不同品系大鼠之间肝移植排斥反应的比较研究

目的比较不同品系大鼠之间肝移植排斥反应特点。方法依据大鼠不同品系分成对照组SD→SD(A组),实验组Wistar→SD(B组)、Lewis→BN(C组)以及DA→Lewis(D组)4个组,采用Kamada双袖套法建立大鼠原位肝移植模型。比较各组受体大鼠术后10 d血清肝功能指标[丙氨酸转氨酶(ALT)、总胆红素(TB)和白蛋白(Alb)]、血清白细胞介素(IL)-2和IL-10水平、急性排斥反应组织病理学分级和术后平均生存时间。结果与A、B组比较,C组和D组的血清ALT和TB明显升高,Alb明显降低,差异均有统计学意义(均为P0.05)。与C组比较,D组的TB明显升高,Alb明显降低,差异均有统计学意义(均为P0.05)。与A组比较,B、C、D组大鼠血清IL-2和IL-10水平均明显升高,C组和D组的IL-2/IL-10亦明显升高,差异有统计学意义(均为P0.05)。与B组比较,C组和D组大鼠血清IL-2水平明显升高,D组的IL-2/IL-10亦明显升高,差异有统计学意义(均为P0.05)。与C组比较,D组大鼠血清IL-2水平明显升高,D组的IL-2/IL-10亦明显升高,差异有统计学意义(均为P0.05)。肝组织病理学检查显示,A组大鼠肝组织未见明显排斥反应,排斥活动性指数(RAI)评分(1.8±0.7)分;B组RAI评分(3.1±1.3)分,属轻度或不明确性排斥反应;C组RAI评分(6.9±0.8)分,属中~重度排斥反应;D组RAI评分(8.8±0.5)分,属重度排斥反应。各组间RAI评分比较以及组间两两比较,差异均有统计学意义(均为P0.05)。A组、B组、C组、D组受体大鼠术后平均生存时间分别为(119.3±1.9)d、(116.9±8.3)d、(53.4±6.1)d、(12.1±2.4)d,A组与B组的生存时间比较差异无统计学意义,余各组两两比较差异均有统计学意义(均为P0.05)。结论 4种组合中,大鼠DA→Lewis模型排斥反应最剧烈,Lewis→BN次之,而Wistar→SD最轻,接近于免疫耐受。     

槐耳清膏在小鼠心脏移植排斥反应中作用的初步探讨

目的 探讨槐耳清膏在小鼠心脏移植急性排斥反应中的作用.方法 实验分为3组:A组:同种异基因移植后槐耳清膏处理组(槐耳清膏组);B组:同种异基因移植财照组(移植排斥组)及C组:同系移植对照组(同系移植组).观察各组移植心脏的存活时间、术后第5天供心的组织病理改变.用免疫荧光检测移植心脏中CD8+T淋巴细胞的浸润和颗粒酶B的表达水平.结果 A组移植心脏的平均存活时间为(6.38±0.69)d,与B组(8.31±0.59)d相比明显缩短(P<0.01);心肌组织呈3级急性排斥反应病理改变,CD8+T淋巴细胞弥漫性浸润及颗粒酶B表达与两个对照组相比明显增强(P<0.05).结论 在术后早期单用槐耳清音会促进小鼠心脏移植物的急性排斥反应,可能机制足促进CD8+T淋巴细胞的组织浸润并增强颗粒酶B的表达.     

