肺血栓栓塞症患者一氧化氮和血小板功能的变化

目的研究肺血栓栓塞症患者溶栓抗凝治疗前后一氧化氮(NO)和血小板功能的变化。方法流式细胞仪检测肺血栓栓塞患者和健康者血小板P-选择素(Ps)的表达,同时测定血浆中NO、血管性血友病因子(vWF)、血栓素B2(TXB2)和6酮--前列腺素F1α(6-keto-PGF1α),比较治疗前后一周各项指标的变化。应用NO的前体L精-氨酸(L-Arg)处理后,检测其血小板上Ps表达及N-硝基-L精氨甲基酯(L-NANE)预处理后L-Arg对血小板上Ps的表达的影响。结果PTE组Ps、vWF、TXB2的水平显著高于对照组,而治疗后明显下降(P均<0.01);NO和6-keto-PGF1α显著低于对照组,治疗后明显升高(P均<0.01)。应用L-Arg后,血小板Ps表达减少,L-NAME预处理可明显阻断这一效应。结论PTE患者存在明显的血管内皮损伤,NO的水平降低,这可能是PTE患者血小板Ps表达增加,促进血小板活化,导致PTE进一步发展的原因之一。     

犬急性肺血栓栓塞部分血管活性物质的实验研究

目的　探讨内皮素(ET)、一氧化氮(NO)、肾上腺髓质素(ADM)和C型利钠肽(CNP)在肺血栓栓塞时的变化及对血流动力学的影响。方法　14只健康杂种犬随机分为肺栓塞组和对照组。栓塞组注射自体血栓,对照组注射温生理盐水。每只犬在注栓前、注栓后的半小时、1、2、4及6h各时点记录血流动力学指标和进行动脉血气分析,收集动脉血标本,检测ET、CNP、ADM和NO的变化。结果　组织病理符合肺血栓栓塞的改变;栓塞组在栓塞后动脉血气血氧分压较栓塞前及对照组明显降低(P <0 .0 5 ) ;栓塞组在栓塞后平均肺动脉压(MPAP)和肺血管阻力(PVR)较栓塞前及对照组明显升高(P<0 .0 5 ) ;与对照组比较,ET和NO在栓塞后2、4及6h明显升高(P <0 .0 5 )。ADM在栓塞后1、2h明显升高(P <0 .0 5 ) ;CNP在栓塞后2h明显升高(P <0 .0 5 )。结论　血管活性物质ET、NO、ADM和CNP参与急性肺血栓栓塞的病理生理过程。     

实验性肺栓塞溶栓血管紧张素I和血管紧张素Ⅱ变化的意义

目的 探讨兔实验性肺栓塞症（PTE）溶栓前后血管紧张素Ⅰ（ANGⅠ）和血管紧张素Ⅱ（ANGⅡ）变化及其临床意义。方法 健康中国大耳白兔30只,按照随机数字法将实验动物分为肺栓塞组,对照组和溶栓组,每组10只。栓塞组和溶栓组自颈静脉注入自体小血凝块建立家兔急性肺栓塞模型,溶栓组从耳静脉注入尿激酶。结果 栓塞组兔的肺表面凸凹不平,有散在苍白病灶,并可见点片状出血灶,镜下肺动脉血管内可见有注入的血凝块,血管壁炎症细胞浸润及间质出血。栓塞后5d处死的家兔可见栓塞灶内有肉芽组织形成。肺栓塞后ANGⅠ 1h开始持续升高,2h达高峰;溶栓组2h后变化无显著差异;栓塞组ANGⅡ 1h明显升高并持续,与栓塞前相比均有显著差异。溶栓组1h开始升高2h达高峰,此后开始下降至与栓塞前相比无显著差异。结论 PTE兔4h内ANGⅠ和ANGⅡ有不同程度的升高,溶栓后明显降低,故PTE的溶栓或一般治疗中用拮抗剂（ACEI）或受体拮抗剂（ARB）是有益的。     

