瑞舒伐他汀对右心衰竭幼鼠右心功能的影响

目的观察瑞舒伐他汀对野百合碱致右心衰竭SD幼鼠血流动力学及心肺病理的影响。方法清洁级SD雄性幼鼠140只,体质量90~100 g,随机分为4组,G1、G2、G3及G0对照组,每组各35只幼鼠,G1、G2、G3组幼鼠按50 mg/kg剂量,一次性腹腔注射野百合碱(MCT)溶液,G0组予等体积生理盐水一次性腹腔注射,同时G2组予瑞舒伐他汀片5mg/(kg.d)灌胃,G3组从第5周始予瑞舒伐他汀片5mg/(kg.d)灌胃。注射MCT后每2周选取5只幼鼠,采用彩色多普勒超声仪测定幼鼠右室横径、三尖瓣反流速度及肺动脉压力,随后处死大鼠,取心脏、肺组织做病理切片对比观察。结果除第2周外,第4、第6周时各组幼鼠的右室横径、三尖瓣反流速度、肺动脉压力的差异均有统计学意义(P<0.01)。G1组幼鼠心肺组织病理切片可见中小动脉中膜明显增厚和小动脉肌化,部分肺组织远端小动脉闭塞,肺泡内可见心衰细胞,右室心肌细胞肥大伴纤维组织增生,炎细胞浸润明显。G2、G3组与G1组幼鼠相比病理变化较轻,其中G2组接近正常。结论瑞舒伐他汀可减缓幼鼠肺动脉高压致右心衰竭的进展过程。     

血栓调节蛋白在野百合碱诱导肺动脉高压大鼠血浆及肺组织中的变化

不同原因引起的肺动脉高压（简称肺高压）都具有共同的特征性病理改变,即血管收缩、血管重塑及原位血栓形成。血栓调节蛋白（TM）是机体中最重要的抗凝因子,在维持正常凝血功能及维持血液的流动性等方面发挥重要作用。研究发现肺高压时血浆TM水平降低,提示TM可能在肺高压形成过程中发挥作用。     

野百合碱致右心衰竭幼鼠Connexin43的变化及卡托普利和坎地沙坦的干预作用

目的 探讨Connexin43(Cx43)在野百合碱(MCT)致右心衰竭幼鼠中的变化及卡托普利和坎地沙坦的干预作用.方法　50只SD幼鼠腹腔注射MCT诱发肺动脉高压(PAH),随机分为心衰4周组(E1组)、心衰6周组(E2组)、卡托普利组(C1组)、坎地沙坦组(C2组)和二药联合组(C3组).另20只幼鼠腹腔注射9 g·L-1盐水作为对照,分为正常对照4周组(N1组)和正常对照6周组(N2组).测定每组存活幼鼠的血流动力学和相关生理指标,采用ELISA法检测其血清Cx43水平,免疫组织化学法和 RT-PCR法测定其右心室心肌组织Cx43和Cx43 mRNA的表达.结果　E1组与N1组比较,右心室肥厚指数、中心静脉压(CVP)、右心室收缩压 (RVSP) 显著升高,右心室压最大上升速率 (RVdp/dt) 显著降低,右心室心肌细胞排列紊乱、肌浆溶解,并可见空泡变性,右心衰竭模型成功.E1组血清Cx43水平、右心室心肌组织Cx43和Cx43 mRNA均较N1组降低.E2组与N2组比较,CVP、RVSP显著增高,RVdp/dt显著降低,血清Cx43水平、右心室心肌组织Cx43蛋白和Cx43 mRNA均降低.E2组与E1组比较,右心室肥厚指数、CVP、RVSP持续增高,RVdp/dt持续降低,E2组血清Cx43、右心肌组织Cx43蛋白和Cx43 mRNA进一步降低.C1组、C2组与E2组比较,血流动力学改善,右心室肥厚减轻,血清Cx43水平、右心肌组织Cx43蛋白和Cx43 mRNA均增高.C1组、C2组分别与C3组比较,血流动力学、血清Cx43水平、右心室心肌组织Cx43蛋白和Cx43 mRNA表达比较差异均无统计学意义.结论　PAH致右心衰竭时,Cx43参与心力衰竭的发生发展,随着心力衰竭的加重,其表达进一步降低;Cx43在幼鼠血清、右心室心肌组织中的水平具有一致性;卡托普利或坎地沙坦可能通过促进Cx43的表达缓解压力负荷性右心衰竭,二者比较无明显差异,联合用药并不能提高疗效.     

