Effects of inhaled iloprost on right ventricular contractility,right ventriculo-vascular coupling and ventricular interdependence: a randomized placebo-controlled trial in an experimental model of acute pulmonary hypertension

Introduction  

Prostacyclin inhalation is increasingly used to treat acute pulmonary hypertension and right ventricular failure, although its pharmacodynamic properties remain controversial. Prostacyclins not only affect vasomotor tone but may also have cAMP-mediated positive inotropic effects and modulate autonomic nervous system tone. We studied the role of these different mechanisms in the overall haemodynamic effects produced by iloprost inhalation in an experimental model of acute pulmonary hypertension.     

Effects of levosimendan on acute pulmonary embolism-induced right ventricular failure

OBJECTIVE: Repeated episodes of pulmonary embolism can persistently increase pulmonary arterial pressure and depress right ventricular contractility. We investigated the effects of levosimendan on right ventricular-pulmonary arterial coupling in this model of right ventricular failure. DESIGN: Prospective, controlled, randomized animal study. SETTING: University research laboratory. SUBJECTS: Fourteen anesthetized piglets. INTERVENTIONS: Repeated acute pulmonary embolisms were induced with autologous blood clots to induce persistent right ventricular failure. Animals were randomly assigned to a control or levosimendan group. Levosimendan 20 microg/kg was administered in 10 mins followed by 0.2 microg/kg/min or same volumes of isotonic saline. MEASUREMENTS AND MAIN RESULTS: Pulmonary artery distal resistance and proximal elastance by pressure-flow relationships and vascular impedance were measured. We noted right ventricle contractility by the end-systolic pressure-volume relationship (Ees), pulmonary artery effective elastance by the end-diastolic to end-systolic relationship (Ea), and right ventricular-pulmonary arterial coupling efficiency by the Ees/Ea ratio. The gradual pulmonary artery embolism increased pulmonary artery resistance and elastance, increased Ea from 1.01 +/- 0.17 to 5.58 +/- 0.37 mm Hg/mL, decreased Ees from 1.75 +/- 0.12 to 1.29 +/- 0.20 mm Hg/mL, and decreased Ees/Ea from 1.74 +/- 0.20 to 0.24 +/- 0.09. Compared with placebo, levosimendan decreased pulmonary arterial elastance and characteristic impedance. Right ventricular-pulmonary arterial coupling was restored by both an increase in right ventricular contractility and a decrease in right ventricular afterload. CONCLUSIONS: A gradual increase in pulmonary artery pressure induced by pulmonary embolism persistently worsens pulmonary artery hemodynamics, right ventricular contractility, right ventricular-pulmonary arterial coupling, and cardiac output. Levosimendan restores right ventricular-pulmonary arterial coupling better than placebo, because of combined pulmonary vasodilation and increased right ventricular contractility.     

Right atrial and ventricular strain detects subclinical changes in right ventricular function in precapillary pulmonary hypertension

The International Journal of Cardiovascular Imaging - Right ventricular (RV) ejection fraction (EF) by cardiac magnetic resonance (CMR) correlates to outcome in precapillary pulmonary hypertension...     

Prostacyclin and right ventricular function in patients with pulmonary hypertension associated with ARDS