白细胞靶向心肌超声造影技术评价心脏移植后急性排斥反应的研究

目的 探讨白细胞靶向心肌超声造影技术对心脏移植术后急性排斥反应及其程度的诊断价值.方法 将实验大鼠随机分为4组,行腹腔异位心脏移植术.A组为同系移植,供、受者均采用健康雄性SD大鼠;B、C、D组为同种移植,供者采用健康雄性SD大鼠,受者采用健康雄性Wistar大鼠.B、C组分别于移植前3 d起每天腹腔注射环孢素A(CsA)10 mg·kg-1·d-1和3 mg·kg-1·d-1,A、D组不给予CsA治疗.每组抽取成功建立腹部异位心脏移植模型的受者各8只.术后第3天,将声诺维造影剂经颈内静脉持续注入大鼠体内,应用心肌超声造影技术观察移植心脏,分别获取注入造影剂20 s时的心肌灌注造影图像和5 min时的白细胞靶向心肌造影图像,利用图像分析仪分别测定每只受者的造影图像灰阶值(GS20s、GS5m)和靶向灰阶值(Gstarget,为GS5m与GS20s之差).造影观察完毕后处死大鼠,行病理学检查,HE染色确定移植心肌排斥反应程度;免疫组织化学法检测移植心肌组织内CD3+T淋巴细胞浸润程度,并将其分别与各组的GS20s、GS5m和Gstatget做相关性分析.结果 心肌灌注造影显示各组GS20s之间无明显差异(P＞0.05);白细胞靶向造影显示各组GS5m之间存在梯度,差异有统计学意义(P＜0.05);且各组Gstarget之间的差异也有统计学意义(P＜0.01).移植心肌组织病理学检测显示:A组为0～Ⅰ级排斥反应,B组为Ⅰ～Ⅱ级排斥反应,C组为Ⅱ～Ⅲ级排斥反应,D组为Ⅲ～Ⅳ级排斥反应.免疫组织化学检测显示:从A组到D组,移植心肌组织中CD3+T淋巴细胞计数逐渐增多.相关性分析显示:CD3+T淋巴细胞计数与Gstarget呈正相关(r=0.86,P＜0.001),与GS5m有相关性,与GS20s无相关性.结论 白细胞靶向心肌超声造影技术能无创、有效的评价心脏移植术后的急性排斥反应程度.     

移植物浸润T淋巴细胞肿瘤坏死因子相关凋亡诱导配体及受体DR4和DR5表达与大鼠小肠移植急性排斥反应的相关性

目的 探讨浸润T淋巴细胞七的DR4、DR5表达同小肠移植急性排斥反应的关系.方法 将2种近交系大鼠(SD、Wistar)54只按随机配对法分为A、B、C3组.A组大鼠为对照组(18只)行虚拟手术;B组(18只)大鼠行同系小肠移植;C组(18只)大鼠行不同品系小肠移植.各组大鼠于术后5 d取移植肠样本分别做HE染色和免疫荧光双标记染色.采用免疫荧光染色、激光共聚焦技术测定各组标本浸润T淋巴细胞肿瘤坏死因相关凋亡诱导配体及DR4、DR5的表达情况.结果 A组大鼠小肠黏膜正常,B组大鼠小肠表现为免疫耐受,C组大鼠表现为急性排斥反应.C组大鼠高T淋巴细胞表达肿瘤坏死因子相关凋亡诱导配体与A、B组大鼠比较差异有统计学意义(P < 0.01);A、B组大鼠浸润T淋巴细胞DR4、DR5均呈高表达,C组大鼠呈低表达,C组大鼠与A、B组比较差异有统计学意义(P < 0.01);A、B组大鼠比较差异无统计学意义(P > 0.05).结论 急性排斥反应的发生可能与浸润T淋巴细胞DR的低表达有关.减少浸润淋巴细胞DR表达的下调,或者上调DR将有助于控制急性排斥反应,诱导免疫耐受.     

移植物浸润T淋巴细胞肿瘤坏死因子相关凋亡诱导配体及受体DR4和DR5表达与大鼠小肠移植急性排斥反应的相关性

目的 探讨浸润T淋巴细胞七的DR4、DR5表达同小肠移植急性排斥反应的关系.方法 将2种近交系大鼠(SD、Wistar)54只按随机配对法分为A、B、C3组.A组大鼠为对照组(18只)行虚拟手术;B组(18只)大鼠行同系小肠移植;C组(18只)大鼠行不同品系小肠移植.各组大鼠于术后5 d取移植肠样本分别做HE染色和免疫荧光双标记染色.采用免疫荧光染色、激光共聚焦技术测定各组标本浸润T淋巴细胞肿瘤坏死因相关凋亡诱导配体及DR4、DR5的表达情况.结果 A组大鼠小肠黏膜正常,B组大鼠小肠表现为免疫耐受,C组大鼠表现为急性排斥反应.C组大鼠高T淋巴细胞表达肿瘤坏死因子相关凋亡诱导配体与A、B组大鼠比较差异有统计学意义(P < 0.01);A、B组大鼠浸润T淋巴细胞DR4、DR5均呈高表达,C组大鼠呈低表达,C组大鼠与A、B组比较差异有统计学意义(P < 0.01);A、B组大鼠比较差异无统计学意义(P > 0.05).结论 急性排斥反应的发生可能与浸润T淋巴细胞DR的低表达有关.减少浸润淋巴细胞DR表达的下调,或者上调DR将有助于控制急性排斥反应,诱导免疫耐受.     

