门静脉高压犬肝缺血再灌注时肺循环血液动力学及NO/ET和PGI2/TXA2的变化

目的 评价门静脉高压犬肝缺血再灌注时肺循环血液动力学及肺循环一氧化氮(NO)/内皮素(ET)和前列腺素I2(PGI2)/血栓素A2(TXA2)的变化.方法 健康家犬12只,雌雄不拘,体重10～18 kg,随机分为2组(n=6):对照组和模型组.模型组采用部分结扎门静脉的方法 建立犬门静脉高压模型,12周后完全阻断门静脉、肝后下腔静脉30 min,再灌注60 min制备肝缺血再灌注模型.于第2次麻醉后即刻、肝缺血前即刻、缺血5、30 min、再灌注前即刻、再灌注5、10、15、30和60 min(T1-10)时记录心率(HR)、心输出量(CO)、中心静脉压(CVP)、肺动脉楔压(PAWP)和平均肺动脉压(MPAP),计算心脏指数(CI)、肺血管阻力(PVR)和肺血管阻力指数(PVRI),并计算T2-10时CI、CVP、MPAP、PAWP和PVRI相对于T1的变化幅度;于T2、T4和T9时测定肺动脉血浆NO、ET、TXA2和PGI2的浓度,并计算NO/ET和PCI2/TXA2比值.结果 两组肝缺血时CI、CVP、PVRI、PAWP和MPAP均降低,且模型组CI、CVP、PAWP、MPAP降低幅度低于对照组,两组再灌注时CVP、PAWP、MPAP和PVRI均升高,且模型组PAWP和PVRI升高幅度高于对照组(P<0.05或0.01);模型组肝缺血再灌注时肺动脉血浆NO浓度、NO/ET比值和肝缺血时肺动脉血浆TXA2浓度、PGI2/TXA2比值均低于对照组(P<0.01).模型组PVR与肺动脉血浆NO浓度呈负相关(r=-0.567,P<0.05).结论 门静脉高压犬肝缺血再灌注时肺动脉压升高,可能与肺循环NO水平降低、NO与ET失衡有关.     

先天性心脏病合并肺动脉高压患者肺组织一氧化氮合酶的表达

目的：通过观察先天性心脏病合并肺动脉高压患者肺组织内皮型一氧化屡合酶（eNOS)的表达，了解其肺血管内皮细胞功能有否异常。方法：32例先天性心脏病患者分为2组，组I：合并肺动脉高压患者（n=16);组Ⅱ：未合并肺动脉高压患者（n=16)。在心内直视术下，取少许右肺中叶组织，利用免疫组织化学和逆转录－聚合酶链反应（RT－PCR）技术，对eNOS进行半定量分析。结果：组Ⅱ患者肺血管内皮细胞内eNOS免疫染色比组I明显增强（F＝93．98，P＜0．01）；组Ⅱ患者肺血管内皮细胞内eNOSmRNA表达比组I明显增高（F＝58．76，P＜0．01）。结论：先天性心脏病合并肺动脉高压患者的eNOS表达减少，造成内源性一氧化氮（NO）生成不足，为该类患者吸入NO治疗肺动脉高压提供了理论依据。     