纤溶系统失衡与肺血栓栓塞症的关系

本文对纤溶系统的主要组成成分组织型纤溶酶原激活剂(t-PA)、尿激酶(u-PA)和Ⅰ型纤溶酶原激活物抑制剂(PAI-1)的动态变化在肺血栓栓塞症(PTE)发生发展中的作用进行综述,表明纤溶系统失衡在PTE早期血栓形成中起重要作用。     

溶栓和抗凝治疗对肺血栓栓塞患者血管内皮细胞及凝血纤溶功能的影响

目的探讨肺血栓栓塞症(PTE)患者溶栓、抗凝治疗前后不同时相血管内皮细胞和凝血纤溶功能的变化及其临床意义。方法用重组组织型纤溶酶原激活物(rt-PA)溶栓治疗PTE患者7例(溶栓组),用低分子肝素(LMWH)为主的抗凝药物治疗PTE患者17例(抗凝组),动态观察两组患者溶栓、抗凝前后不同时相(溶栓组于溶栓治疗前及治疗结束后4、24h,4、7d5个时相;抗凝组于抗凝治疗前及治疗开始后24h,7、14d4个时相)内皮素-1(ET-1)、一氧化氮(NO)、组织型纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制物1(PAI-1)、抗凝血酶Ⅲ(AT-Ⅲ)、D-二聚体(D-dimer)等指标的变化,并将两组患者治疗前上述指标的检测结果与20名正常人(对照组)的结果进行比较。结果溶栓组溶栓后4h ET-1、D-dimer均有一明显的高峰出现,分别为(103.7±26.6)ng/L、(5.0±1.7)mg/L,与其他时相比差异均有统计学意义(前者P<0.05、后者P<0.01)。抗凝组抗凝后14d与抗凝前比较,ET-1由(72.0±18.3)ng/L降至(52.8±13.9)ng/L,NO由(48±14)μmol/L升至(66±24)μmol/L,AT-Ⅲ由(90±7)%升至(99±4)%(P均<0.05)。溶栓后4h ET-1的升高与PaO2、D-dimer的升高程度正相关(r值分别为0.751、0.782,P均<0.05)。结论ET-1、D-dimer的水平在溶栓前后,ET-1、NO、AT-Ⅲ的水平在抗凝前后均发生了变化,溶栓后早期ET-1、D-dimer的变化可反映溶栓效果。溶栓和抗凝治疗有助于调节凝血纤溶平衡和保护血管内皮细胞功能。     

急性肺栓塞大鼠血管内皮功能动态观察

目的探讨急性肺栓塞大鼠血浆内皮素(ET)、NO水平的动态变化,了解血管内皮功能的改变。方法雄性SD大鼠32只,随机分为对照组、栓塞24h组、栓塞1周组、栓塞2周组,每组8只。医用明胶海绵微粒制备大鼠急性肺栓塞模型,测定血浆ET、NO,HE染色。结果与对照组比较,栓塞24h组、栓塞1周组、栓塞2周组大鼠血浆ET水平呈持续升高状态,NO水平呈持续降低状态。光镜下观查,栓塞2周组大鼠肺动脉内明胶海绵多数溶解。结论急性肺栓塞大鼠血浆ET和NO水平与肺血管内皮功能损伤有关。     