移植物浸润T淋巴细胞肿瘤坏死因子相关凋亡诱导配体及受体DR4和DR5表达与大鼠小肠移植急性排斥反应的相关性

目的 探讨浸润T淋巴细胞七的DR4、DR5表达同小肠移植急性排斥反应的关系.方法 将2种近交系大鼠(SD、Wistar)54只按随机配对法分为A、B、C3组.A组大鼠为对照组(18只)行虚拟手术;B组(18只)大鼠行同系小肠移植;C组(18只)大鼠行不同品系小肠移植.各组大鼠于术后5 d取移植肠样本分别做HE染色和免疫荧光双标记染色.采用免疫荧光染色、激光共聚焦技术测定各组标本浸润T淋巴细胞肿瘤坏死因相关凋亡诱导配体及DR4、DR5的表达情况.结果 A组大鼠小肠黏膜正常,B组大鼠小肠表现为免疫耐受,C组大鼠表现为急性排斥反应.C组大鼠高T淋巴细胞表达肿瘤坏死因子相关凋亡诱导配体与A、B组大鼠比较差异有统计学意义(P < 0.01);A、B组大鼠浸润T淋巴细胞DR4、DR5均呈高表达,C组大鼠呈低表达,C组大鼠与A、B组比较差异有统计学意义(P < 0.01);A、B组大鼠比较差异无统计学意义(P > 0.05).结论 急性排斥反应的发生可能与浸润T淋巴细胞DR的低表达有关.减少浸润淋巴细胞DR表达的下调,或者上调DR将有助于控制急性排斥反应,诱导免疫耐受.     

大鼠肝移植急性排斥反应的淋巴细胞蛋白质组学研究

目的 利用差异蛋白质学寻找肝移植急性免疫排斥反应相关功能蛋白.方法 选取SD大鼠与Wistar大鼠,建立大鼠同种异体肝移植的动物模型(急性排斥组)和大鼠同基因移植的动物模型(对照组);使用组织化学方法 对移植肝脏进行形态学观察;利用ELISA检测受体血清细胞因子;通过双向凝胶电泳分离急性排斥组和对照组肝移植后受体大鼠脾脏的淋巴细胞蛋白质,通过软件比较两组蛋白质的质纹图谱,进行差异点分析;选取差异点用基质辅助激光解析-飞行时间质谱进行蛋白鉴定;选取部分鉴定蛋白通过Western blot法进行检测,验证蛋白质组学的分析结果 .结果 ELISA检测结果 表明,移植术后3 d同种异体肝移植大鼠血清中IL-2和IFN-γ的表达上调;急性排斥组肝组织HE染色切片证实均有Ⅱ a～Ⅱ b级(Banff标准)排斥反应表现;差异蛋白质组学分析共鉴定出25个淋巴细胞蛋白质在急性排斥反应中的表达量发生了改变,其中13个蛋白点表达上调,12个蛋白点表达下调;Western blot法验证结果 显示,其中的2个相关蛋白(β-actin和碳酸酐酶)在急性排斥反应中的表达量变化与差异蛋白质组学分析结果 一致.结论 本实验筛选出25个大鼠肝移植急性排斥反应的相关功能蛋白,其中的β-actin和碳酸酐酶在排斥反应中有重要功能,为进一步系统研究这一免疫学现象奠定了基础.     

ClC-3在大鼠异位心脏移植急性排斥期的表达及意义

目的观察电压门控氯通道-3(C lC-3)在大鼠异位心脏移植急性排斥期中的表达及意义。方法以SD大鼠为供者,W istar大鼠为受者,建立大鼠腹部心脏异位移植模型,分为两组,每组32对。对照组:用生理盐水灌胃;环孢菌素A(C sA)组:用C sA灌胃干预。每组8只观察移植心存活时间,术后1、3、5和7d各切取6只标本,常规组织切片监测排斥反应,以原位末端标记(TUNEL)法检测心肌细胞凋亡,逆转录-聚合酶链反应(RT-PCR)检测移植心肌组织C lC-3的表达。结果C sA组移植心存活时间明显长于对照组(15.4±5.1d vs.7.6±1.5d,P<0.05);C sA组各采样时段的免疫排斥反应分级及心肌凋亡指数明显低于对照组(P<0.05),而C lC-3表达强度均强于对照组(P<0.05)。C sA干预能明显降低免疫排斥反应分级及心肌凋亡指数,改善C lC-3表达强度的降低。结论移植心脏中C lC-3表达水平的高低与心脏急性免疫排斥反应的轻重及心肌细胞凋亡指数的高低密切相关,提示C lC-3在移植心脏免疫排斥反应心肌细胞凋亡坏死中有着重要的作用。     

