伊洛前列环素对肺高压患者血流动力学及BNP分泌的影响
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摘要
背景：肺动脉高压(Pulmonary arterial hypertension, PAH)是一种进展性的疾病,主要特征是肺血管阻力进行性升高,最终导致患者右心衰竭而死亡。右心衰竭是所有类型肺动脉高压患者致残、致死的共同途径,而肺动脉高压也是右心衰竭的最主要原因。脑钠肽(Brain natriuretic peptide, BNP)主要从心室肌细胞分泌,在心室容积负荷和室壁张力增加时快速合成并分泌入血,多项研究表明BNP是一个反映心功能紊乱的敏感而特异的指标。伊洛前列环素作为一种人工合成的前列环素类似物,通过雾化吸入具有良好的选择性肺血管扩张作用,是一种有前景的控制肺动脉高压的方法。
目的：本研究的目的是分别检测肺动脉高压患者不同部位(股静脉、右心房、右心室、左心室、股动脉)BNP的分泌情况,以及急性肺血管扩张试验在吸入伊洛前列环素后对肺动脉高压患者血流动力学及BNP分泌的影响。
方法：选择2008年至2010年期间收住我院,经心脏彩超检查疑诊PAH患者13例(10例女性,3例男性,平均年龄43.8岁)。入院后收集基线资料(血常规、血生化、心电图、胸片、经胸超声心动图)；行6分钟步行距离(6 Minute Walk Distance,6MWD)测试及Borg呼吸困难评分；右心导管检查测定肺动脉收缩压(PASP)、肺动脉平均压(mPAP)及舒张压、右房压(RAP)、右室压(RVP)及舒张末压,并分段取血测血氧饱和度(上腔静脉、下腔静脉、肺动脉、右心房、右心室、股动脉)以计算心排出量(CO)、心脏指数(Cl)、全肺阻力(TPR)；行左心导管测定左室舒末压。分段取血测定BNP浓度(股静脉、右心房、右心室、左心室、股动脉)。后雾化吸入伊洛前列环素20μg,吸药时间15分钟,30分钟后再次测定以上血流动力学参数并再次取各部位血液测定BNP浓度。比较吸药前后血流动力学及BNP分泌的变化。BNP检测方法：使用博适-Triage干式快速定量心肌梗死/心力衰竭诊断仪(美国Biosite公司产品)。采集全血1-2ml加入EDTA抗凝试剂管,摇匀,样品保持在室温下并在4小时内进行检测。取250μl EDTA抗凝全血加入Triage检测板,将检测板放入心力衰竭诊断仪内,15min内自动打印结果。
结果：13例患者资料完整获取。1.经胸超声心动图(TTE)测量PAH患者右房、右室增大,PASP升高,BNP、UA血浆水平增加,PAH心功能分级、Borg呼吸困难评分增加。6MWD与右房平均压、右室舒末径、PAH分级明显负相关。多元回归分析发现,右室舒末径、PAH心功能分级与6MWD负相关2.雾化吸入伊洛前列环素后,右房平均压(mRAP)、右室平均压(mRVP)、肺动脉收缩压(PASP)、肺动脉平均压(mPAP)、全肺阻力(TPR)下降,均具有统计学意义。心指数(CI)、混合静脉血氧饱和度(SvO2)上升,具有统计学意义。3.PAH患者BNP分泌增加,吸药前各部位BNP血浆水平比较左心室>股动脉>右心房>右心室>股静脉,但各部位差异未达到统计学意义。吸药前股静脉BNP浓度与右房平均压(mRAP)、右室平均压(mRVP)、右室舒末压、Borg呼吸困难评分、PAH心功能分级正相关,与6MWD呈负相关。多元回归分析发现,右房收缩压、右室平均压、PAH心功能分级与股静脉血浆BNP的水平相关。吸药前股动脉与右房平均压、右室平均压、右室舒末压、PASP、mPAP、Borg呼吸困难评分、PAH心功能分级正相关,与6MWD呈负相关。多元回归分析发现,右房收缩压与股动脉血浆BNP的水平相关。4.吸药后,各部位BNP血浆水平均下降,具体比较左心室>右心室>股动脉>右心房>股静脉,但各部位差异未达到统计学意义。右心房(P<0.05)、左心室(P<0.01)、股静脉(P<0.05)血浆BNP下降明显,差异有统计学意义。股动脉、右心室也有下降趋势,但未达统计学意义。吸药前,右房BNP分泌大于右室,而吸药后右室大于右房。
结论：1.6MWD、Borg呼吸困难评分、BNP血浆水平、UA、TTE指标及PAH心功能分级是评估PAH患者病情严重程度的有效指标。右心导管测得的右房压是诊断和评估PAH患者病情的重要指标,右心导管检查具有重要指导作用。2.吸入伊洛前列环素后,右房压、右室压、PASP、mPAP、TPR下降,CI、SvO2上升。表明吸入伊洛前列环素对PAH患者血流动力学有重要影响。3.PAH患者血浆BNP水平增加,各部位中以左室水平最高,提示可能存在左室心肌细胞分泌BNP直接入心腔的可能。在PAH患者中左室舒张功能也有一定程度受损,需进一步研究。4.吸入伊洛前列环素后对血浆BNP水平有影响,吸药后各部位BNP水平下降,且左心室、右心房、股静脉血浆水平下降明显。
Background:Pulmonary arterial hypertension (PAH) was a progressive disease characterized by progressive pulmonary vascular resistance increased, eventually leading to right heart failure and death. Right heart failure is a common pathway of death and disability in patients with all types of PAH, and PAH is also the main reason for right heart failure. Brain natriuretic peptide (BNP) is mainly secreted from the cardiac