基质金属蛋白酶9及金属蛋白酶组织抑制剂1在肺血栓栓塞相关肺血管重构中的作用探讨

目的 通过颈外静脉注入自体血凝块并应用氨甲环酸建立大鼠肺血栓栓塞症(PTE)相关肺血管重构动物模型,探讨基质金属蛋白酶9(MMP-9)及金属蛋白酶组织抑制剂1(TIMP-1)在PTE相关肺血管重构中的作用.方法 将56只SD大鼠随机分为PTE组及假手术组(Sham组).PTE组用注入血栓及抑制纤溶方法 制作PTE模型.Sham组用生理盐水代替血栓及抗纤溶药物.每组分别于制模后1、3、7、14 d各取7只鼠处死,留血检测 MMP-9、TIMP-1 含量.取左肺做苏木素伊红染色、磷钨酸苏木素(PTAH)染色及α- 平滑肌肌动蛋白(α-SMA)免疫组织化学(IH)染色,并做 MMP-9、TIMP-1 IH 及原位杂交(ISH)染色.结果 ①PTE组制模第7天见到栓塞部位肺血管重构,14 d 时更加明显.②PTE组血清 MMP-9 浓度及 MMP-9/TIMP-1 比值均高Sham(P0.01),TIMP-1在1 d 及3 d 时显著高于Sham组(P＜0.05,P＜0.01),7 d与14 d 时降至 Sham 组水平.③PTE 组 IH 染色显示栓塞部位的血管及新生内膜中的平滑肌细胞内皮细胞及浸润的单核一巨噬细胞,MMP-9 染色阳性.栓塞部位的血管内皮细胞及平滑肌细胞 TIMP-1染色阳性.Sham 组 MMP-9及 TIMP-1 染色阴性或弱阳性.MMP-9 及 TIMP-1 ISH染色结果与 IH 染色结果 基本一致.④α-SMA染色显示平滑肌细胞是新生内膜的主要成分.结论 颈外静脉注入自体血栓并重复应用抗纤溶药物可成功建立大鼠PTE相关肺血管重构模型,PTE相关肺血管重构的主要病理改变为新生内膜生成.MMP-9/TIMP-1失调参与了PTE相关肺血管重构过程.     

溶栓治疗对老年肺血栓栓塞患者凝血纤溶功能的影响

目的探讨溶栓治疗老年肺血栓栓塞症(PTE)的疗效及对患者凝血纤溶功能的影响。方法回顾性分析2010年4月至2013年3月河北省唐山市工人医院收治的60例老年PTE患者的临床资料,根据治疗方法的不同分为观察组和对照组,每组30例。观察组采用尿激酶溶栓治疗,对照组使用低分子肝素(LMWH)为主的抗凝治疗。对比观察两组治疗前后凝血纤溶功能相关指标纤维蛋白原(Fib)、D-二聚体(D-D)和抗凝血酶Ⅲ活性(AT-Ⅲ)的变化、疗效和不良反应发生率。结果治疗后观察组Fib、D-D较治疗前显著降低,AT-Ⅲ显著升高,对照组AT-Ⅲ较治疗前显著升高(均P<0.05),Fib、D-D无明显变化(P>0.05),且治疗后观察组AT-Ⅲ显著高于对照组(P<0.05);观察组有效率为93.3%,显著高于对照组的60.0%(P<0.05);两组患者不良反应比较差异不明显(P>0.05)。结论溶栓治疗老年PTE疗效显著,可有效改善患者凝血纤溶功能,其安全性还需要进一步深入研究。     

组织型纤溶酶原激活剂及其抑制剂与肺血栓栓塞症

肺血栓栓塞症（PTE）的发病与机体的纤溶和凝血系统功能密切相关。组织型纤溶酶原激活物（t-PA）及其抑制物（PAI-1）因调节机体的纤溶系统而在静脉血栓形成及栓塞性疾病的发病机制中发挥重要作用,因此,本文对t—PA和PAI-1与PTE的关系作如下综述。     

老年代谢综合征患者血管内皮功能与血栓前状态的研究

目的　观察老年代谢综合征 (MS)患者的血管内皮功能 ,及其与血栓前状态的关系 ,以了解心血管危险因素对血管内皮功能和血栓前状态的影响。方法　利用高分辨率超声显像方法检测MS患者肱动脉血管内皮依赖性舒张功能 (FMD)和非内皮依赖性舒张功能 (NMD) ,同时检测了部分反映血管内皮功能的血管活性物质和反映凝血纤溶活性的分子标记物。结果　老年MS组FMD低于对照组 (P <0 0 1 ) ;MS组与对照组相比 ,NMD亦有降低 ,有显著性差异 (P <0 0 5) ,MS组ET升高 (P <0 0 5) ,PAI 1升高 (P <0 0 1 ) ,DD较对照组升高 ,差异显著 ;NO降低 (P <0 0 1 ) ;t PA降低 (P <0 0 5)。多元回归分析显示老年MS患者FMD与年龄 ,BMI,SBP ,DBP ,FBG ,TC ,TG呈负相关。结论　老年MS患者血管内皮依赖性舒张功能受损 ,与年龄 ,血压 ,血糖 ,血脂水平 ,体重指数相关 ;同时存在血栓前状态 ;与内皮功能失调密切相关 ;MS治疗应全面控制心血管危险因素 ,逆转血管内皮功能 ,同时应用抗血小板药物     

