动图和多导生理记录仪测定缺血心肌的心功能。结果移植4周后,MSCs向心肌细胞分化,表达出α-肌小节肌动蛋白(-αsarcomeric actin)和存在于闰盘中的连接蛋白43(connexin 43),自体MSCs能够增加局部心肌组织中血管数量。实验组心肌左心室收缩功能明显比对照组增强[左心室射血分数(LVEF):0.51±0.07 vs.0.43±0.06,左心室侧壁运动幅度(LVLWMD):1.75±0.42mm vs.1.09±0.28mm,左心室收缩期室壁增厚率(LVΔT):0.19%±0.05%vs.0.11%±0.04%,左心室收缩压(LVSP):113.1±6.3 mmHg vs.99.5±5.1 mmHg,左心室舒张期末压(LVEDP):11.5±2.1 mmHg vs.14.3±3.1mmHg,左心室压力增高最大速率(+dp/dtmax):4 618.3±365.2mmHg/s vs.3 268.1±436.9 mmHg/s,左心室压力下降最大速率(-dp/dtmax):3 008.8±346.7mmHg/s vs.2 536.9±380.4 mmHg/s,P<0.05]。结论自体MSCs移植到兔缺血心肌后可以向心肌细胞分化,提高缺血心肌的心功能,对治疗心肌缺血具有较好的前景。     

肝细胞生长因子及骨髓间充质干细胞联合移植治疗慢性缺血性心脏病的实验研究

目的研究经肝细胞生长因子(HGF)及骨髓间充质干细胞(MSCs)联合移植治疗慢性缺血性心脏病的疗效。方法采集香猪髂骨骨髓,用密度梯度法和贴壁分离法相结合的方法分离、培养MSCs,通过细胞表面标记(CD34、CD44、CD71、Ⅷ因子和desmin)成份鉴定;HGF基因的重组腺病毒(AdHGF)+MSCs共培养并检验HGF对MSCs生物学特征的影响。经左胸冠状动脉回旋支放置Ameroid环建立慢性心肌缺血香猪模型,将40只小型香猪采用随机对照分为5组(n=8),于缺血心肌处分别注射5×106/ml MSCs+4×109pfu 200μl AdHGF(MSCs+AdHGF组)、4×109pfu 200μl AdHGF(AdHGF组)、5×106/ml MSCs 200μl(MSCs组),4×109pfu 200μl AdNull(AdNull组)和生理盐水1 ml(对照组)。治疗4周后行心脏超声心动图,数字减影动脉造影(DSA),单光子发射计算机体层摄影(SPECT)心肌灌注检查及心肌凋亡细胞等检测。结果流式细胞仪检测MSCs表面标记CD44、CD71阳性,CD34、Ⅷ因子、desmin阴性;增殖细胞抗原(PCNA)蛋白表达显示HGF具有较强刺激MSCs增殖分化作用;彩色超声心动图检查提示:经治疗后MSCs+AdHGF组左心室舒张期末容积(LVEDV)、左心室射血分数(LVEF)、短轴缩短率(FS)明显改善,差异有统计学意义(P<0.05);DSA检测缺血区新生血管数MSCs+AdHGF组较AdHGF组、MSCs组明显增多,差异有统计学意义(P<0.05);SPECT显示MSCs+AdHGF组左室心肌增厚、灌注明显改善,运动增强,差异有统计学意义(P<0.05);心肌HE染色血管密度,MSCs+AdHGF组明显高于AdHGF组和MSCs组[(39.4±1.2)个/HPF vs.(36.5±1.4)个/HPF、(34.5±1.7)个/HPF,P<0.05];心肌TUNEL染色法检测,MSCs+AdHGF组、AdHGF组细胞凋亡率明显低于MSCs组(P<0.05)。结论 MSCs+AdHGF联合具有促进慢性缺血心肌新血管生成、抑制细胞凋亡、改善心功能等作用;MSCs+AdHGF联合治疗缺血性心脏病作用较单纯HGF或MSCs移植更明显。     