室间隔缺损伴肺动脉高压患者血浆内皮素、一氧化氮与肺细小动脉形态变化的关系

目的　探讨内皮素 ( ET- 1)、一氧化氮 ( NO)在肺动脉高压 ( PH)发生、发展过程中的作用。　方法　 60例室间隔缺损患者分为两组 ,无 PH组 :2 0例 ,不合并 PH,平均肺动脉压 ( MPAP) <2 0 mm Hg( 1k Pa=7.5 mm Hg) ;PH组 :4 0例 ,合并 PH,MPAP>2 0 mm Hg。测定两组血浆 ET- 1和 NO含量 ,作肺组织活检 ,观察肺血管的病理改变及测定肺细小动脉显微形态指标。　结果　全部肺标本按阮英茆的 级分类进行病理分级 :无 PH组患者肺血管无明显病理改变 ,PH组患者 级 7例、 级 13例、 级 2 0例 ,未见 级病理改变。随着肺血管病理改变分级的增加 ,血浆ET- 1、NO、血流动力学指标及肺细小动脉显微形态指标测定均呈阶梯样变化 ,除 NO、血管腔面积 /血管总面积 ( EA/ TA)逐渐减小 ,其它指标均逐渐增高 ,ET- 1、NO、MPAP、肺血管阻力 ( PVR)、肺细小动脉中膜厚度 ( m MTPA)、血管壁面积 /血管总面积 ( WA/TA)、EA/ TA和肌型肺细小动脉 /微动脉总数的比值 ( TWPV) ,无 PH组与 PH组 级、PH组 级与 级、 级与 级之间差别均有显著性意义 ( P<0 .0 5 ,0 .0 1) ;血浆 ET- 1与 MPAP、PVR、m MTPA、WA/ TA和 TWPV均呈显著正相关 ,血浆 NO均呈显著负相关 ;血浆 ET- 1与 EA/ TA呈显著负相关 ,血浆 NO呈显著正相关 ( P<0 .0     

吸入伊洛前列素和一氧化氮治疗先天性心脏病术后肺动脉高压

目的 探讨吸入伊洛前列素对先天性心脏病(CHD)术后早期机械通气和持续吸入一氧化氮(NO)的基础上,仍合并肺动脉高压(PH)病儿的疗效及对预后的影响,并初步探讨其作用机制.方法 30例CHD根治手术后在机械通气和持续一氧化氮(NO)吸入的基础上仍合并PAH的病儿,随机分为试验(T)组和对照(C)组.在原治疗基础上,T组给予伊洛前列素100 ng·kg-1·min-1,吸入10 min,C组给予0.9%NaCl 4ml吸入.每4h一次,连续治疗48 h.超声和心电监测观察病儿的血流动力学和呼吸机条件的改变.对比首次吸药前后血浆环磷酸腺苷(cAMP)和环磷酸鸟苷(cGMP)浓度变化.结果 T组停止吸入伊洛前列素后20min,肺动脉收缩压(sPAP)和肺动脉收缩压/主动脉收缩压(sPAP/sBP)明显下降,分别为:(43.23±11.72)mm Hg(1 mm Hg=0.133 kPa)和0.48±0.13,均小于C组(53.13±13.60)mm Hg和0.60 ±0.15,P<0.05.停止吸药120 min,T组sPAP/sBP仍然小于C组(0.48±0.09对0.59±0.14,P<0.05).连续治疗24 h和48 h,T组sPAP和sPAP/sBP继续下降,均明显小于C组(P<0.01).停止首次吸药后20 min,T组cAMP(578.68±193.05)pg/dl较治疗前(406.64±179.18)pg/dl明显升高(P<0.01),也明显大于C组(392.26±94.46)pg/dl(P<0.01).C组2例因肺高压危象(PHC)死亡,T组无死亡.结论 CHD双心室矫正术后早期机械通气和持续吸入NO仍合并PH病儿,吸入伊洛前列素后可明显降低sPAP和sPAP/sBP.伊洛前列素可能减少肺高压危象(PHC)导致的死亡.其扩血管作用可能与血浆cAMP浓度升高有关.     

门、腔静脉阻断与开放对门静脉高压模型犬肺组织与肺动脉iNOS、eNOS和ET表达的影响

目的观察门静脉和下腔静脉阻断与开放后门静脉高压模型犬肺组织和肺动脉的病理学特点及诱生型一氧化氮合酶（iNOS）、内皮型一氧化氮合酶（eNOS）和内皮素（ET）基因与蛋白表达的变化。方法正常家犬18只,随机均分为阴性对照组、对照组和门静脉高压模型组,进行门静脉和肝后下腔静脉阻断与开放实验。在术毕观察右下肺动脉和肺组织病理形态学特征,并检测肺组织和肺动脉iNOS、eNOS和ET基因与蛋白表达的变化。结果模型组与对照组肺组织和肺动脉在经历门、腔静脉阻断与开放后均存在不同程度病理形态学改变,但以模型组改变更为显著;模型组肺组织iNOS和肺动脉iNOS、eNOS基因和蛋白的表达显著强于阴性对照组和对照组（P〈0．05）。结论肺组织和肺动脉在经历门、腔静脉阻断与开放后均存在明显的病理形态学改变。肺动脉iNOS和eNOS基因和蛋白表达水平明显上调,可能在一定程度上参与门静脉高压肝移植围术期肺循环的变化;而门静脉高压肝移植围术期易并发急性肺损伤则可能与肺组织中iNOS基因和蛋白表达水平上调有关。     