犬肺血栓栓塞症模型的改进

目的 :为解决监测犬D 二聚体的试剂盒获取不易、价格昂贵的问题 ,改进犬急性肺血栓栓塞症 (PTE)的模型 ,探讨该模型在急性PTE研究中的价值。方法 :采用犬自体血加凝血酶加人纤维蛋白原制备的自体血栓 ,由股静脉输入建立急性PTE的模型 ,并分别与不同的 2组对照组比较。监测肺血流动力学的变化 ,作肺动脉造影、螺旋CT及螺旋CT血管造影 ,栓塞前及栓塞后多时点留取血样测血浆D 二聚体浓度。栓塞后 1d ,5d ,10d分别处死部分犬做病理解剖学观察。结果 :实验组及对照Ⅰ组均存在肺动脉栓塞。栓塞后即刻肺动脉收缩压 (PASP)、肺动脉舒张压 (PADP)明显上升 ,自身前后及与对照Ⅱ组比较有显著性差异 (P <0 0 5 )。实验组血浆D 二聚体于栓塞后 30min明显上升 ,1～ 2h达高峰 ,2 4h后下降 ,自身前后及与对照Ⅰ组、对照Ⅱ组比较 ,有显著性差异 (P <0 0 5 )。结论 :犬急性PTE模型改进成功。血浆D 二聚体在急性PTE早期有一个相对特征性的动态变化过程 ,动态检测血浆D 二聚体有助于急性PTE的早期诊断。     

肺血栓栓塞症患者凝血纤溶系统及肺血管内皮功能的变化

目的探讨肺血栓栓塞症(PTE)患者体内凝血纤溶系统及肺血管内皮功能的变化及其临床意义。方法采用酶联免疫吸附测定(ELISA)检测80例PTE患者(急性大面积PTE组20例、非大面积PTE组60例)、40名正常人(对照组)的血D-二聚体(D-D)、组织型纤溶酶原激活剂(t-PA)、纤溶酶原激活剂抑制物1(PAI-1)、血浆蛋白S(Ps)、血浆蛋白C(Pc)、凝血酶调节蛋白(TM)、抗心磷脂抗体(ACA)、同型半胱氨酸(Hcy)含量;采用发色底物法检测抗凝血酶Ⅲ活性(AT-Ⅲ)。结果急性大面积PTE组患者血D-D、t-PA、PAI-1、Ps、TM、含量分别为(1.46±0.62)mg/L、(11.4±6.9)μg/L、(88.2±27.5)μg/L、(22.40±9.40)mg/L、(6.8±1.1)μg/L,非大面积PTE组分别是(0.92±0.27)mg/L、(6.6±1.5)μg/L、(60.1±26.1)μg/L、(23.90±10.70)mg/L、(6.3±1.5)μg/L,均显著高于正常对照组的(0.38±0.10)mg/L、(4.7±1.4)μg/L、(35.7±9.2)μg/L、(16.10±6.20)mg/L、(3.0±0.5)μg/L(分别P<0.01、<0.05)。急性大面积PTE组患者血AT-Ⅲ含量为(86.0±11.8)%,非大面积PTE组为(90.1±9.0)%,显著低于正常对照组的(102.6±9.20)%(P分别<0.01、0.05)。两PET组患者ACA-IgG、IgM、IgA显著高于正常对照组,差异有统计学意义(P<0.05)。结论PTE患者存在凝血纤溶系统功能失衡和肺血管内皮损伤。     