大网膜联合组织工程心肌移植改善心肌梗死后大鼠心功能

目的 将骨髓间充质干细胞(MSCs)种植于共聚乙交酯-丙交酯(PLGA)补片上构建组织工程心肌(EHT),在大鼠心肌梗死模型上观察大网膜增加EHT血供,改善微环境后对心脏间质胶原重塑及心功能的影响,为心肌梗死的外科治疗提供新的途径. 方法 结扎SD大鼠左冠状动脉,制作心肌梗死模型.以大鼠MSCs为种子细胞构建EHT,将符合心肌梗死标准的18只鼠随机分成3组,每组6只,A组:网膜包裹EHT;B组:单纯EHT移植;对照组:单纯心肌梗死;另设假手术组(n=6):仅开胸,不结扎冠状动脉及EHT移植.EHT植入后4周,用二维超声心动图检测心功能,彩色室壁运动(CK)方法检测梗死部位心室壁运动,取标本做天狼猩红染色在光学显微镜下观察心肌改变. 结果 A组EHT植入后4周部分PLGA纤维降解,梗死部位心肌间质胶原含量较B组和对照组明显减少(P<0.05).CK检查显示A组梗死部位心室壁运动较B组和对照组明显改善(P<0.05);A组左心室收缩期末内径(LVESD)和左心室舒张期末内径(LVEDD)较对照组和B组明显减小(P<0.05),左心室射血分数(LVEF)、左心室缩短分数(LVFS)较对照组和B组明显增大(P<0.05). 结论 大网膜包裹MSCs-PLGA构建的EHT覆盖于梗死心肌表面能改善心肌梗死后间质胶原重塑和梗死部位心室壁运动,有利于心功能的恢复.     

不同剂量的骨髓间充质干细胞移植与改善缺血心脏功能的量效关系

目的探讨不同剂量的骨髓间充质干细胞移植梗死的心肌与改善缺血心脏功能的量效关系。方法结扎F344大鼠的冠状动脉,制作大鼠心肌梗死模型,于模型建立1周后将32只大鼠采用随机数字表法分为4组,每组8只。将经5-溴脱氧尿苷(BrdU)标记的不同剂量的骨髓间充质干细胞,分别为1×103个(组1)、1×105个(组2)、1×107个(组3)注入心肌缺血区;对照组注射等量的无血清IMDM。于模型建立前、细胞移植前和细胞移植后4周采用超声心动图检测射血分数(EF)。细胞移植后4周行BrdU、闰盘连接蛋白(Connexin43)、肌球蛋白重链β(MHC)、平滑肌肌动蛋白α(α-SMA)的免疫组织化学染色。计数α-SMA着色的功能小血管数量。结果细胞移植后4周,组1EF与对照组比较差异无统计学意义(0.34±0.16vs.0.36±0.15,P>0.05),组2EF较组1明显增高(0.54±0.20vs.0.34±0.16,P=0.004),组3EF较组2明显增高(0.71±0.24vs.0.54±0.20,P=0.018)。细胞移植后4周,组2BrdU和MHC双阳性的细胞个数明显多于组1(323.20±91.62个/高倍视野vs.51.75±27.58个/高倍视野,P=0.049),组3的细胞个数明显多于组2(409.75±106.65个/高倍视野vs.323.20±91.62个/高倍视野,P<0.001),对照组为0±0个/高倍视野。组1、组2和组3大部分移植细胞MHC、Connexin43染色呈阳性,心肌缺血区内可见大量α-SMA抗体,部分形态不规则。对照组和组1梗死区域有新生血管形成,组2较组1增多(28.38±12.79个/高倍视野vs.22.75±9.07个/高倍视野,P=0.015),组3较组2增多(35.63±13.27个/高倍视野vs.28.38±12.79个/高倍视野,P=0.002)。结论骨髓间充质干细胞移植能明显改善缺血心脏的功能,且心肌细胞新生和心功能改善的程度均呈现移植细胞剂量依赖性。     