Eight patients who developed pulmonary artery hypertension during the adult respiratory distress syndrome (ARDS) were treated with an infusion of prostacyclin (PGI₂, 12.5–35.0 ng·kg^–1·min^–1) for 45 min. We examined whether reducing the right ventricular (RV) outflow pressures by PGI₂ infusion would increase the right ventricular ejection fraction (RVEF) measured by thermodilution. PGI₂ reduced the pulmonary artery pressure (PAP) from 35.6 to 29.1 mmHg (p<0.01). The cardiac index (CI) increased from 4.2 to 5.81·min^–1·m^–2 (p<0.01) partly due to an increased stroke volume. The decreased PAP together with the increased CI resulted in a fall of the calculated pulmonary vascular resistance index (PVRI, from 5.1 to 2.5 mmHg·min·m²·1^–1,p<0.01). In the patients with subnormal baseline RVEF the increased stroke volume was associated with an increased RVEF (from 47.6% to 51.8%,p<0.05) suggesting improved RV function. This result was underscored by a significant relationship between the changes in PVRI and RVEF (r=0.789, % RVEF=–2.11·PVRI-1.45). Despite an increased venous admixture from 27.8% to 36.9% (p<0.05) the arterial PO₂ remained constant resulting in an increased oxygen delivery from 657 to 894 ml·min^–1·m^–2 (p<0.01). We conclude that short term infusions of PGI₂ increased CI concomitant to improved RV function parameters when baseline RVEF was depressed. Since improved oxygen availability should be a major goal in the management of patients with ARDS PGI₂ may be useful to lower pulmonary artery pressure in ARDS.Supported by the Deutsche Forschungsgemeinschaft (grant Fa 139/2-2)     

肺血栓栓塞患者右心功能的临床研究

目的 利用彩色多普勒超声心动图观察肺血栓栓塞患者的右心功能. 方法 应用超声心动图观察31例肺血栓栓塞患者(研究组)右心室壁运动及右心室收缩整体功能,并计算其右心功能指数,以3l例同年龄组心血管疾病及其危险因素相似的志愿者为对照. 结果 肺血栓栓塞患者右房室内径及右心室舒张末期容积、主肺及右肺动脉内径均大于对照组(P<0.01);右心室前壁运动幅度、右心室射血分数低于对照组(P<0.01).三尖瓣前向血流频谱显示,研究组早期充盈E峰减低,E/A比与对照组相比下降(P<0.01);研究组等容舒张期和等容收缩期延长,右心室射血期缩短,右心室心肌工作指数增大(P<0.01),右心室心肌工作指数与右心室射血分数(r=0.78,P<0.01)、等容舒张期和等容收缩期有高度相关性(r分别为0.88、0.57,均P<0.01). 结论 肺血栓栓塞患者右心舒缩功能下降,右心室心肌工作指数可较敏感反映这一变化.     

Efficiency of prostacyclin in the treatment of protamine-mediated right ventricular failure and acute pulmonary hypertension

Protamine is used after cardiopulmonary bypass was stopped in order to reverse the anticoagulant effects of heparin administered during open-heart operations. Adverse hemodynamic responses to protamine are common, ranging from minor perturbations to cardiovascular collapse. The aim of the present study was to investigate whether a prostacyclin is effective in the treatment of protamine-mediated acute pulmonary hypertension and right ventricular failure in the perioperative period of isolated coronary artery bypass grafting (CABG) operations. In sixty-eight (1.78%) of 3800 patients who underwent isolated CABG, acute pulmonary hypertension and right ventricular failure developed during or following the protamine infusion. These 68 patients were included in the study and were randomized into two groups. Thirty-eight of the patients received prostaglandin I(2) (PGI(2)), norepinephrine and dopamine (PGI(2) group), whereas 30 patients received nitroglycerin, norepinephrine and dopamine (control group). Hemodynamic data were recorded before and after the above drug combinations. The mean value of left ventricle ejection fraction significantly increased (p < 0.05) and mean values of central venous pressure, pulmonary artery systolic and diastolic pressure, pulmonary capillary wedge pressure and pulmonary vascular resistance significantly decreased (p < 0.05) in the PGI(2) group. The mean value of pulmonary capillary wedge pressure significantly decreased (p < 0.05) and the mean value of central venous pressure significantly increased (p < 0.05) in the control group. In conclusion, prostacyclin (PGI(2)) is effective in the treatment of protamine-mediated acute pulmonary hypertension and right ventricular failure in the perioperative period in isolated CABG operations. This finding may be an important contribution to the treatment of severe protamine complications during open-heart operations.     