紫杉醇对大鼠心脏移植物急性排斥反应的免疫抑制作用

目的探讨紫杉醇对大鼠心脏移植后急性排斥反应的免疫抑制作用。方法以W istar大鼠为供者,SD大鼠为受者,建立大鼠腹腔异位心脏移植模型。70只SD大鼠随机分为5组,每组14只。对照组:术后不使用免疫抑制药;组Ⅰ:术后腹部注射紫杉醇(0.75 m g/kg.d);组Ⅱ:术后腹部注射紫杉醇(1.5 m g/kg.d);组Ⅲ:术后给环孢菌素A(C sA,5m g/kg.d)灌胃;组Ⅳ:术后腹部注射紫杉醇(0.75 m g/kg.d)+C sA(5m g/kg.d)灌胃。观察5组大鼠一般情况、移植心脏存活时间及术后7d病理学改变。结果组Ⅰ、组Ⅱ、组Ⅲ和组Ⅳ大鼠移植心脏存活时间均较对照组显著延长(P<0.05),组Ⅳ存活时间长于组Ⅰ和组Ⅲ(P<0.05)。术后第7d,对照组移植心脏明显肿胀,病理急性排斥反应分级为3级以上。组Ⅰ和组Ⅱ移植心脏搏动有力,颜色鲜红、质软,病理急性排斥反应分级为2~3级,与对照组比较,能明显减轻移植后心肌病理损害(P<0.05)。组Ⅲ移植心脏搏动良好,急性排斥反应分级大部分为2级。组Ⅳ移植心脏大小基本正常,无水肿,颜色鲜红、质软,搏动好,病理急性排斥反应分级<2级;对移植心心肌保护作用优于组Ⅰ和组Ⅱ(P<0.05)。结论紫杉醇能减轻大鼠心脏移植术后急性排斥反应,并能延长移植心脏的存活时间,具有免疫抑制作用。小剂量紫杉醇与C sA联用,在抗心脏移植物排斥反应中具有协同作用。     

血小板源性生长因子A在大鼠移植心脏血管病变及纤维化中的作用

目的 探讨血小板源性生长因子A(PDGF-A)在移植心脏血管病变及心肌纤维化中的作用.方法 选择近交系健康雄性Wistar大鼠及SD大鼠,建立大鼠异位心脏移植模型.实验分为四组,每组8只.正常对照组:取正常Wistar大鼠的心脏作为空白对照.无排斥组:心脏移植的供、受者均为Wistar大鼠,移植后第60天取移植心脏.急性排斥组和慢性排斥组:心脏移植的供者均为Wistar大鼠,受者均为SD大鼠;急性排斥组术后未行免疫抑制治疗,术后第5天取移植心脏;慢性排斥组术后给予环孢素A 10 mg·kg-1·d-1,皮下注射,移植后第60天取移植心脏.采用免疫组织化学染色法检测移植心脏的巨噬细胞浸润(CD68阳性细胞数)情况;逆转录聚合酶链反应(RT-PCR)分析PDGF-A mRNA的表达水平.结果 正常对照组和无排斥组未见巨噬细胞浸润;急性排斥组巨噬细胞浸润主要见于心肌及冠状血管周围;慢性排斥组巨噬细胞浸润见于心肌及血管周围,在心肌坏死纤维化较严重的区域,巨噬细胞浸润尤为明显;正常对照组、无排斥组、急性排斥组和慢性排斥组移植心组织中PDGF-A mRNA的相对表达量分别为:0.26±0.06、0.31±0.04、0.88±0.12和0.94±0.11,慢性排斥组和急性排斥组中PDGF-A mRNA的相对表达量明显高于正常对照组和无排斥组(P＜0.01).结论 巨噬细胞浸润及血小板源性生长因子表达水平与移植心脏血管病变及心肌纤维化有关.     

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.     

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.     

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.     

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.     

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.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.