溶栓剂和内皮素受体拮抗剂对犬急性肺血栓栓塞症肺动脉压的影响

目的：探讨溶栓剂和（或）内皮素受体拮抗剂对于实验犬急性肺血栓栓塞症（PTE）肺动脉压（PAP）的影响。方法：20只草犬随机分为假手术组、模型对照组、溶栓剂尿激酶组（UK组）、内皮素受体拮抗剂组（BQ123组）和尿激酶联合BQ123组（联合组）共5组，分别给予假手术操作、注入自体血栓、注入自体血栓加UK、注入自体血栓加BQ123以及注入自体血栓加UK和BQ123。结果：接受UK和（或）BQ123组PAP升幅（APAP）明显降低。在造模后2．5h，模型组PAP升高（7．70±1．72）mmHg（1mm Hg=0．133kPa），而UK组仅升高（5．56±1．26）mm Hg，BQ123组升高（3．83±1．60）mm Hg，联合组则下降（1．70±0．72）mmHg，P〈0．001；与联合组相比，UK组、BQ123组PAP水平均有显著性差异。结论：尿激酶和BQ123均能显著降低PAP，两者合用效果更明显，提示溶栓剂和内皮素受体拮抗剂联合治疗在急性FTE的治疗中具有重要意义。     

In patients with deep-vein thrombosis elevated levels of factor VIII correlate only with von Willebrand factor but not other endothelial cell-derived coagulation and fibrinolysis proteins.

Several studies have shown that patients with venous thrombosis have elevated levels of factor VIII (FVIII) at an increased frequency. Most such patients also have high von Willebrand factor (vWF) levels. Since vWF is synthesized by the vascular endothelium, we hypothesized that elevated FVIII levels would also be associated with an increase of other endothelial cell-derived coagulation proteins suggesting perturbation of the endothelium. In 100 healthy individuals and 129 patients with venous thromboembolism, we have determined antigenic FVIII levels along with several endothelial proteins including vWF, soluble thrombomodulin (sTM), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1). Levels of FVIII, vWF, PAI-1 and t-PA were significantly increased in patients compared with the controls (FVIII, vWF, and PAI-1,P < 0.001; t-PA, P < 0.05). Levels of sTM, however, were higher in the controls than in the patients (P < 0.001). Whereas the FVIII levels correlated well with the vWF levels in the patients (correlation, 0.61; P < 0.001) and the controls (correlation, 0.70; P < 0.001), there was neither a relevant correlation between FVIII and sTM, PAI-1, and t-PA, nor between vWF and sTM, PAI-1, and t-PA in the patients and the controls. In conclusion, although levels of PAI-1 and t-PA can be found, on average, at increased levels in patients with thrombosis, FVIII levels correlate only with vWF but not other endothelial cell-derived coagulation and fibrinolysis proteins including sTM, PAI-1, and t-PA.     

瑞舒伐他汀对血脂正常阻塞性睡眠呼吸暂停综合征合并高血压患者血栓前状态的影响

目的 研究瑞舒伐他汀对血脂正常的阻塞性睡眠呼吸暂停综合征（OSAS）合并高血压患者血栓前状态的影响.方法 血脂正常的OSAS合并高血压患者75例,随机分成瑞舒伐他汀组40例,常规治疗组35例,另选取25名门诊健康体检者作为对照组.检测一氧化氮（NO）、内皮素（ET-1）及血管性假性血友病因子（vWF）、血小板颗粒膜蛋白（GMP-140）、组织型纤溶酶原激活剂（t-PA）、纤溶酶原激活物抑制剂-1（PAI-1）的水平变化.结果 ①治疗前两组OSAS合并高血压患者NO、t-PA低于健康对照组,差异有统计学意义（P＜0.05）;ET-1、vWF、GMP-140、PAI-1水平均高于健康对照组,差异有统计学意义（P＜0.01）.②治疗后瑞舒伐他汀组及常规治疗组NO、t-PA水平均较治疗前升高,瑞舒伐他汀组NO、t-PA高于常规治疗组,差异有统计学意义（P＜0.05）.③治疗后瑞舒伐他汀组及常规治疗组ET-1及vWF、GMP-140、PAI-1均较治疗前降低,瑞舒伐他汀组ET-1、vWF,GMP-140低于常规治疗组,差异有统计学意义（P＜0.01）.结论 对于血脂正常的OSAS合并高血压患者,瑞舒伐他汀可通过提高血浆NO、t-PA浓度和降低ET-1、vWF、GMP-140、PAI-1浓度等非调脂机制改善血栓前状态.     