体外循环对先天性心脏病合并肺动脉高压患者血浆NO和ADMA浓度的影响

目的 通过观察体外循环(CPB)对先天性心脏病合并肺动脉高压患者血浆一氧化氮(NO)和不对称二甲基精氨酸(ADMA)浓度的影响,分析CPB加重肺动脉高压的原因.方法 拟在CPB下行心内修补术的先天性心脏病患者18例,年龄11～40岁,体重26～59 kg,ASAⅡ或Ⅲ级,心功能Ⅰ～Ⅲ级.根据术前肺动脉收缩压(PASP)分为3组(n=6),Ⅰ组肺动脉压正常(PASP<30 mm Hg);Ⅱ组肺动脉压轻度增高(PASP 30～50 mm Hg);Ⅲ组肺动脉压中重度增高(PASP>50 mm Hg).分别于麻醉诱导前(基础状态)、CPB开始即刻、CPB停机后即刻、3、6和24 h时采集桡动脉血样4 ml,测定血浆NO和ADMA浓度.结果 与基础值相比,Ⅱ组和Ⅲ组CPB停机后即刻、3和6 h时血浆ADMA浓度升高,NO浓度降低(P<0.05),Ⅰ组上述指标差异无统计学意义(P>0.05).与Ⅰ组比较,Ⅱ组和Ⅲ组血浆NO浓度降低,ADMA浓度升高(P<0.05).结论 CPB可引起先天性心脏病合并肺动脉高压患者血浆ADMA浓度升高,NO浓度降低.     

重组人内皮型一氧化氮合酶基因转染对增生性瘢痕成纤维细胞的影响

目的 了解重组人内皮型一氧化氮合酶(eNOS)基因转染人增生性瘢痕成纤维细胞(HSFb)的可行性,以及转染后一氧化氮(NO)的生成和Ⅰ、Ⅲ型胶原的合成情况. 方法体外构建人eNOS真核表达载体.取体外培养的人HSFb进行转染实验,根据细胞培养液中所加质粒不同分为pcDNA3.0空载体组、pcDNA3.0-eNOS转染组.另设未转染组,细胞按常规培养.采用实时荧光定量PCR法检测各组细胞eNOS及Ⅰ、Ⅲ型胶原mRNA表达.硝酸还原酶法测定NO含量. 结果细胞转染后eNOS显著表达,pcDNA3.0-eNOS转染组eNOS mRNA相对表达量为5.92±0.21,明显高于pcDNA3.0空载体组(0.98±0.13,P<0.05);pcDNA3.0-eNOS转染组Ⅰ型胶原mRNA相对表达量为0.76±0.15,Ⅲ型胶原mRNA相对表达量为0.79±0.08,均明显低于pcDNA3.0空载体组(0.98±0.15、1.02±0.12,P<0.05).pcDNA3.0-eNOS转染组NO含量为(36.1±0.8)μmol/L,明显高于pcDNA3.0空载体组(28.4±1.0)μmol/L和未转染组[(27.7±1.3)μmol/L,P<0.01]. 结论 HSFb可作为eNOS基因转染的靶细胞,转染的细胞能表达eNOS并产生NO,并且对细胞的胶原合成功能有抑制作用.     

