肾移植受者血他克莫司浓度对外周血自然杀伤细胞及其受体的影响

目的 研究肾移植受者血他克莫司(Tac)浓度对外周血自然杀伤(NK)细胞及其受体的影响.方法 将2007年12月至2009年7月间的60例受者纳入研究,术后受者均采用以Tac为基础的免疫抑制方案.根据术后6个月监测到的血Tac浓度将受者分为低浓度组和高浓度组[各为30例,术后6个月时血Tac浓度分别为(6.84±1.72)和(11.88±2.59)μg/L],另以20名健康志愿者作为对照组.术前和术后6个月,采用流式细胞术检测NK细胞及其抑制性受体(CD85j和CD158d)和活化性受体( CD94、NKG2D)的表达情况,采用酶联免疫吸附试验法检测免疫耐受分子分泌型HLA-G5( sH LA-G5)的表达水平.结果 术前低浓度组和高浓度组受者外周血NK细胞绝对值均较对照组显著降低(P＜0.05),术后6个月时低浓度组和高浓度组NK细胞比例及绝对值较对照组均显著降低(P＜0.05),低浓度组NK细胞绝对值显著高于高浓度组(P＜0.05).术前两组间CD85j、CD158d、CD94、NKG2D表达的差异均无统计学意义(P＞0.05);术后6个月时低浓度组和高浓度组CD85j和CD158d的表达较术前升高,CD94和NKG2D的表达下降,而低浓度组CD85j和CD158d的表达显著高于高浓度组(P＜0.05).经Spearman系数统计,CD85j和CD158d与sHLA-G5呈正相关(P＜0.01),NKG2D与sHLA-G5呈负相关(P＜0.01).结论 肾移植受者血Tac浓度与外周血NK细胞数量及其受体的表达具有相关性,低血Tac浓度受者的NK细胞数量及其抑制性受体的表达升高,仍然能有效保护移植肾功能.     

复发性流产患者主动免疫治疗后淋巴细胞免疫表型的变化

目的探讨原因不明复发性流产(URSA)患者行淋巴细胞主动免疫治疗(LIT)后淋巴细胞免疫表型的变化对治疗效果的评估价值。方法采用流式细胞术分析URSA患者LIT前后外周血T淋巴细胞、B淋巴细胞、NK细胞和调节性T细胞免疫表型的变化(P0.05)。结果 25例URSA患者经LIT后成功妊娠16例,治疗后所有URSA患者(n=25)和妊娠成功组(n=16)外周血CD3+T细胞、CD4+HLA-DR+T细胞比例较治疗前均明显增加,CD4+T和CD3-CD56+NK细胞比例明显降低(P0.05);而治疗前后B细胞和Treg细胞、CD56bright CD16-NK、CD56dimCD16+NK、CD3+CD56+NKT及CD69+NK细胞比例则无明显变化(P0.05)。结论 LIT后外周血T细胞、NK细胞的比例发生了明显变化,CD4+T细胞、CD3-CD56+NK细胞比例降低和CD3+T细胞、活化CD4+T细胞增加也许有利于维持妊娠,T细胞和NK细胞的免疫表型有望作为LIT疗效评估的一个重要指标。     