Impact of right ventricular dyssynchrony on left ventricular performance in patients with pulmonary hypertension

Pulmonary hypertension has been associated with right ventricular (RV) dyssynchrony which may induce left ventricular (LV) dysfunction and dyssynchrony through ventricular interdependence. The present study evaluated the influence of RV dyssynchrony on LV performance in patients with pulmonary hypertension. One hundred and seven patients with pulmonary hypertension (age 63 ± 14 years, systolic pulmonary arterial pressure 60 ± 19 mmHg) and LV ejection fraction (EF) >35 % were evaluated. Ventricular dyssynchrony was assessed with speckle tracking echocardiography and defined as the standard deviation of the time to peak longitudinal strain of six segments of the RV (RV-SD) and the LV (LV-SD) in the apical 4-chamber view. Mean RV-SD and LV-SD assessed with longitudinal strain speckle tracking echocardiography were 51 ± 28 and 47 ± 21 ms, respectively. The patient population was divided according to the median RV-SD value of 49 ms. Patients with RV-SD ≥49 ms had significantly worse NYHA functional class (2.7 ± 0.7 vs. 2.3 ± 0.7, p = 0.004), RV function (tricuspid annular plane systolic excursion: 16 ± 4 vs. 19 ± 4 mm, p < 0.001), LVEF (50 ± 10 vs. 55 ± 8 %, p = 0.001), and larger LV-SD (57 ± 18 vs. 36 ± 18 ms, p < 0.001). RV-SD significantly correlated with LV-SD (r = 0.55, p < 0.001) and LVEF (r = ?0.23, p = 0.02). Multiple linear regression analysis showed an independent association between RV-SD and LV-SD (β = 0.35, 95 %CI 0.21–0.49, p < 0.001). RV dyssynchrony is significantly associated with LV dyssynchrony and reduced LVEF in patients with pulmonary hypertension.     

多普勒组织成像评价房间隔缺损并肺动脉高压患者右心室收缩功能

目的探讨多普勒组织成像(DTI)技术评价房间隔缺损(ASD)并肺动脉高压患者右心室收缩功能的临床意义.方法 56例ASD并肺动脉高压患者按肺动脉高压程度分为轻、中、重3组,并选取22例健康人作为正常对照组,采用DTI技术取四腔心切面检测所有受检者三尖瓣前叶瓣环收缩期峰值速度(S波)及收缩期峰值加速时间(AC),并进行组间比较.结果 ASD并轻、中度肺动脉高压组S波均高于正常组(P＜0.05或P＜0.01),而重度组S波则低于正常组(P＜0.05).ASD并轻、中及重度肺动脉高压组AC均长于正常组(P＜0.05),且3组间相比也有显著性差异(P＜0.05),并随肺动脉压力增加,明显延长.结论 DTI技术可用于评价ASD并肺动脉高压患者的右心室收缩功能,是一种无创、简便、定量评价右心室收缩功能的新技术.     

Altered synchrony of right ventricular contraction in borderline pulmonary hypertension

Imaging studies have shown that pulmonary hypertension (PH) is associated with inhomogenous right ventricular (RV) regional contraction, or dyssynchrony, and that this is of prognostic relevance. This study aimed at the identification and functional significance of RV dyssynchrony in borderline PH defined by a mean pulmonary artery pressure between (mPAP) 20 and 25 mmHg. RV dyssynchrony was measured by 2-dimensional speckle tracking echocardiography in 17 patients with pulmonary arterial hypertension (PAH), 13 patients with borderline PH and 14 controls. Dyssynchrony was defined as the R-R interval-corrected standard deviation of the times to peak-systolic strain for the basal and medium segments of the RV. All the PH patients underwent a right heart catheterization. RV dyssynchrony amounted to 69?±?34 ms in PAH, 47?±?23 ms in borderline PH and 8?±?6 ms in controls, all different from each other (p?<?0.05). RV dyssynchrony in borderline PH was the only parameter of RV systolic dysfunction in 11 of 13 (85%) of the patients. RV dyssynchrony was accompanied by postsystolic shortening and correlated to RV fractional area change, not to mPAP or pulmonary vascular resistance. RV dyssynchrony occurs in borderline PH and may reflect early RV-arterial uncoupling.     