ventricular in response to ventricular volume expandion and pressure overload quickly. Studies showed that BNP would be an index for diagnose heart dysfunction with higher sensitivity and specificity than other natriuretic peptides. As an analogue of prostacyclin, nebulized iloprost have the favorable effect of selective vasodilation and may be a prospective agent to control the PAH.
Objective:The study is to explore the BNP secretion in different position (femoral vein, right atrium, right ventricle, left ventricle, femoral artery) of PAH patients, and the effect of hemodynamic parameters and the BNP plasma levels on acute pulmonary vasodilator test after iloprost inhalation.
Method:Randomly selected 13 cases from the patients hospitalized in our hospital from 2008 to 2010, all of them were diagnosed of pulmonary hypertension through Color Doppler. In these patients, there were 10 females and 3 males, mean age 43.8. After being admitted to hospital, we collected the baseline data (blood, blood biochemistry, electrocardiogram, chest X-ray, Transthoracic echocardiography); 6 minutes walk distance (6MWD) and Borg dyspnea rating (Borg scale); Determination of pulmonary artery systolic pressure (PASP), mean pulmonary artery pressure (mPAP), diastolic pulmonary artery pressure, right atrium pressure, right ventricular pressure and right ventricular end-diastolic pressure with right catheterization; Subsection blood oxygen saturation were measured (superior vena cava, inferior vena cava, pulmonary artery, right atrium, right ventricle) for calculation the pulmonary vascular resistance, cardiac output, cardiac index, total pulmonary resistance. With left catheterization, left ventricular end-diastolic pressure was detemined. Blood sample were measured for plasma BNP levels in different position (femoral vein, right atrium, right ventricle, left ventricle, femoral artery). All patients inhaled iloprost via nebulized aerosol at a dose of 20μg for 15min continuously, then the hemodynamic parameters and the plasma BNP levels were determined again. Measurement of BNP plasma levels:All samples were collected by puncture into ethylene diamine tetra acetic acid (EDTA) tubes. The blood samples were kept at room temperature and analyzed within 4h,250μl of the whole blood was added to the Triage BNP. Then the device was placed into the Triage Meter, which measures the fluorescence intensity of the BNP assay zone. The assay was completed in approximately 15min.