流式细胞术在肾移植术后感染中的诊断价值

目的探讨流式细胞术在肾移植术后感染中的诊断价值。方法根据术后影像学和实验室检查结果,将51例首次肾移植受体分为细菌组33例、真菌组9例、BK病毒组9例;另选择肾移植术后稳定的受体28例作为稳定组。采用流式细胞术分析各组受体外周血淋巴细胞亚群比例和绝对计数。比较各组肾移植受体的肾功能、外周血淋巴细胞亚群的比例及绝对计数;采用受试者工作特征(ROC)曲线分析淋巴细胞亚群比例和绝对计数在肾移植术后感染性疾病中的诊断价值。结果与稳定组相比,细菌组、真菌组和BK病毒组血清肌酐(Scr)水平和血尿素氮(BUN)水平均有不同程度升高,差异均有统计学意义(P=0.035、0.007、0.024;0.037、0.006、0.032)。与稳定组比较,细菌组和真菌组CD16+CD56+自然杀伤(NK)细胞比例均下降(P=0.036、0.015);真菌组CD4+/CD8+T细胞比例明显下降(P=0.004)。与细菌组相比,真菌组和BK病毒组的CD3+CD8+T细胞比例均升高(P=0.013、0.008),CD3+CD4+T细胞比例均降低(P=0.003、0.010),CD4+/CD8+T细胞比例均明显下降(P=0.003、0.005)。与稳定组比较,细菌组、真菌组、BK病毒组CD3+T细胞数量、CD3+CD8+T细胞数量、CD16+CD56+NK细胞数量均明显降低(P=0.025、0.002、0.003;0.015、0.005、0.006;0.001、0.001、0.031);真菌组和BK病毒组CD3+CD4+T细胞数量降低(P=0.001、0.003);BK病毒组CD19+B细胞数量明显降低(P=0.019)。与细菌组比较,真菌组CD3+CD4+T细胞数量明显降低(P=0.023)。ROC曲线分析显示,CD3+CD4+T细胞和CD16+CD56+NK细胞数量诊断真菌感染的准确度较高,ROC曲线下面积分别为0.8492和0.8889;CD3+T细胞、CD3+CD4+T细胞和CD19+B细胞数量诊断BK病毒感染的准确度较高,ROC曲线下面积分别为0.8472、0.8452和0.8115。结论采用流式细胞术检测外周血淋巴细胞亚群可以评估患者机体免疫功能状态,绝对计数能够直观地判断免疫程度,两者结合对于肾移植受者感染性疾病的诊断和鉴别诊断具有指导意义。     

全身照射预处理供体对异基因大鼠肝移植的作用及对受体内CD4~+CD25~+调节性T细胞的影响

目的 探讨全身照射(TBI)预处理诱导大鼠肝移植术后急性排斥反应的发生机制,及CD4~+ CD25~+调节性T细胞的变化在诱导免疫耐受中的作用.方法 以雄性Lewis、DA大鼠为供、受体,随机分为正常对照组、同种肝移植组、自发免疫耐受组、急性排斥反应组.观察各组受体的生存时间及生存率,检测受体术后外周血中ALT、TB含量、Foxp3~+ CD4~+ CD25~+ 调节性T细胞和T细胞亚群上GITR的表达,检测受体术后第14天移植肝的病理变化和受体脾脏CTL杀伤活性.结果 自发免疫耐受组,术后经历短暂排斥反应最终获得免疫耐受并长期存活.急性排斥反应组,在术后第17～21天死亡,与其他组相比,外周血血清中ALT、TB含量明显升高,而Foxp3~+ CD4~+ CD25~+调节性T细胞比例明显降低.TBI预处理大鼠供肝致受体外周血中CD3~+ CD4~+ T细胞上GITR表达降低,CD3~+CD8~+T细胞上GITR表达增加,提高CTL的杀伤活性.结论 通过TBI清除供体大鼠肝移植物中携带的旁路淋巴细胞,致受体外周血中Foxp3~+ CD4~+ CD25~+调节性T细胞表达降低,而使CD3~+ CD8~+T细胞上GITR表达增加,共同诱导大鼠肝移植术后急性排斥反应发生和耐受障碍.     

外周血淋巴细胞亚群绝对值和功能的动态监测在肾移植术后早期病毒感染风险预测中的价值

目的探讨不同淋巴细胞亚群的绝对值和功能对于评估肾移植受者术后早期发生病毒感染风险的预测和诊断价值。方法将95例肾移植受者纳入前瞻性观察队列研究,根据术后的免疫状态分为稳定组(77例)和感染组(18例)。分别于术前、术后2周、术后1个月、术后2个月、术后6个月采集外周血样本进行流式细胞检测。比较两组CD4⁺T细胞、CD8⁺T细胞、自然杀伤(NK)细胞绝对值的动态变化,通过检测干扰素(IFN)-γ⁺CD4⁺T细胞、IFN-γ⁺CD8⁺T细胞、IFN-γ⁺NK细胞比例分析两组受者淋巴细胞亚群功能,评估淋巴细胞亚群绝对值和功能在肾移植术后早期对病毒感染的预测和诊断价值。结果在病毒感染时,感染组的CD4⁺T细胞、CD8⁺T细胞、NK细胞绝对值整体处于相对较低的水平;在术后2个月时,感染组的CD4⁺T细胞、NK细胞绝对值均低于稳定组;在术后6个月时,感染组的CD4⁺T细胞、CD8⁺T细胞绝对值均低于稳定组(均为P<0.05)。在病毒感染时,感染组的IFN-γ⁺CD4⁺T细胞、IFN-γ⁺CD8⁺T细胞、IFN-γ⁺NK细胞比例均处于相对较低的水平,尤以IFN-γ⁺CD8⁺T细胞比例降低最为显著;在术后2个月,感染组的IFN-γ⁺CD8⁺T细胞、IFN-γ⁺NK细胞比例显著高于稳定组;在术后6个月,感染组的IFN-γ⁺CD4⁺T细胞、IFN-γ⁺CD8⁺T细胞比例均高于稳定组(均为P<0.05)。logistic回归分析结果显示,术后2个月时,IFN-γ⁺CD8⁺T细胞和IFN-γ⁺NK细胞比例的升高与病毒感染风险增加均相关(均为P<0.05)。受试者工作特征(ROC)曲线结果表明,淋巴细胞亚群绝对值联合其IFN-γ分泌功能对于免疫状态低下的受者病毒感染的诊断价值显著高于单用淋巴细胞亚群绝对值(P<0.05)。结论动态监测淋巴细胞亚群绝对值和功能的变化对病毒感染的预测、诊断及指导用药具有重要参考价值。     