野百合碱诱导肺动脉高压大鼠肺动脉Ⅰ型胶原的变化

目的研究野百合碱(MCT)诱导肺动脉高压(PH)大鼠肺动脉Ⅰ型胶原的变化,探讨肺血管结构重建的机制。方法雄性Wistar大鼠12只,随机分为MCT组(n=6)和对照组(n=6)。MCT组腹腔注射MCT(60 mg.kg-1,第1天),对照组注射同等剂量9 g.L-1盐水。实验3周后,测定各组平均肺动脉压(mPAP)、右心室/(左心室+室间隔)比值[RV/(LV+S)]、大鼠体质量;光镜下观察其肺组织HE染色结果,免疫组织化学法检测其肺动脉Ⅰ型胶原蛋白的表达,并进行定位和半定量分析。应用SPSS 13.0软件进行统计学分析。结果与对照组比较,MCT组大鼠mPAP及RV/(LV+S)显著升高[mPAP:(10.60±2.06)mmHg(1 mmHg=0.133 kPa)vs(32.40±3.24)mmHg,P<0.01;RV/(LV+S):0.28±0.04vs0.47±0.10,P<0.01],体质量显著减低[(291.4±11.6)gvs(252.7±6.8)g,P<0.01];光镜下可见MCT组大鼠肺动脉血管内皮细胞出现肿胀、坏死、脱落;肺动脉平滑肌明显增生,管壁明显增厚,管腔狭窄,甚至闭塞,肺血管结构发生...     

韧粘素与大鼠野百合碱性肺高压肺血管重建的相关性研究

目前已知 ,肺血管重建是不同原因肺高压的共同病理特征。韧粘素 (ｔｅｎａｓｃｉｎ ,ＴＮ)是一种大分子细胞外基质蛋白 ,它参与血管的重建过程[1] 。本研究通过快速竞争性ＲＴ ＰＣＲ技术及免疫组化和图像分析方法 ,观测野百合碱性肺高压大鼠肺组织及肺动脉中ＴＮｍＲＮＡ的动态表达水平和ＴＮ蛋白的沉积、分布情况及其与血管平滑肌细胞增殖、迁移的关系 ,以期阐明ＴＮ在肺高压肺血管重建中的作用。材料和方法雄性ＳＤ大鼠 72只 ,随机均分为野百合碱 (ＭＣＴ)组和正常对照 (ＣＯＮ)组。ＭＣＴ组大鼠以 2 %野百合碱液按 6 0ｍｇ/ｋｇ剂量在背…     

弹性蛋白酶抑制剂对野百合碱诱导的肺动脉高压干预作用的研究

目的　探讨丝氨酸弹性蛋白酶抑制剂ZD 0 892对野百合碱性肺动脉高压的逆转作用。方法　利用野百合碱建立大鼠肺动脉高压模型。 2 1天后 ,治疗组给予ZD 0 892管饲 ,剂量按2 4 0mg/(kg·d)分 2次给予 ,模型组按同样剂量管饲ZD 0 892的溶媒 ;而正常对照组管饲同样剂量的生理盐水。于实验第 2 1、2 8、35天 ,使用荧光分光光度计检测肺动脉弹性蛋白的离解活性 ,通过右心导管法测定肺动脉压力 ;并在上述时间点 ,采用钡明胶灌注的技术对周围肺动脉进行组织病理学分析。结果　注射野百合碱后的 2 1天 ,大鼠肺动脉高压已经形成 ,肺动脉弹性蛋白酶的活性明显升高。经ZD 0 892治疗 1周后 ,肺动脉弹性蛋白酶的活性显著下降 ,肺动脉压力、周围肺动脉的肌化数、肌性肺动脉的中膜厚度也相应减低 ;治疗 2周后 ,弹性蛋白酶的活性降低至正常水平 ,肺动脉压力及结构也随之恢复正常。结论　内源性血管弹性蛋白酶在肺动脉高压的发生及发展中起重要作用 ,ZD 0 892能有效地抑制其活性 ,进而可使野百合碱诱导的严重肺动脉高压完全逆转。     