Results:13 patients have complete data acquisition.1. Both of the right atrium and ventricular were enlarged with Transthoracic echocardiography in PAH patients, PASP, BNP, Uric acid (UA), PAH heart functions class, Borg scale were increased. There were negative correlation between the 6MWD and mean right atrium pressure (r=-0.594, P<0.05), right ventricular end-diastolic diameter (r=-0.692, P<0.05), and PAH heart functions class (r=-0.843, P<0.01). Multiple regression analysis showed that right ventricular end-diastolic diameter, PAH heart functions class were independent determinants of 6MWD.2. After iloprost inhalation, the right atrium mean pressure, right ventricle mean pressure, PASP, mPAP, total pulmonary resistance were all significantly declined. Cardiac index, mixed venous oxygen saturation were both increased.3. The plasma BNP levels was in the patient with PAH before inhaling drug, the secretion level for plasma BNP were left ventricle> femoral artery> right atrium> right ventricle> femoral vein, but there were no statistical significance. Plasma BNP levels were significantly related with mean right atrium pressure, mean right ventricle pressure, right ventricle diastolic pressure, 6MWD, Borg scale, PAH heart functions class. Multiple regression analysis showed that there were positive correlation between the plasma BNP levels and RA systolic pressure or and RV mean pressure or and PAH heart functions class respectively.4. After iloprost inhalation, BNP secretion declined significantly in right atrium (P<0.05), femoral vein (P<0.05), left ventricle (P<0.05). Right ventricle and femoral artery had been a downward trend, but had no statistical significance. The BNP secretion of right atrium was more than right ventricle before inhalation, but after inhalation the latter more than the former.
Conclusions:1.6MWD, Borg scale, plasma BNP levels, PAH heart functions class, UA and join TTE were effective index to evaluate PAH patients'condition.2. Iloprost inhalation had important influence to PAH patients hemodynamic. After iloprost inhalation, right atrium pressure, right ventricular pressure, PASP, mPAP, total pulmonary resistance were decreased and cardiac index, mixed venous oxygen saturation were increased.3. BNP secreted was increased in PAH patients, and each part of the highest was left ventricular. This situation show that left ventricular also had certain degree of damage in PAH patients.4. Iloprost had influenced to plasma BNP levels. After iloprost inhalation, each part of plasma BNP levels had decreased and left ventricular, right atrium, femoral veins dropped significantly.
目的：本研究的目的是分别检测肺动脉高压患者不同部位(股静脉、右心房、右心室、左心室、股动脉)BNP的分泌情况,以及急性肺血管扩张试验在吸入伊洛前列环素后对肺动脉高压患者血流动力学及BNP分泌的影响。