平滑肌细胞移植对心肌梗死后早期心肌基质金属蛋白酶2、9和抑制因子3含量的影响

目的评价平滑肌细胞移植对心肌梗死后早期心肌间质重构的影响。方法选用48只雌性Wistar大鼠,采用随机数字表法分成对照组(n=24)和平滑肌细胞移植组(n=24),经左冠状动脉远端结扎后建立心肌梗死动物模型,立即对梗死区边缘行室壁注射含有1×106个平滑肌细胞或不含细胞的磷酸盐缓冲液(PBS)0.5ml。在移植后1周,通过逆转录-聚合酶链反应(RT-PCR)和免疫杂交观察大鼠心肌内基质金属蛋白酶2、9(MMP-2、MMP-9)和基质金属蛋白酶抑制因子3(TIMP-3)的信使核糖核酸(mRNA)和蛋白变化。结果植入的平滑肌细胞能够存活;平滑肌细胞移植组大鼠缺血区TIMP-3mRNA(1.06±0.22vs.0.81±0.19,t=-2.358,P=0.033)及其蛋白含量(3.33±0.53vs.1.63±0.47,t=-6.802,P0.001)明显高于对照组;平滑肌细胞移植组大鼠缺血区MMP-2、MMP-9mRNA(0.49±0.12vs.1.16±0.18,t=8.453,P0.001;0.45±0.12vs.0.80±0.11,t=5.884,P0.001)及其蛋白含量(3.98±1.08vs.6.05±0.91,t=4.139,P=0.001;0.39±0.14vs.0.57±0.17,t=2.409,P=0.031)明显低于对照组。结论移植的平滑肌细胞可在心肌梗死区及其周围存活,并且增加梗死后心肌中TIMP-3mRNA和蛋白的含量,降低MMP-2、MMP-9mRNA和蛋白含量,抑制心肌不良重构。     

单宁酸缓释微球延缓大鼠心室重构的实验研究

目的探讨单宁酸(tannic acid,TA)缓释微球心肌注射对急性心肌梗死(acute myocardial infarction,AMI)后心室重构的影响。方法制备TA缓释微球,检测其体外释放药物参数。制备大鼠心肌梗死模型,将80只大鼠按随机数字表法分为空白微球组[聚乳酸-羟基乙酸共聚物(PLGA)组,n=24]、TA缓释微球(PLGA-TA)组(n=24)、TA组(n=16)和生理盐水(NS)组(n=16)。术后用超声心动图评价心功能;术后4周,观察心肌梗死边缘组织的心肌细胞外基质(ECM)排列;术后2周和4周,测定心肌梗死区胶原蛋白含量。结果 TA持续从微球载体中释放1个月。术后2周PLGA-TA组、TA组的左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)、左心室舒张期末内径(LVEDD)和左心室收缩期末内径(LVESD)指标均明显优于其它两组(P<0.05);术后4周,PLGA-TA组的LVEF、LVFS、LVEDD、LVESD指标均明显优于其它3组(P<0.05)。术后4周PLGA-TA组心肌ECM排列较TA组更为有序整齐。术后4周PLGA-TA组的心肌梗死区胶原蛋白含量高于TA组[(88.88±7.28)μg/mg心肌干重vs.(72.43±9.02)μg/mg心肌干重]、PLGA组[(88.88±7.28)μg/mg心肌干重vs(.71.97±6.06)μg/mg心肌干重]和NS组[(88.88±7.28)μg/mg心肌干重vs.(68.86±7.55)μg/mg心肌干重],差异有统计学意义(F=7.162,P=0.003);而TA组、PLGA组、NS组之间比较差异无统计学意义(P>0.05)。结论 TA缓释微球心肌注射可较长时间遏制AMI后ECM的降解,有效延缓心室重构的发生。     