前列环素在门静脉高压症内脏高动力循环中的作用及机制

目的:研究前列环素(PGI2)在门静脉高压症(PHT)内脏高动力循环形成中的作用及机制。方法:观察四氯化碳致肝硬化门静脉高压症组(PHT组,n=8)和对照组(N组,n=8)大鼠的门静脉压力(PP)、离体肠系膜微动脉对去甲肾上腺素(NE)的反应性、肠系膜动脉内环氧合酶(COX)表达和下腔静脉血浆6-酮-前列腺素F1α(6-keto-PGF1α)浓度,以及吲哚美辛(INDO)对PHT组大鼠的影响。结果:①PHT组PP和6-keto-PGF1α浓度明显高于N组[(14.50±0.87)mm Hg比(7.63±0.48)mm Hg,(78.73±4.57)ng/L比(51.60±5.23)ng/L,P0.05],INDO能使PHT组6-keto-PGF1α浓度明显下降[(76.57±5.58)ng/L比(42.00±8.75)ng/L,P<0.01];②PHT组肠系膜微动脉对NE的反应性明显低于N组,EC50明显增大,INDO能部分改善这种低反应性;③PHT组肠系膜动脉内COX-1表达较N组明显上调,但COX-2在PHT组和N组均未检测到。结论:肝硬化PHT中过度生成的PGI2可通过降低肠系膜动脉对NE的反应性参与高动力循环的形成,并且PGI2合成增多与血管内过度表达的COX-1有关,与COX-2无关。     

电针刺足三里穴对脓毒症大鼠心脏损害机制的研究

目的 探讨电针足三里穴对脓毒症大鼠心脏功能和结构的影响及机制.方法 将24只SD成年大鼠随机分为假手术组+电针非经非穴组(N +SEA),假手术+电针足三里组(N+EA),脓毒症+电针足三里组(CLP+ EA),脓毒症+电针非经非穴组(CLP+ SEA),共4组(n=6).采用盲肠结扎穿孔术(CLP)法制备大鼠脓毒症模型.N+EA组和CLP+ EA组电针足三里穴,N+SEA组和CLP+ SEA组电针非经非穴.6h后,摘除心脏固定于Langendofff灌流装置;置入左心导管,测定大鼠心脏左室舒张末压(LVEDP)、左心室收缩末期压力(LVSP),左室压最大上升速率(dp/dtmax)、心脏输出量(CO)和心率(HR).最后取心脏组织行免疫组织化学和实时定量聚合酶链反应(Real-time PCR)检测基质金属蛋白酶(MMP)-2、MMP-9及金属蛋白酶组织抑制因子(TIMP)-1、TIMP-2的表达.结果 CLP+ SEA组LVEDP[(5.2±0.9) mm Hg(1 mmHg=0.133 kPa)]、LVSP[(95.2 ±9.3)mm Hg],dp/dt max[(1804±122) mm Hg/s]、CO[(26.6±4.0)ml/min]和HR[(237±15) bpm],均较N+SEA组LVEDP[(9.9±1.6) mm Hg、LVSP[(127.8 ±8.7)mm Hg],dp/dt max[(2484 ±98) mm Hg/s]、CO[(43.10 ±5.30) ml/min]和HR[(310±12) bpm],N+ EA组LVEDP[(9.6±1.7) mmHg]、LVSP[(128.3±9.9)mm Hg],dp/dt max[(2536±107) mm Hg/s]、CO (45.9±5.7) ml/min和HR(312±15) bpm,明显降低(P＜0.01),而CLP+EA组LVEDP[(7.9±0.9) mm Hg]、LVSP[(112.0±11.9) mm Hg],dp/dt max[(2270±152) mm Hg/s]、CO[(35.6±5.1) ml/min]和HR[(280±24) bpm],较CLP+ SEA组明显改善(P＜0.01),在免疫组织化学检测中可见CLP+ SEA组MMP-2、MMP-9及TIMP-1、TIMP-2的表达明显增强,而CLP+ EA组MMP-2、MMP-9及T1MP-1、TIMP-2的表达则在一定程度上减弱.在mRNA水平上,CLP+ SEA组MMP-2(1.47±0.06)、MMP-9(1.59 ±0.04)、TIMP-2 (1.21±0.03)、TIMP-1(1.24±0.04)的mRNA表达明显增加(P＜0.01),而CLP+ EA组中MMP-2(1.30±0.09)、MMP-9(1.38±0.05)、TIMP-2(1.35±0.07)、TIMP-1(1.42±0.07)的表达较CLP+ SEA组均有不同程度的下降(P＜0.05).结论 电针刺足三里可减轻脓毒症大鼠心肌受损,改善血流动力学指标,其机制可能是电针刺足三里穴抑制了MMP-2和MMP-9的表达,改善两者与其特异性抑制剂表达的失衡,并同时激活了胆碱能抗炎通路.     