肺动脉高压大鼠模型肺血管维甲酸受体的变化

目的阐明维甲酸受体(retinoic acid receptor,RAR)变化与肺动脉高压发病机制的关系,并评价全反式维甲酸(all-trans retinoic acid,atRA)对肺高压肺血管重建过程的逆转作用。方法选择3周龄SD大鼠72只,将其平均分为3组,试验组1为野百合碱(Monocrotaline,MCT)诱导建立SD大鼠肺动脉高压模型;试验组2为MCT诱导建立SD大鼠,同时给予atRA 10 mg/(kg.d)灌胃;对照组为生理盐水组。分别于实验第7、14、21、28天每组取6只大鼠,测肺动脉压力后处死;实时定量RT-PCR检测主动脉、肺动脉及肺组织中RAR受体数量与mRNA水平。结果肺动脉高压时,肺血管中RAR各亚型(α、β、γ)转录水平均有下降,且随肺动脉高压加重下降更为明显。结论 RAR可能参与了肺动脉高压的发病机制。     

野百合碱诱导大鼠肺高压时韧粘素mRNA表达水平的动态变化

目的：观察野百合碱(MCT)所致肺高压大鼠肺组织和肺动脉中韧粘素(TN)mRNA的动态表达水平,探讨其与肺高压肺血管重建的关系。方法：SD大鼠随机分为MCT组和正常对照组(CON),采用野百合碱皮下注射法诱导建立大鼠肺高压模型,并通过快速竞争性RT PCR技术检测不同时间点(给药后第7,14,21,28天)大鼠肺组织和肺动脉中TNmRNA的表达水平。结果：TN mRNA水平在给药后第7天即有上调,CON组肺组织TNmRNA为0.29±0.04,MCT组为0.56±0.08,两组间差异有显著性(P<0.01);CON组肺动脉TN mRNA 为0.30±0.04,MCT组为0.57±0.05,两组间差异有显著性(P<0.05)。TN mRNA水平上调早于肺动脉压的升高,随压力上升和时间延长TN mRNA继续增高。结论：TN参与了肺高压肺血管重建过程,在肺高压发病中可能具有重要作用。     

Cardiac atrial natriuretic peptide in monocrotaline-induced pulmonary hypertensive rats

To determine the time course and potential triggers for synthesis of atrial natriuretic peptide (ANP) in right ventricle during the development of right ventricular hypertrophy (RVH), we measured mean right atrial pressure, right ventricular systolic pressure (RVSP), immunoreactive ANP (iANP) concentrations in plasma, and cardiac iANP concentrations and contents of monocrotaline (MCT)-induced pulmonary hypertensive rats treated with a subcutaneous injection of MCT (40 mg/kg). Following the development of RVH and pulmonary hypertension, iANP concentrations in plasma and iANP concentrations and contents in ventricular tissues increased with time. At the third week after treatment, iANP concentrations in MCT rats increased 6-fold in plasma, 57-fold in the right ventricular free wall, 20-fold in the ventricular septum and 10-fold in the left ventricular free wall compared with those in controls. At the third week, iANP contents of total ventricular tissues in MCT and control rats were 29% and 0.8%, respectively, of the corresponding atrial contents. The iANP concentrations and contents of right ventricular free walls in MCT rats were greater than those of any other parts of ventricular tissues. The iANP concentrations in right ventricular free walls were very closely related to RVSP (r = 0.93, P < 0.001). In MCT rats, iANP concentrations in right atrial tissues decreased with time. This study shows that ventricular ANP contributes to the amount of ANP stored within the heart in MCT rats and that pressure overload may be one of the triggers for ANP synthesis in the right ventricle.     

�ζ�����ѹ����Ѫ��N����������ǰ���������Teiָ��������о�

??Abstract??Objective To investigate the correlation among plasma N-terminal pro-brain natriuretic peptide ??NT-proBNP?? and right ventricular Tei ??RVTei?? and right ventricular fractional area change ??RVFAC?? in children with pulmonary hypertension. Methods From January 2007 to November 2012??echocardiography and serological examination data of 38 patients from Samsung Seoul Hospital in Korea were retrospectively analyzed. Patients were divided into two groups ??16 cases with 30??PASP??70mmHg ??mild to moderate?? and 22 cases with PASP≥70mmHg ??severe??. Results ??1??RVFAC?? PASP and plasma concentration of NT-proBNP had a statistically significant difference??P??0.05?? between mild to moderate PAH group and severe PAH group . RVTei index had no difference between the two groups??P??0.05??. ??2??Correlation analysis??the plasma concentration of NT-proBNP had a positive correlation ??r = 0.544??P??0.05??with PASP??a negative correlation??r = -0.767??P??0.05??with RVFAC??RVFAC had a negative correlation??r = -0.711??-0.767??P??0.05?? with PASP and the plasma concentrations of NT-proBNP?? the RVTei had no correlation with the plasma concentration of NT-proBNP?? PASP or RVFAC??r = -0.041??-0.048??0.016??P??0.05??. Conclusion Whether there are correlations between the plasma concentration of NT-proBNP and RVFAC depends on the degree of PAH. This suggests that the plasma concentration of NT-proBNP and RVFAC can be used as evaluation of right ventricular function in children with pulmonary hypertension.     