超声心动图对伴肺动脉高压的房间隔缺损患者右心室功能的研究

目的 探讨右心室Tei指数检查伴肺动脉高压的房间隔缺损患者右心室功能的价值.方法 伴不同程度肺动脉高压的房间隔缺损患者28例,正常对照组33例,分别采用脉冲波多普勒成像和组织多普勒成像技术测算右室Tei指数1和Tei指数2.结果 伴不同程度肺动脉高压的房间隔缺损患者右心室Tei指数1、Tei指数2均明显大于正常对照组（P＜0.01）;伴中重度肺动脉高压房间隔缺损患者的右心室Tei指数1 、Tei指数2均大于伴轻度肺动脉高压房间隔缺损的患者;正常对照组、房间隔缺损组右心室Tei指数2与Tei指数1均呈正相关（P＜0.01）.结论 伴肺动脉高压的房间隔缺损患者存在不同程度的右室功能降低;右室Tei指数能较全面准确地评价右心室功能;而由组织多普勒脉冲法获取的右心室Tei指数更简便、易行,且准确性高,是对传统血流多普勒方法的改进和有益补充.     

大鼠肠缺血再灌注损伤后肠黏膜免疫功能的变化与意义

目的 :观察大鼠肠缺血再灌注损伤后肠黏膜免疫功能的变化 ,并探讨其与肠源性细菌内毒素移位的关系。方法 :采用大鼠小肠缺血 45min再灌注模型 ,分别于再灌注后即刻、2h、6h、2 4h用免疫放射法测定肠黏膜组织中分泌型免疫球蛋白A(sIgA)的含量 ;四甲基偶氮唑盐微量酶反应比色法 (MTT)测定Peyer’s淋巴结 (PP)、上皮内淋巴细胞 (IEL)和固有层淋巴细胞 (LPL)增殖活力 ;无菌取肠系膜淋巴结行细菌培养 ,统计细菌移位率 ;取门静脉血检测内毒素。结果 :肠缺血再灌注后肠黏膜中sIgA含量及淋巴细胞增殖活性均明显下降 (P <0 0 1) ,血浆内毒素含量较再灌注前显著升高 (P <0 0 1) ;并于再灌注后 2h起出现肠系膜淋巴结细菌移位 ;肠黏膜内sIgA含量及肠道相关淋巴组织淋巴细胞增殖活力与肠源性细菌内毒素移位呈显著负相关 (r =-0 5 5 3～ -0 75 3 ,P <0 0 1)。结论 :肠缺血再灌注损伤后肠黏膜免疫功能下降 ,与肠外细菌内毒素移位的发生密切相关。     

ET-1与肺动脉高压右室功能相关关系的研究

目的:探讨内皮素-1(ET-1)在肺动脉高压(PH)右室功能损害、右室重塑病理生理过程中的作用和相关关系.方法:PH组58例,非PH组23例,对照组20例.超声心动图分别测量三尖瓣前向血流及反流频谱、肺动脉前向血流频谱;ET-1的测定采用非平衡法.结果:PH组与非PH组及正常对照组相比,E、E/A显著降低,A增加,PV显著降低,IRT、ICT显著延长,Tei指数显著增加(P<0.001);血浆ET-1浓度显著增高,与肺动脉收缩压正相关.ET-1与E/A、PV负相关,与A、IRT、ICT正相关.结论:ET-1参与了肺动脉高压及右室功能减退的病理生理过程.     

Effects of inhaled nitric oxide on right ventricular function in severe acute respiratory distress syndrome