NOSTRIN在无精子症患者睾丸组织中的表达

目的:通过测定无精子症患者睾丸组织中内皮型一氧化氮合酶运输介导物(NOSTRIN)和内皮型一氧化氮合酶(eNOS)的表达,探讨其与无精子症发病的相关性。方法:采用免疫组化法检测17例特发性无精子症患者(病例组)和10例正常男性(正常组)睾丸组织中NOSTRIN的定位和定量表达;RT-PCR检测睾丸组织中NOSTRINmRNA的表达;分光光度法测定睾丸组织中eNOS的活性;应用硝酸还原酶法测定睾丸组织上清液中NO代谢产物亚硝酸基/亚硝基(NO2-/NO3-)水平。结果:NOSTRIN在睾丸组织中表达于生精细胞、支持细胞以及血管内皮细胞,NOSTRIN在特发性无精子症患者睾丸中的表达水平显著低于正常男性;病例组患者睾丸组织中NOSTRINmRNA呈弱表达(0.312±0.076),明显低于正常组(0.793±0.082,P<0.01);病例组患者睾丸组织eNOS活性[(33.727±3.58)U/mg]与正常组[(17.69±3.84)U/mg]比较显著增高(P<0.01);病例组患者睾丸中NO2-/NO3-水平为[(48.56±8.49)μmol/L],与正常组[(25.37±9.61)μmol/L]比较显著升高(P<0.01);病例组睾丸组织中NOSTRIN表达水平与eNOS活性呈负相关(r=-0.57,P<0.01),与NO代谢产物NO2-/NO3-同样呈负相关(r=-0.61,P<0.01)。结论:无精子症患者睾丸组织中NOSTRIN表达水平降低,eNOS活性增强,NO-/NO-水平升高,这可能与无精子症的发生有着相关性。     

Regional expression of inducible nitric oxide synthase in the kidney in dogs with unilateral ureteral obstruction

PURPOSE: In the early stage of unilateral ureteral obstruction total renal blood flow increases but medullary blood flow decreases, exacerbating medullary tissue hypoxia. We examined the expression of inducible nitric oxide synthase, a product of a hypoxia sensitive gene, in the cortex and medulla in dogs with unilateral ureteral obstruction for 21 hours. MATERIALS AND METHODS: Hemodynamic and clearance experiments were performed after release of ureteral obstruction in 6 dogs with unilateral ureteral obstruction, followed by Western blot analysis of nitric oxide synthase and immunohistochemistry. RESULTS: Ureteral obstruction raised mean ureteral pressure plus or minus standard error to 35.0 +/- 7.2 mm. Hg. In dogs with unilateral ureteral obstruction mean renal blood flow was 116 +/- 10 ml. per minute, lower than the 213 +/- 22 ml. per minute in sham operated dogs (p <0.01). After unilateral ureteral obstruction release the mean glomerular filtration rate was 9.5 +/- 2.1 ml. per minute, lower than the 27.3 +/- 1.8 ml. per minute in the contralateral unobstructed kidney (p <0.01). Western blot analysis showed that mean nitric oxide synthase/beta-actin in the cortex of the obstructed kidney was 0.04 +/- 0.01 densitometry units, lower than 0.11 +/- 0.02 densitometry units in the unobstructed contralateral kidney (p <0.05). In contrast, mean nitric oxide synthase/beta-actin in the medulla of the obstructed kidney was 1.29 +/- 0.33 densitometry units, greater than the 0.34 +/- 0.03 densitometry units in the unobstructed kidney (p <0.05). Immunohistochemistry revealed that the increased expression of nitric oxide synthase protein was localized to the endothelium of the vasa recta. CONCLUSIONS: Unilateral ureteral obstruction enhances nitric oxide synthase expression in the medulla but not in the cortex. This increased expression in the medulla may be the result of increased medullary hypoxia in unilateral ureteral obstruction, possibly contributing to medullary hyperemia after unilateral ureteral obstruction release.     