方法：选择2008年至2010年期间收住我院,经心脏彩超检查疑诊PAH患者13例(10例女性,3例男性,平均年龄43.8岁)。入院后收集基线资料(血常规、血生化、心电图、胸片、经胸超声心动图)；行6分钟步行距离(6 Minute Walk Distance,6MWD)测试及Borg呼吸困难评分；右心导管检查测定肺动脉收缩压(PASP)、肺动脉平均压(mPAP)及舒张压、右房压(RAP)、右室压(RVP)及舒张末压,并分段取血测血氧饱和度(上腔静脉、下腔静脉、肺动脉、右心房、右心室、股动脉)以计算心排出量(CO)、心脏指数(Cl)、全肺阻力(TPR)；行左心导管测定左室舒末压。分段取血测定BNP浓度(股静脉、右心房、右心室、左心室、股动脉)。后雾化吸入伊洛前列环素20μg,吸药时间15分钟,30分钟后再次测定以上血流动力学参数并再次取各部位血液测定BNP浓度。比较吸药前后血流动力学及BNP分泌的变化。BNP检测方法：使用博适-Triage干式快速定量心肌梗死/心力衰竭诊断仪(美国Biosite公司产品)。采集全血1-2ml加入EDTA抗凝试剂管,摇匀,样品保持在室温下并在4小时内进行检测。取250μl EDTA抗凝全血加入Triage检测板,将检测板放入心力衰竭诊断仪内,15min内自动打印结果。
结果：13例患者资料完整获取。1.经胸超声心动图(TTE)测量PAH患者右房、右室增大,PASP升高,BNP、UA血浆水平增加,PAH心功能分级、Borg呼吸困难评分增加。6MWD与右房平均压、右室舒末径、PAH分级明显负相关。多元回归分析发现,右室舒末径、PAH心功能分级与6MWD负相关2.雾化吸入伊洛前列环素后,右房平均压(mRAP)、右室平均压(mRVP)、肺动脉收缩压(PASP)、肺动脉平均压(mPAP)、全肺阻力(TPR)下降,均具有统计学意义。心指数(CI)、混合静脉血氧饱和度(SvO2)上升,具有统计学意义。3.PAH患者BNP分泌增加,吸药前各部位BNP血浆水平比较左心室>股动脉>右心房>右心室>股静脉,但各部位差异未达到统计学意义。吸药前股静脉BNP浓度与右房平均压(mRAP)、右室平均压(mRVP)、右室舒末压、Borg呼吸困难评分、PAH心功能分级正相关,与6MWD呈负相关。多元回归分析发现,右房收缩压、右室平均压、PAH心功能分级与股静脉血浆BNP的水平相关。吸药前股动脉与右房平均压、右室平均压、右室舒末压、PASP、mPAP、Borg呼吸困难评分、PAH心功能分级正相关,与6MWD呈负相关。多元回归分析发现,右房收缩压与股动脉血浆BNP的水平相关。4.吸药后,各部位BNP血浆水平均下降,具体比较左心室>右心室>股动脉>右心房>股静脉,但各部位差异未达到统计学意义。右心房(P<0.05)、左心室(P<0.01)、股静脉(P<0.05)血浆BNP下降明显,差异有统计学意义。股动脉、右心室也有下降趋势,但未达统计学意义。吸药前,右房BNP分泌大于右室,而吸药后右室大于右房。
结论：1.6MWD、Borg呼吸困难评分、BNP血浆水平、UA、TTE指标及PAH心功能分级是评估PAH患者病情严重程度的有效指标。右心导管测得的右房压是诊断和评估PAH患者病情的重要指标,右心导管检查具有重要指导作用。2.吸入伊洛前列环素后,右房压、右室压、PASP、mPAP、TPR下降,CI、SvO2上升。表明吸入伊洛前列环素对PAH患者血流动力学有重要影响。3.PAH患者血浆BNP水平增加,各部位中以左室水平最高,提示可能存在左室心肌细胞分泌BNP直接入心腔的可能。在PAH患者中左室舒张功能也有一定程度受损,需进一步研究。4.吸入伊洛前列环素后对血浆BNP水平有影响,吸药后各部位BNP水平下降,且左心室、右心房、股静脉血浆水平下降明显。
Background:Pulmonary arterial hypertension (PAH) was a progressive disease characterized by progressive pulmonary vascular resistance increased, eventually leading to right heart failure and death. Right heart failure is a common pathway of death and disability in patients with all types of PAH, and PAH is also the main reason for right heart failure. Brain natriuretic peptide (BNP) is mainly secreted from the cardiac ventricular in response to ventricular volume expandion and pressure overload quickly. Studies showed that BNP would be an index for diagnose heart dysfunction with higher sensitivity and specificity than other natriuretic peptides. As an analogue of prostacyclin, nebulized iloprost have the favorable effect of selective vasodilation and may be a prospective agent to control the PAH.
Objective:The study is to explore the BNP secretion in different position (femoral vein, right atrium, right ventricle, left ventricle, femoral artery) of PAH patients, and the effect of hemodynamic parameters and the BNP plasma levels on acute pulmonary vasodilator test after iloprost inhalation.