同种异体肾移植后CD4+、CD8+、CD16+、CD19+、CD56+变化及临床意义

目的了解对比肾移植受者术后体内淋巴细胞免疫表型的变化情况及其临床意义.方法采用多种单克隆抗体及流式细胞仪,对肾移植受者术后的淋巴细胞免疫表型进行了化验监测,分析了淋巴细胞免疫表型变化与免疫用药及并发症的关系.结果移植受者淋巴细胞免疫表型阳性细胞数普遍偏低(P＜0.05),肾移植后顺利恢复组的淋巴细胞免疫表型阳性细胞与健康对照组无差异(P＞0.05),肾移植后并发症组受者CD4+、CD8+阳性细胞数低于临床正常值,NK细胞及CD19+阳性细胞数减少(P＜0.05).肾移植后急排组的NK细胞及CD19+阳性细胞数明显增加,CD4+/CD8+比值偏高(P＜0.05).结论淋巴细胞免疫表型可用于评价移植受者的免疫状态,临床上根据受者的化验结果综合评价受者的免疫抑制状态,并作为调整免疫抑制剂用量的参考指标.     

腹膜透析和血液透析对终末期肾病患者免疫功能的对比研究

目的:探讨腹膜透析和血液透析对终末期肾病患者NK细胞和T细胞亚群的影响。方法:选取2010年6月~2014年3月我院收治的126例终末期肾病患者作为研究对象,按照治疗方法将患者随机分为腹膜透析组和血液透析组。腹膜透析组患者行非卧床持续性腹膜透析,血液透析组行常规血液透析。分别于透析前和透析后6个月采集静脉血,采用流式细胞术对两组患者血液中CD+3CD4、CD+3CD+8T淋巴细胞比例、CD4/CD8比值、调节性T细胞比例以及NK细胞的比例比较分析。采用MTT法检测NK细胞的活性。结果:腹膜透析组和血液透析组患者治疗前CD+3CD4、CD+3CD+8、CD4/CD8比值、调节性T细胞比例以及NK细胞的比例及活性比较差异无统计学意义(P0.05)。两组治疗后CD+3CD4T淋巴细胞比例、CD4/CD8比值、Treg细胞比例、NK细胞比例及活性较治疗前显著下降,而CD+3CD+8T淋巴细胞比例无变化(P0.05)。血液透析组患者治疗后外周血中CD+3CD4T淋巴细胞比例、CD4/CD8比值、Treg细胞比例、NK细胞比例及活性下降较腹膜透析组更为显著(P0.05)。两组治疗后组内CD+3CD+8T淋巴细胞水平比较差异无统计学意义(P0.05)。结论:腹膜透析和血液透析会导致患者免疫系统功能低下,其中血液透析对患者免疫系统影响更大。     