骨髓间充质干细胞移植重建大鼠缺血心肌的实验研究

目的　探讨大鼠骨髓间充质干细胞 (MSCs)移植于缺血心肌后的增殖分化情况和对缺血心肌细胞的修复重建能力及心功能改善情况。　方法　实验组为将体外培养SD大鼠的MSCs经溴氮胞苷 (BrdU)标记后显微注射于结扎冠状动脉后的大鼠缺血心肌内 ,并以无血清培养基注射动物为对照组。 4周后观察移植细胞的分化情况 ,并通过超声多普勒、心肌核素显像、免疫组化和新生血管形成情况来检测心功能变化。　结果　实验组MSCs移植 4周后 ,在缺血心肌区内可发现不同分化阶段的心肌样细胞。超声检查发现实验组的左室射血分数 (LVEF)的改善明显好于对照组 (P <0 0 5 ) ;SPECT显示实验组心肌核素摄取显著高于对照组 (P <0 0 1) ;在促新生血管形成方面 ,实验组也明显好于对照组(P <0 0 5 )。　结论　骨髓间充质干细胞移植于缺血心肌后可重建缺血心肌 ,增加心肌灌注 ,显著改善心功能。     

转基因的骨髓间充质干细胞治疗大鼠缺血皮瓣

目的探讨转染血管内皮细胞生长因子(VEGF)基因的大鼠骨髓间充质干细胞(MSCs)同种异体移植促进缺血皮瓣的血管新生,从而提高皮瓣存活率的可能性。方法体外分离、培养、鉴定SD大鼠MSCs,PcDNA3.1(-)/VEGF165质粒转染MSCs,免疫荧光方法检测MSCs体外表达VEGF的情况,CM-DiI标记MSCs。SD大鼠随机分3组:A组[PcDNA3.1(-)/VEGF165质粒转染的MSCs移植]、B组(单纯MSCs移植)、C组(DMEM-F12培养基)。每只大鼠背侧皮下按组分别注射细胞悬液和培养基,注射后ELISA法连续检测大鼠血浆VEGF浓度,注射后第4天掀起1个蒂在尾侧的9 cm×2 cm的随意皮瓣。在术后第14天分别观察皮瓣的存活率、激光多普勒血液监测仪监测血流灌注、CD34免疫组织化学检测皮瓣毛细血管密度、荧光显微镜检测MSCs在皮瓣内的分布和存活状况。结果转染VEGF165基因的MSCs体外和体内检测均高表达VEGF165蛋白。A、B、C三组的皮瓣存活率分别为(83.1±2.6)%、(66.4±6.1)%、(51.5±7.5)%(P< 0.05);A、B、C三组的毛细血管密度(条/mm2)分别为:89.2±6.1、57.1±4.7、28.7±2.8(P< 0.05);血流灌注比值A组高于B、C两组,B组高于C组(P<0.05);转染VEGF165基因的MSCs移植SD大鼠皮瓣后,MSCs存活并参与血管新生。结论转染VEGF基因的大鼠MSCs体外培养后异体移植可促进缺血皮瓣的血管新生,提高存活率。     

心肌缺血期肢体缺血处理对大鼠心肌的保护作用

目的 观察心肌缺血期肢体缺血处理是否具有心肌保护作用.方法 将24只成年雄性Wistar大鼠随机分为心肌缺血/再灌注组(IR组)、假手术组(S组)、缺血期肢体缺血处理组(RP组).经胸骨下段切口建立大鼠心肌缺血再灌注损伤(IRI)模型,监测心电、左心室压力,比较心律失常评分、左心室压力变化率、左心室压峰值及血清磷酸肌酸激酶(CK)和心肌肌钙蛋白T(c-TNT)等.结果 再灌注早期RP组心律失常评分为(1.50±0.97),与IR组(2.33±0.71)差异有统计学意义(P<0.05);RP组的左心室压峰值及变化率均介于S组与IR组之间,但与IR组的差异无统计学意义(P>0.05).3组间CK差异无统计学意义(P>0.05),IR组与S组的c-TNT差异有统计学意义(P<0.05),但RP与IR及S组间差异均无统计学意义(P>0.05).结论 大鼠心肌缺血期肢体缺血处理具有一定的心肌保护作用,主要表现为减轻再灌注性心律失常.     

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.