先天性心脏病肺动脉高压手术前后右心功能变化和治疗

目的 了解先天性心脏病左向右分流导致的重度肺动脉高压对右心功能的影响以及手术矫治后右心功能的恢复状态。方法 对室间隔缺损(室缺)合并重度肺动脉高压(全肺循环阻力增加)的40例患儿，用心导管的方法进行术前、术后5～7年右心功能、肺循环的血流动力学随访测定。结果 术前右心心搏指数、作功指数、心排指数显著高于术后；术前右房压、右室收缩压及舒张压、肺动脉压力和阻力均增高，缺损修补后右室舒张压恢复正常，收缩压的降低与肺动脉压力下降有关；大型室缺左向右分流重度肺动脉高压右心功能不全系继发性右室高排出量心力衰竭，且伴有舒张功能障碍。结论 治疗心力衰竭不宜首选正性心肌收缩药物；降低肺动脉压力、减少左向右分流、根治心内畸形是合理的选择；术后右室收缩压持续不能恢复至正常水平，提示继发性肺血管梗阻性病变存在。     

肺动脉高压时EVE动态变化及与肺血管重建过程关系的实验研究

为探讨肺动脉高压时内源性血管弹性蛋白酶 (EVE)的动态变化及其与肺血管重建之间的关系 ,利用野百合碱建立大鼠肺高压模型 ,于实验第2、8、14、21天 ,使用荧光分光光度计检测肺动脉的弹性蛋白离解活性 ,通过右心导管法测定肺动脉压力 ;并在上述时间点 ,对周围肺动脉进行组织病理学分析。结果显示 ,肺动脉的弹性蛋白离解活性在注射野百合碱后的第2天即明显升高(3.87±0.45) ,第8天降为正常 (0.18±0.02) ,第14天再次出现升高现象 (1.45±0.18) ,并一直持续到第21天(1.91±0.22) ;而肌性肺动脉的比例增加在注射野百合碱后第8天出现(32.67±4.23) ,肺动脉中膜的增厚 (4.20±0.37)及肺动脉压力的增高 (21.00±2.10)在第14天后出现。提示EVE活性的早期升高可能是肺动脉高压的一种重要触发因素 ;EVE活性的第2次升高可能与肺高压的进展有关     

缺氧性肺动脉高压新生儿右心室功能的组织速度多普勒超声研究

目的 探讨组织速度多普勒成像(TVI)技术评价缺氧性肺动脉高压(HPH)新生儿右心室功能的价值.方法 35例HPH患儿及28例正常新生儿于生后3 d应用超声心动图测量肺动脉收缩压(PASP),用传统超声技术测定右室射血分数(RVEF)值、右心室舒张早期峰值(E峰)、舒张晚期峰值(A峰)、E/A值,同时以TVI技术测量三尖瓣环指标(收缩期波Sa、舒张早期波Ea、舒张晚期波Aa、Ea/Aa值).结果 HPH组三尖瓣环Sa、Ea、Ea/Aa及RVEF值较对照组减低(t=2.67～4.69,P均<0.01).HPH组的右心室E/A值较对照组减低,但差异无统计学意义.HPH组的三尖瓣环Sa与RVEF值呈正相关(r=0.451,P<0.05).结论 HPH新生儿的右心室舒张、收缩功能减低,TVI技术与传统超声技术结合能更敏感地发现右心室功能变化.     