Method:Randomly selected 13 cases from the patients hospitalized in our hospital from 2008 to 2010, all of them were diagnosed of pulmonary hypertension through Color Doppler. In these patients, there were 10 females and 3 males, mean age 43.8. After being admitted to hospital, we collected the baseline data (blood, blood biochemistry, electrocardiogram, chest X-ray, Transthoracic echocardiography); 6 minutes walk distance (6MWD) and Borg dyspnea rating (Borg scale); Determination of pulmonary artery systolic pressure (PASP), mean pulmonary artery pressure (mPAP), diastolic pulmonary artery pressure, right atrium pressure, right ventricular pressure and right ventricular end-diastolic pressure with right catheterization; Subsection blood oxygen saturation were measured (superior vena cava, inferior vena cava, pulmonary artery, right atrium, right ventricle) for calculation the pulmonary vascular resistance, cardiac output, cardiac index, total pulmonary resistance. With left catheterization, left ventricular end-diastolic pressure was detemined. Blood sample were measured for plasma BNP levels in different position (femoral vein, right atrium, right ventricle, left ventricle, femoral artery). All patients inhaled iloprost via nebulized aerosol at a dose of 20μg for 15min continuously, then the hemodynamic parameters and the plasma BNP levels were determined again. Measurement of BNP plasma levels:All samples were collected by puncture into ethylene diamine tetra acetic acid (EDTA) tubes. The blood samples were kept at room temperature and analyzed within 4h,250μl of the whole blood was added to the Triage BNP. Then the device was placed into the Triage Meter, which measures the fluorescence intensity of the BNP assay zone. The assay was completed in approximately 15min.
Results:13 patients have complete data acquisition.1. Both of the right atrium and ventricular were enlarged with Transthoracic echocardiography in PAH patients, PASP, BNP, Uric acid (UA), PAH heart functions class, Borg scale were increased. There were negative correlation between the 6MWD and mean right atrium pressure (r=-0.594, P<0.05), right ventricular end-diastolic diameter (r=-0.692, P<0.05), and PAH heart functions class (r=-0.843, P<0.01). Multiple regression analysis showed that right ventricular end-diastolic diameter, PAH heart functions class were independent determinants of 6MWD.2. After iloprost inhalation, the right atrium mean pressure, right ventricle mean pressure, PASP, mPAP, total pulmonary resistance were all significantly declined. Cardiac index, mixed venous oxygen saturation were both increased.3. The plasma BNP levels was in the patient with PAH before inhaling drug, the secretion level for plasma BNP were left ventricle> femoral artery> right atrium> right ventricle> femoral vein, but there were no statistical significance. Plasma BNP levels were significantly related with mean right atrium pressure, mean right ventricle pressure, right ventricle diastolic pressure, 6MWD, Borg scale, PAH heart functions class. Multiple regression analysis showed that there were positive correlation between the plasma BNP levels and RA systolic pressure or and RV mean pressure or and PAH heart functions class respectively.4. After iloprost inhalation, BNP secretion declined significantly in right atrium (P<0.05), femoral vein (P<0.05), left ventricle (P<0.05). Right ventricle and femoral artery had been a downward trend, but had no statistical significance. The BNP secretion of right atrium was more than right ventricle before inhalation, but after inhalation the latter more than the former.
Conclusions:1.6MWD, Borg scale, plasma BNP levels, PAH heart functions class, UA and join TTE were effective index to evaluate PAH patients'condition.2. Iloprost inhalation had important influence to PAH patients hemodynamic. After iloprost inhalation, right atrium pressure, right ventricular pressure, PASP, mPAP, total pulmonary resistance were decreased and cardiac index, mixed venous oxygen saturation were increased.3. BNP secreted was increased in PAH patients, and each part of the highest was left ventricular. This situation show that left ventricular also had certain degree of damage in PAH patients.4. Iloprost had influenced to plasma BNP levels. After iloprost inhalation, each part of plasma BNP levels had decreased and left ventricular, right atrium, femoral veins dropped significantly.
引文
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