Enhanced expression of nitric oxide synthase in the early stage after increased pulmonary blood flow in rats.

OBJECTIVE: Evidence that vasodilator nitric oxide mediates normal pulmonary vascular tone has led to the hypothesis that endothelial injury induced by congenital heart disease with increased pulmonary blood flow disrupts these regulatory mechanisms and its associated altered vascular reactivity. Therefore, we hypothesized that increased pulmonary blood flow results in altered expression of endothelial nitric oxide synthase (eNOS). METHODS: We created an arteriovenous shunt in female Wistar (5-week-old) and measured the change of pulmonary blood flow and pressure immediately after and 1 month after the shunt operation. The protein levels of eNOS in the lung tissues of rats were assessed. RESULTS: The shunt immediately resulted in a significant increase in pulmonary blood flow (16.5 +/- 11.8% , pulmonary artery pressure (2.3 +/- 0.7 mm Hg), and blood O(2) saturation (16.1 +/- 11.8%) in the pulmonary artery. After 4 weeks, there was a significant increase in pulmonary blood flow (30.7 +/- 1.6%), pulmonary artery pressures (4.3 +/- 1.1 mm Hg), and blood O(2) content (43.3 +/- 17.5%). Western blot analysis demonstrated that eNOS protein was increased in the shunt lung 72 h after surgery and recovered to the control level 1 week later. CONCLUSION: This simple shunt model can induce early upregulation of eNOS expression with increased pulmonary blood flow and pulmonary artery pressure in rats.     

一氧化氮和米力农联合应用改善Fontan术后肺循环阻力的疗效

目的 探讨一氧化氮(iNO)与米力农联合应用能否进一步改善肺循环,并降低iNO撤离后反跳发生率.方法 31例改良Fortran术后跨肺压(TPG)>10mm Hg,动脉氧饱和度(sato2)<0.85者,随机分iNO组(iNO 10ppm吸入)15例和iNO+MIL组(iNO 10 ppm吸入后1 h启用米力农0.5 μg·kg-1·min-1静脉维持)16例.比较二组治疗后血流动力学、动脉氧饱和度及NO撤离的反跳发生率.结果 iNO+Mil组与iNO组相比治疗后中心静脉压(CVP)降幅[19.6±3.5)%对(15.2%±4.6)%,P<0.05]、TPG降幅[(18.2±4.8)%对(15.3±2.6)%,P<0.05]、动脉收缩压(SAP)升幅[(8.79±2.7)%对(5.2±3.1)%,P<0.05]和SatO2升幅[(9.3±3.2)%对(6.8±2.8)%,P<0.05]差异有统计学意义.iNO+Mil组NO撤离后反跳发生率明显降低,为1/16例,而iNO组为6/15例,组间差异有统计学意义,P<0.05.结论 一氧化氮与米力农联合应用较单纯NO治疗更进一步改善Fortran术后的肺循环阻力.     

Nitric Oxide Modulation of Pulmonary Blood Flow Distribution in Lobar Hypoxia

Background: Nitric oxide, endogenously produced or inhaled, has been shown to play an important role in the regulation of pulmonary blood flow. The inhalation of nitric oxide reduces pulmonary arterial pressure in humans, and the blockade of endogenous nitric oxide production increases the pulmonary vascular response to hypoxia. This study was performed to investigate the hypothesis that intravenous administration of an nitric oxide synthase inhibitor and regional inhalation of nitric oxide can markedly alter the distribution of pulmonary blood flow during regional hypoxia.

Methods: Hypoxia (5% Oxygen2) was induced in the left lower lobe of the pig, and the blood flow to this lobe was measured with transit-time ultrasound. Nitric oxide was administered in the gas ventilating the hypoxic lobe and the hyperoxic lung regions with and without blockade of endogenous nitric oxide production by means of Nomega -nitro-L-arginine methyl ester (L-NAME).