Objective To compare the effects of inhaled nitric oxide (NO) and an infusion of prostacyclin (PGI₂) on right ventricular function in patients with severe acute respiratory distress syndrome (ARDS).Design Randomized prospective short-term study.Setting: Post-surgical ICU in an university hospital.Patients 10 patients with severe ARDS referred to our hospital for intensive care.Interventions In random sequence the patients inhaled NO at a concentration of 18 parts per million (ppm) followed by 36 ppm, and received an intravenous infusion of PGI₂ (4 ng·kg^–1·min^–1).Measurement and results Inhalation of 18 ppm NO reduced the means (±SE) pulmonary artery pressure (PAP) from 33±2 to 28±1 mmHg (p=0.008), increased right ventricular ejection fraction (RVEF), as assessed by thermodilution technique, from 28±2 to 32±2% (p=0.005), decreased right ventricular end-diastolic volume index from 114±6 to 103±8 ml·m^–2 (p=0.005) and right ventricular end-systolic volume index from 82±4 to 70±5 ml·m^–2 (p=0.009). Mean arterial pressure (MAP) and cardiac index (CI) did not change significantly. The effects of 36 ppm NO were not different from the effects of 18 ppm NO. Infusion of PGI₂ reduced PAP from 34±2 to 30±2 mmHg (p=0.02), increased RVEF from 29±2 to 32±2% (p=0.02). Right ventricular end-diastolic and end-systolic volume indices did not change significantly. MAP decreased from 80±4 to 70±5 mmHg (p=0.03), and CI increased from 4.0±0.5 to 4.5±0.5 l·min^–1·m^–2 (p=0.02).Conclusions Using a new approach to selective pulmonary vasodilation by inhalation of NO, we demonstrate in this groups of ARDS patients that an increase in RVEF is not necessarily associated with a rise in CI. The increase in CI during PGI₂ infusion is probably related to the systemic effect of this substance.Supported by DFG Fa 139/1-2/2-2     

肺动脉-左心房无泵肺辅助对急性肺损伤动物模型右心室负荷影响

目的:探讨肺动脉一左心房无泵肺辅助对幼猪急性肺损伤动物模型右心室负荷的影响,明确该辅助策略的可行性.方法:12只健康实验用中华小型猪以油酸诱导急性肺损伤模型后,随机分为2组:对照组6只,急性肺损伤模型建立后,仅给予常规机械通气;肺辅助组6只,常规机械通气,肺动脉-左心房无泵肺辅助.监测2组中心静脉压、肺动脉压、心输出量和辅助循环流量.结果:对照组肺动脉压呈持续性升高,至E时点肺动脉压升高至(40.9±9.0)mm Hg.明显高于B时点(P=0.005).肺辅助组于B时点开始肺辅助后,可见到血液流经辅助装置;肺动脉压呈下降趋势.至E时点降至(25.3±1.9)mm Hg,明显低于B时点(P=0.047);对照组和肺辅助组D时点和E时点肺动脉压差异有统计学意义(P=0.002).结论:肺动脉一左心房无泵肺辅助不增加急性肺损伤时右心室额外负荷,且有利于卸载右心室后负荷.     

Effects of age and pulmonary arterial hypertension on the different phases of right atrial function

To evaluate the effects of age and pulmonary hypertension on phasic right atrial function we measured right atrial volumes at 3 different points in the cardiac cycle in 57 healthy subjects and 33 patients with pulmonary arterial hypertension. Right atrial reservoir function was assessed by systolic filling volume and passive and active emptying by passive and active emptying volume and fraction of total emptying. We compared these phases of right atrial function in 30 healthy subjects <60 and 27 >/= 60 years old, and in a separate analysis, in 33 patients with pulmonary arterial hypertension and 33 matched controls. Healthy subjects >/=60 years had lower passive emptying fraction (46.0 +/- 23.3% vs 59.9 +/- 15.4%, P = 0.011) and larger active emptying volume (7.0 +/- 3.5 vs 4.9 +/- 2.5 ml/m(2), P = 0.013 ) and fraction (54.0 +/- 23.3% vs 40.1 +/- 15.4%, P = 0.011) compared to those <60. Patients with pulmonary arterial hypertension had larger right atrial volumes, systolic filling volume (18.3 +/- 6.9 vs 12.3 +/- 4.9 ml/m(2), P 相似文献   

利伐沙班对急性非高危肺血栓栓塞症患者细胞因子及右心功能的影响

目的 探讨利伐沙班对急性非高危肺血栓栓塞症患者细胞因子及右心功能的影响.方法 选取确诊急性非高危肺血栓栓塞症患者104例,随机分为对照组(n=52)和观察组(n=52),对照组给予常规治疗,观察组在对照组基础上采用利伐沙班治疗.比较2组总有效率、细胞因子指标[D-二聚体(D-D)、C反应蛋白(CRP)、白细胞介素-10...     