二氧化碳气腹时间对老年腹腔镜胆囊切除术患者凝血-纤溶和血管内皮细胞活性的影响

目的 观察二氧化碳(CO2)气腹时间对老年人腹腔镜胆囊切除术(LC)患者凝血-纤溶和血管内皮细胞活性的影响.方法 胆石症择期行LC患者45例,年龄＞60岁,术后根据气腹持续时间分组:气腹时间≤60 min组21例;气腹时间＞60 min组24例.于入院检查时(术前)、术毕、术后第1、2、3天抽取静脉血检测凝血酶原时间(PT)、激活部分凝血活酶时间(APTT)、凝血酶原片段1+2(F1+2)浓度、抗凝血酶-Ⅲ(AT-Ⅲ)活性、纤维蛋白原(Fib)浓度、组织纤溶酶原激活物(t-PA)浓度、纤溶酶原激活物抑制物-1(PAI-1)浓度、D-二聚体(D-D)浓度、血管性血友病因子(vWF)活性.结果 (1)凝血指标:术后第3天,＞60 min组的,F1+2为 (1.60±0.26) μg/L,高于≤60 min组的(1.32±0.24) μg/L(P＜0.05);AT-Ⅲ为(84.82±20.21)%,低于≤60 min组的(97.49±16.87)%(P＜0.05);术后第2、3天的Fib分别为(3.87±0.62)、(3.98±0.77)g/L,高于≤60 min组的 (3.42±0.72)、(3.42±0.63)g/L(P＜0.05).(2)纤溶-抗纤溶指标:＞60 min组术后第2 、3天的PAI-1为(33.93±10.42)、(32.90±11.25) μg/L高于≤60 min组的(26.69±9.49)、(26.31±7.06)μg/L(P＜0.05).(3)血管内皮细胞活性指标:＞60 min组术后第2 、3天的vWF为(174.53±44.03)%、(176.31±47.6)%,高于≤60 min组的(134.37±37.74)%、(131.21±36.34)% (P＜0.05).结论 老年LC患者,术后有明显的凝血-纤溶激活和血管内膜损伤;随气腹时间延长,凝血激活和纤溶抑制程度高,凝血-纤溶相对不平衡,血管内膜损伤更明显,可能增加血栓形成风险.

Abstract：

Objective To observe the effect of duration of carbon dioxide pneumoperitoneum on coagulation, fibrinolysis and endothelial activation in elderly patients undergoing laparoscopic cholecystectomy (LC). Methods The 45 elderly patients with cholelithiasis scheduled for LC, aged over 60 yeas, were placed in different groups respectively after surgery according to the duration of pneumoperitoneum. The duration of pneumoperitoneum was ≤60 minutes in group A (n=21),and more than 60 minutes in group B (n=24). Venous blood samples were taken on admission (baseline), at the end of surgery, the 1st, 2nd and 3rd day after surgery for determination of prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin fragment F1+2 (F1+2), antithrombin 3 (AT-Ⅲ activity), fibrinogen (Fib), tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAI-1), D-dimer (D-D), von Willebrand factor (vWF activity). Results Concerning the coagulation activation, at the 3rd postoperative day, the level of F1+2 was significantly higher in group B than in group A [(1.60±0.26) μg/L vs. (1.32±0.24) μg/L, P＜0.05]; AT-III was significantly higher in group B than in group A [(84.82%±20.21%) vs. (97.49%±16.87%), P＜0.05]. At the 2nd and 3rd postoperative day, the levels of Fib were significantly higher in group B than in group A [(3.87±0.62) g/L vs. (3.42±0.72) g/L, (3.98±0.77) g/L vs. (3.42±0.63) g/L, respectively, P＜0.05]. Concerning fibrinolysis, But at the 2nd and 3rd postoperative day, the level of PAI-1 was significantly higher in group B than in group A [(33.93±10.42) μg/L vs. (26.69±9.49) μg/L, (32.90±11.25) μg/L vs. (26.31±7.06) μg/L respectively, P＜0.05]. Concerning endothelial activation, at the 2nd and 3rd postoperative day, vWF was significantly higher in group B than in group A [(174.53%±44.03%) vs. (134.37%±37.74%), (176.31%±47.6%) vs. (131.21%±36.34%), respectively, P＜0.05]. Conclusions Marked activations of coagulation-fibrinolysis and endothelial activation are observed postoperatively in elderly patients undergoing laparoscopic cholecystectomy. Along with prolonged duration of pneumoperitoneum, more pronounced alterations of increased coagulation, reduced fibrinolysis and endothelial activation are observed, which could constitute an imbalanced situation of coagulation-fibrinolysis and increases the risk of venous thrombosis.     