Dependence of canine right coronary arterial flow upon heart rate and right ventricular pressure

There is a paucity of knowledge regarding right coronary pulsatile hemodynamics when the right ventricle is under hemodynamic overload as is often the case in pediatric patients with congenital cardiac anomalies. To elucidate the exact mechanisms for the right coronary artery (RCA) to cope with the overload, we studied nine open-chest adult Beagles and analyzed the flow signals of the RCA in relation to independently varied heart rate (pacing) and right ventricular pressure (pulmonary artery banding). Both increased heart rate and right ventricular pressure increased the total volume flow of the RCA. The diastolic over total flow ratio (D/T), however, enlarged on increasing right ventricular pressures while it declined on increasing heart rates. Our data confirmed, as well, that increased flow of RCA on rising heart rate was provided mainly by an increase in systolic phase, while the increase on augmented right ventricular pressure was provided by the increase in diastolic phase. The RCA manages to deliver blood to the right ventricular musculature in two different ways in response to increasing heart rate and right ventricular pressure.     

Effects of heart rate and right ventricular pressure on right coronary arterial flow and its systolic versus diastolic distribution in a variety of congenital heart diseases in children

BACKGROUND AND METHODS: In order to elucidate the underlying adjusting mechanism of human right coronary arterial (RCA) flow to increased right ventricular pressure (RVP) in children, we recorded RCA flow velocity in 24 pediatric cardiac patients at the orifice of its main trunk at the time of heart catheterization using the Doppler guidewire. RESULTS: The ratio of diastolic flow (DF)/total flow (TF), or the proportion of the DF time integral over a total of one cardiac cycle, had a negative correlation with heart rate (HR; r = -0.58, n = 11) in children with normal right ventricular systolic pressure (RVSP; RVSP < 35 mmHg). In contrast, the DF/TF ratio had a good correlation (r = 0.88, n = 24) with RVSP in all patients under study. The ratio of diastolic area (DA)/total area (TA), defined as the ratio of an area encircled by the aortic pressure curve above and the RVP curve below for diastole, over a total of one cardiac cycle, representing the overall effect of both HR and transcoronary pressure difference, also correlated well (r = 0.89, n = 24) with DF/TF. Total volume flow of the RCA also increased (r= 0.76, n = 24) with increases in RVSP, first by an increase in flow velocity through the RCA, during both systole and diastole, then by widening of the RCA lumen at very high pressures. These changes were initially more dependent on diastole with increasing RVSP because: (i) of a more marked augmentation of flow velocity in diastole compared with systole; and then (ii) of a significant decrease in flow velocity in systole at very high pressures. CONCLUSIONS: We clarify how the RCA manages to increase flow through it at different HR as a function of chronic RVP overload in pediatric cardiac patients.     

法舒地尔对大鼠低氧性肺动脉高压及其右心室肥厚的影响

目的 探讨Rho激酶抑制剂法舒地尔对大鼠低氧性肺动脉高压(HPH)及其右心室肥厚的影响.方法　雄性SD大鼠24只随机分为对照组、模型组和法舒地尔干预组(干预组).采用常压间断低氧法建立大鼠HPH模型.测定各组大鼠平均肺动脉压力(mPAP)、右心室肥厚指数(RVHI);透射电镜观察各组右心室心肌细胞超微结构变化.应用SPSS 11.0软件进行统计学分析.结果 模型组大鼠mPAP、RVHI分别为(31.38±1.98) mmHg(1 mmHg=0.133 kPa)、0.47± 0.03,均明显高于对照组大鼠[(15.25±0.91) mmHg、0.25±0.02](Pa＜0.01);透射电镜显示对照组心肌细胞及毛细血内皮呈正常结构,模型组大鼠右心室心肌细胞线粒体明显增多、肿胀,嵴模糊、消失,心肌肌丝明暗带不清晰.干预组大鼠mPAP、RVHI分别为(16.63±1.53) mmHg、0.27±0.02,均显著低于模型组(Pa＜0.01).干预组大鼠右心室心肌细胞及毛细血管内皮基本正常.结论　法舒地尔对低氧所致的肺动脉高压、右心室肥厚及其心肌细胞损伤大鼠具有较好的预防和逆转作用.     

超声心动图评价心力衰竭患儿左、右心舒张功能

目的　探讨充血性心力衰竭（ＣＨＦ）患儿左、右心舒张功能及其相互关系。方法　对５１ 例ＣＨＦ患儿和６０ 例正常对照儿童用多普勒超声心动图测量左、右室充盈参数。结果　与正常对照组比较,ＣＨＦ组患儿左、右室充盈参数均显示舒张受损,且左、右室充盈参数呈良好相关。结论　ＣＨＦ组患儿均存在左、右心舒张功能障碍,且程度类型相似