B-type natriuretic peptide as an indicator of right ventricular dysfunction in acute pulmonary embolism

Objective: B‐type natriuretic peptide (BNP) is a neurohormone secreted from cardiac ventricles in response to ventricular strain. The aim of present study was to evaluate the role of BNP in the diagnosis of the right ventricular (RV) dysfunction in acute pulmonary embolism (PE). Methods: BNP levels were measured in patients with acute PE as diagnosed by high probability lung scan or positive spiral computed tomography. All patients underwent standard echocardiography and blood tests during the second hour of the diagnosis. Results: Forty patients diagnosed as acute PE (mean age, 60.4 ± 13.2 years; 62.5% women) were enrolled in this study. Patients with RV dysfunction had significantly higher BNP levels than patients without RV dysfunction (426 ± 299.42 pg/ml vs. 39.09 ± 25.22 pg/ml, p < 0.001). BNP‐discriminated patients with or without RV dysfunction (area under the receiver operating characteristic curve, 0.943; 95% CI, 0.863–1.022). BNP > 90 pg/ml was associated with a risk ratio of 165 (95% CI, 13.7–1987.2) for the diagnosis of RV dysfunction. There was a significant correlation between RV end‐diastolic diameter and BNP (r = 0.89, p < 0.001). Sixteen patients (40%) were diagnosed as having low‐risk PE, 19 patients (47.5%) with submassive PE and five patients (12.5%) with massive PE. The mean BNP was 39.09 ± 25.2, 378.4 ± 288.4 and 609.2 ± 279.2 pg/ml in each group respectively. Conclusion: Measurement of BNP levels may be a useful approach in diagnosis of RV dysfunction in patients with acute PE. The possibility of RV dysfunction in patients with plasma BNP levels > 90 pg/ml should be strongly considered.     

Assessment of right ventricular function by right ventricular systolic time intervals in acute respiratory failure

OBJECTIVE: Whether right ventricular systolic time intervals accurately reflect right ventricular function in patients with acute respiratory failure was determined by assessing the correlation between right ventricular systolic time intervals and the right ventricular end-systolic pressure-volume relationship. DESIGN: A prospective study. SETTING: A surgical intensive care unit in a university hospital. PATIENTS: Twenty patients with acute respiratory failure. MEASUREMENTS AND MAIN RESULTS: Right ventricular systolic time intervals were determined by the simultaneous graphic display of the electrocardiogram, the phonocardiogram, and the pulmonary artery pressure curve and were expressed as a ratio of the pre-ejection period/right ventricular ejection time. The total electromechanical systole was measured from the onset of the electrocardiographic wave complex to the pulmonic component of the second heart sound. Right ventricular ejection time was measured from the rapid upstroke of the pulmonary artery pressure curve to the dicrotic notch. Right ventricular ejection fraction, from which right ventricular end-systolic volume was derived, was measured by the thermodilution technique. Pulmonary artery dicrotic notch pressure was used as an estimate of right ventricular end-systolic pressure. Data were collected at the baseline and after one or two alterations in preload, to define the right ventricular end-systolic pressure-volume relationship line. There was an inverse correlation between the pre-ejection period/right ventricular ejection time ratio and the slope of the right ventricular end-systolic pressure-volume relationship line (r2 = .67; p < .0001). When patients were divided into two groups, based on the pre-ejection period/right ventricular ejection time ratio, the slope of the right ventricular end-systolic pressure-volume relationship line was lower in the group with a high pre-ejection period/right ventricular ejection time ratio (p < .0001). No difference in other hemodynamic data, between the two groups, was noted. CONCLUSIONS: These data suggest that right ventricular systolic time intervals reflect right ventricular performance accurately in patients with acute respiratory failure.