Results: Hypoxia in the left lower lobe reduced blood flow to that lobe to 27 plus/minus 3.9% (mean plus/minus SEM) of baseline values (P < 0.01). L-NAME caused a further reduction in lobar blood flow in all six animals to 12 plus/minus 3.5% and increased arterial oxygen tension (Pa sub O2) (P < 0.01). Without L-NAME, the inhalation of nitric oxide (40 ppm) to the hypoxic lobe increased lobar blood flow to 66 plus/minus 5.6% of baseline (P < 0.01) and, with L-NAME, nitric oxide delivered to the hypoxic lobe resulted in a lobar blood flow that was 88 plus/minus 9.3% of baseline (difference not significant). When nitric oxide was administered to the hyperoxic lung regions, after L-NAME infusion, the blood flow to the hypoxic lobe decreased to 2.5 plus/minus 1.6% of baseline and PaO2 was further increased (P < 0.01).     

The pathophysiology of pulmonary hypertension in congenital heart disease

Congenital heart disease with increased pulmonary blood flow commonly leads to the development of pulmonary hypertension and increased vascular reactivity. These serious sequelae are associated with the following two major categories of congenital heart defects: those resulting in increased pulmonary blood flow and increased pulmonary arterial pressure and those resulting in increased pulmonary venous pressure. Recent evidence that the pulmonary vascular endothelium is an important determinant of vascular tone has led to the hypothesis that endothelial injury, secondary to congenital heart disease with increased pulmonary blood flow, disrupts these regulatory mechanisms and thereby plays a role in the development of pulmonary hypertension and its associated increased vascular reactivity. In many animal models, endothelial dysfunction is a precursor for smooth muscle dysfunction, and there is an apparent progression from endothelial dysfunction to smooth muscle dysfunction as vascular changes progress. We established a chronic model of pulmonary hypertension with increased pulmonary blood flow in young lambs by placing a systemic-to-pulmonary shunt in utero. In this model, we found significant physiologic and molecular alternations of both the nitric oxide (NO) and endothelin signaling pathways, two important mechanisms by which the endothelium regulates pulmonary vascular tone. These alterations occur extremely early and precede severe anatomic changes. Early endothelial damage may contribute to the development of pulmonary hypertension and its associated enhanced pulmonary vascular reactivity.     

核素肺灌注显像对瓣膜性心脏病合并肺动脉高压病人的手术疗效观察

目的 探讨采用首次通过法核素肺灌注显像、通过放射性时间-计数曲线方法了解瓣膜性心脏病合并有肺动脉高压(PH)手术前、后肺动脉压力的变化规律的价值.方法 115例二尖瓣病变为主的瓣膜性心脏病病人均行瓣膜置换或成形术治疗.所有病人在手术前,手术后7天行核素肺灌注显像检查,33例在术后3个月进行第3次复查.另选10名健康者,测其肺循环平均时间(LET)作为正常对照组.结果 与术前相比,术后7天LET明显降低(P<0.001).33例术后3个月的LET与术后7天差异虽无统计学意义,但LET仍有继续下降趋势.结论 瓣膜性心脏病合并有PH病人,肺动脉压力的降低在术后7天左右最明显,此后降低缓慢.术前肺动脉压力越高,在术后早期越难以降至正常水平.无创性核素肺灌注显像检查方法在瓣膜性心脏病合并PH的术前判定、手术疗效和预后判断等方面有明显的优点和实用价值.     

垂体后叶素对心肺转流后低血压患者冠状动脉血流量的影响

目的 评估垂体后叶素对心肺转流(cardiopulmonary bypass,CPB)术后低血压患者冠状动脉血流量的影响.方法 行心脏瓣膜置换术CPB后发生低血压患者24例,静脉注射小剂量垂体后叶素负荷量0.6 U,随后以1 U/h～4 U/h泵入维持.连续监测并记录麻醉诱导后CPB前(T1)、CPB停机后给予垂体后叶...     