Altered endothelial function in lambs with pulmonary hypertension and acute lung injury

Acute lung injury produces pulmonary hypertension, altered vascular reactivity, and endothelial injury. To determine whether acute lung injury impairs the endothelium-dependent regulation of pulmonary vascular tone, 16 lambs were studied during U46619-induced pulmonary hypertension without acute lung injury, or air embolization-induced pulmonary hypertension with acute lung injury. The hemodynamic responses to endothelium-dependent (acetylcholine, ATP, ET-1, and 4 Ala ET-1 [an ETb receptor agonist]) and endothelium-independent (nitroprusside and isoproterenol) vasodilators were compared. During U46619-induced pulmonary hypertension, all vasodilators decreased pulmonary arterial pressure and vascular resistance (P < 0.05). During air embolization-induced pulmonary hypertension, the pulmonary vasodilating effects of acetylcholine, ATP, and 4 Ala ET-1 were attenuated (P < 0.05); the pulmonary vasodilating effects of nitroprusside and isoproterenol were unchanged; and the pulmonary vasodilating effects of ET-1 were reversed, producing pulmonary vasoconstriction (P < 0.05). During air embolization, the pulmonary vasoconstricting effects of ET-1 were blocked by BQ 123, an ETa receptor antagonist. The systemic effects of the vasoactive drugs were similar during both conditions. We conclude that pulmonary hypertension with acute lung injury induced by air embolization results in endothelial dysfunction; there is selective impairment of endothelium-dependent pulmonary vasodilation and an altered response to ET-1 from pulmonary vasodilation to vasoconstriction. This altered response to ET-1 is associated with decreased ETb receptor-mediated vasodilation and increased ETa receptor-mediated vasoconstriction. Endothelial injury and dysfunction account, in part, for the altered regulation of pulmonary vascular tone during pulmonary hypertension with acute lung injury.     

Regional left atrial coagulation and fibrinolytic activities in patients with mitral stenosis

Systemic thromboembolism is a major complication of mitral stenosis (MS), especially in those patients having atrial fibrillation (AF). Recent evidence has suggested that regional left atrial coagulation activity may be increased in MS and may contribute to the pathophysiology of left atrial thrombus. However, the relation of left atrial coagulation activity to factors that predispose to left atrial thrombus formation is unknown. Also, the relations between left atrial and systemic coagulation activity, fibrinolysis, and platelet activation remain unresolved. Left atrial and peripheral venous levels of fibrinogen, antithrombin III, factor VII and factor VIII for coagulation, D-dimer, tPA and PAI-I, plasmin and antiplasmin for fibrinolysis, and platelet factor 4 and vWF for platelet activation, and endothelial dysfunction were measured in 46 patients with MS and normal clotting times who were undergoing percutaneous mitral valvuloplasty. Left atrial tPA, plasmin, PAI-I, antiplasmin, PF4, and vWF levels exceeded the corresponding peripheral venous levels (P < 0.05) in patients with MS, being more significant in the AF subgroup. There were no significant differences between left atrial and peripheral venous levels of fibrinogen, D-dimer, factor VII, and factor VIII within the patient group (P > 0.05). The results suggest that there are significant variations in the indices of coagulation, fibrinolytic system and platelet activation, and endothelial dysfunction between left atrial and peripheral venous blood samples of patients with MS that may be due to limited spillover from the left atrium to the systemic circulation.