氟比洛芬酯联合吗啡镇痛对胃癌患者T淋巴细胞亚群及自然杀伤细胞的影响

目的 观察氟比洛芬酯联合吗啡镇痛对胃癌根治术患者罔术期外周血T淋巴细胞亚群及自然杀伤(NK)细胞的影响.方法 40例择期全麻下行胃癌根治术患者随机分为氟比洛芬酯组(A组)和吗啡组(B组),每组20例,分别于术前0.5 h静注氟比洛芬酯或安慰药英脱利匹特,术后距第一次给药6 h再次静注氟比洛芬酯或英脱利匹特.两组患者术后均行患者自控静脉镇痛(PCIA).于麻醉前、手术开始后2 h、术后24、48、120 h五个时点用流式细胞仪检测T淋巴细胞亚群(CD3+、CD4+、CD8+)及NK细胞(CD3+CD6+CD56+).结果 与麻醉前比较,两组CD3+、CD4+、CD4+/CD8+和NK细胞在手术2 h、术后24、48 h均明显降低(P<0.05);术后120 h CD3+CD16+CD56+仍未恢复至麻醉前水平(P<0.05).与B组比较,A组CD3+、CD4+、CD4+/CD8+在术后24 h下降幅度较小(P<0.05),而NK细胞则在手术2 h和术后24 h下降幅度较小(P<0.05).结论 胃癌根治术患者围术期用氟比洛芬酯联合吗啡镇痛较单用吗啡镇痛对T淋巴细胞亚群和NK细胞有保护作用.     

射频消融治疗脾功能亢进症对机体细胞免疫功能的影响

目的 探索射频消融治疗肝硬化门静脉高压性脾功能亢进症的近远期疗效以及其对机体细胞免疫功能的影响.方法 使用随机分组的方法 将符合纳入标准的43例患者分为射频治疗组(22例)和手术对照组(21例).两组患者分别于术前和术后1周、1个月、6个月、1年、2年、3年时采静脉血进行血常规、淋巴细胞转化率、NK细胞活性和淋巴细胞亚群的测定,使用t检验对组间差异进行对比分析. 结果 两组患者脾亢症状均得到较好的缓解.射频治疗组各项细胞免疫指标手术前后无明显差别;手术对照组术后NK细胞活性和T淋巴细胞转化率均明显低于术前水平(P值均小于0.05),与射频治疗组差异亦非常显著.虽然随着术后时间的延长,其NK细胞活性和T淋巴细胞转化率呈现一定的上升趋势,但是仍与术前水平有显著下降.手术对照组CD4+T细胞及CD4+/CD8+比值较术前有显著降低(P值均小于0.05),但是随着术后时间延长其表现出逐渐恢复的趋势,其中CD4+T细胞和CD4+/CD8+比值分别在术后30个月(P=0.078)和术后36个月(P=0.103)时恢复至术前水平.结论 RFA治疗脾亢在较好的缓解患者脾亢症状的同时由于保留了部分脾脏组织从而较好的保留了机体的细胞免疫功能,且具有创伤小,易操作,并发症少的优点,值得在临床上推广应用.     

微波定量消融脾组织治疗脾大脾亢对患者免疫功能的影响

目的 探讨脾大、脾亢微渡部分消融脾脏组织对机体免疫功能的影响.方法 对脾大、脾亢患者在腹腔镜下或超声引导下经皮行脾组织微波定量消融治疗,治疗前、后分别检测患者外周血T淋巴细胞亚群、B淋巴细胞及NK细胞.结果 治疗后1个月外周血T淋巴细胞亚群CD3、CD4+细胞水平明显升高.B细胞水平每个检测时间点均较治疗前明显升高.脾脏微波消融体积≤20%组CD3,CD4+细胞水平治疗后1个月较治疗前升高.治疗后3个月时较1个月有所下降;CD8+细胞水平治疗后1个月、3个月均高于治疗前;CD4+/CD8+比值治疗后呈下降趋势;B淋巴细胞水平呈上升趋势:NK细胞治疗后较治疗前降低.脾脏微波消融体积20%-40%组CD3、CD4+、CD4+/CD8+比值、B细胞、NK细胞水平治疗后1个月、3个月均高于治疗前水平,呈上升趋势;CD8+细胞水平治疗后1个月、3个月低于治疗前水平,并一直呈下降趋势.其中治疗后3个月,该组CD4+T淋巴细胞水平明显高于消融体积≤20%组.结论 微波定量消融脾脏治疗脾大、脾亢的疗法是一种微创的相当于部分手术切除脾脏的治疗方法,不仅维持了脾脏免疫功能还可提高机体免疫水平;微波消融脾脏体积大小与治疗后机体免疫功能的恢复和维持有关.     

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.     

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.