肺动脉内膜剥脱术治疗慢性栓塞性肺动脉高压——UCSD32例手术经验

目的 分析肺动脉内膜剥脱术(PEA)治疗慢性栓塞性肺动脉高压的围手术期资料,探讨美国加州大学圣迭戈分校(UCSD)手术经验.方法 回顾性研究UCSD 32例肺动脉血栓内膜剥脱手术资料,其中男17例,女15例;平均年龄(47.56±16.04)岁,平均病程(3.90±4.61)年;15例有深静脉血栓病史.采用全麻、胸骨正中切口、深低温、间断停循环双侧肺动脉内膜剥脱的手术方法.结果 根据术中病理标本Jamieson分型,Ⅰ型占21.8%,Ⅱ型占28.1%,Ⅲ型占37.5%.平均转机(236.32±37.27)min,主动脉阻断(111.69±28.14)min,停循环(38.00±13.58)min.术后机械通气(66.23±99.24)h,住ICU(4.62±4.50)天,无死亡.病人肺动脉收缩压由术前(81.03±16.92)mm Hg(1 mm Hg=0.133 kPa)降至术后(51.20±12.16)mm Hg,肺血管阻力由术前(88.91±42.32)kPa·s·L-1降至术后的(34.38±15.68)kPa·s·L-1,心排量由术前(3.65±1.08)L/min增加到术后(5.85±1.21)L/min,中心静脉压由(13.07±2.11)cmH2O(1 cmH2O=0.098 kPa)降至(9.86±3.02)cmH2O.术后短期随访显示,病人心功能(NYHA)恢复到Ⅰ级19例、Ⅱ级13例,生活质量明显改善.结论 PEA是治疗慢性栓塞性肺动脉高压的重要手段,手术成功率逐年提高;深低温、间断停循环、双侧肺动脉内膜剥脱及内膜外翻技术为PEA标准术式.多中心资料证实该术式可以有效降低肺动脉压和肺血管阻力,明显改善血流动力学指标和心肺功能.多数国内医疗中心没有足够手术经验,应尽量避免选择肺动脉压收缩≥100mmHg,肺血管阻力≥100kPa·s·L-1及Ⅲ型病变者行PEA手术.     

含乌司他丁低温肺保护液在法洛四联症体外循环术中的应用

目的 探讨含乌司他丁(UTI)的低温肺保护液对婴幼儿法洛四联症体外循环肺内炎性反应的保护作用.方法 30例行法洛四联症(TOF)根治术病婴,随机分为肺保护组和对照组,各15例.术前有感染征象(白细胞>12×109/L、体温>38℃,C-反应蛋白>8 mg/L)、有过敏史者除外.肺保护组心脏停跳同时肺动脉灌注低温肺保护液,对照组常规行TOF根治术.围术期监测血浆肿瘤坏死因子(TNF-α)、中性粒细胞CD11b的表达和髓过氧化物酶(MPO),同时监测血气、肺功能及临床指标.结果 血清TNF-α水平肺保护组较对照组低,关胸后0、3 h差异有统计学意义,(11.15±2.47)pg/ml对(14.21±5.55)pg/ml、(12.01±2.69)pg/ml对(15.94±4.86)pg/ml.肺保护组新鲜全血中性粒细胞表面的CD11b平均荧光强度(MFI)水平关胸后3、6 h显著低于对照组,(126.23±36.05)对(156.98±48.34)、(137.27±38.85)对(173.27±67.43).肺保护组MPO水平关胸后3、6、24 h显著低于对照组,(156.52±17.57)U/L对(178.45±35.68)U/L、(178.28±23.63)U/L对(224.66±49.66)U/L、(130.52±57.50)U/L对(96.50±14.49)U/L.肺保护组呼吸机辅助时间明显较对照组短,(17.60±6.39)h对(23.70±8.51)h.肺保护组肺泡-动脉氧阶差(A-aDO2)在关胸后3、6 h显著低于对照组(120.92±33.08)mm Hg(1 mm Hg=0.133 kPa)对(145.52±39.38)mm Hg、(74.76±40.16)mm Hg对(112.50±44.16)mm Hg.肺动态顺应性(Cdyn)在关胸后3、6 h肺保护组显著高于对照组(0.59±0.11)ml·cmH2O-1·kg-1对(0.46±0.17)ml·cmH2O-1·kg-1、(0.67±0.09)ml·cmH2O-1·kg-1对(0.53±0.18)ml·cmH2O-1·kg-1.结论 肺动脉灌注含乌司他丁的低温肺保护液明显减轻体外循环术后肺的炎性反应,具有肺保护作用.