Pulmonary Arterial Circulation Research Articles

Pulmonary Artery Sling: A Rare Presentation With Tracheobronchial Malacia in an Adult

INTRODUCTION: Pulmonary artery sling is a congenital vascular anomaly in which the pulmonary arterial circulation to the lung arises from the pulmonary artery (PA) of the contralateral lung rather than a mainstem PA. Tracheal compression occurs as the anomalous pulmonary artery traverses the mediastinum posterior to the airway. This anomaly, while often seen in children, rarely remains undiagnosed into adulthood. We describe a case of PA sling presenting with respiratory symptoms in an adult.

Congenital heart disease with decreased pulmonary blood flow and pulmonary arterial collateral circulation:experience with 12 patients

目的 探讨肺血减少型先天性心脏病合并体肺动脉侧支循环患儿的救治措施.方法 对2003年1月至2008年10月我院收治的12例肺血减少型先天性心脏病合并体肺动脉侧支循环患儿的临床资料进行回顾性分析.结果 本组死亡4例,病死率33.3%.外科手术前行侧支血管的栓堵或结扎术6例,死亡1例,死因为术后充血性心力衰竭.术后并发广泛肺渗出、低心排出量综合征各1例,其余3例痊愈.外科手术后行侧支血管的栓堵或结扎术5例,死亡3例,死因分别为顽固性低氧血症1例,低心排出量综合征2例.术后并发灌注肺3例,反复气道大量出血1例.侧支未作栓堵或结扎1例,经对症处理而痊愈.结论 术前明确诊断、术中选择恰当的治疗方式、术后积极防治并发症是患儿顺利恢复的关键。

Role of 64-MDCT in Evaluation of Pulmonary Atresia With Ventricular Septal Defect

The purposes of this article are to describe the technical factors in performing 64-MDCT of pulmonary atresia with ventricular septal defect (PA-VSD), to describe the anatomic variations in pulmonary arterial circulation and other associated anomalies, and to describe the postoperative evaluation of this condition. The management of this complex condition has been largely determined by the morphology of pulmonary arteries and the extracardiac sources of pulmonary blood supply. Although echocardiography and catheter angiography are the traditional imaging techniques used to diagnose PA-VSD, 64-MDCT has become a valuable noninvasive imaging technique in comprehensive evaluation of this condition.

Regional lactate and oxygen saturation gradients: preliminary experimental data

Regional differences among blood flow and oxygen uptake are widely cited but not well explained. The lactate shuttle concept, alternative sets of lactate production, nowadays, challenges our comprehension about oxygen delivery and consumption. Recent studies have shown the prognostic value of oxygen and lactate gradients measured from central venous to pulmonary artery circulation. Our data represent one sample of our 4-year experimental research, trying to build a conceptual framework related to oxygen and lactate dynamic in different hypoxic states.

FRAGMATIC: A randomised phase III clinical trial investigating the effect of fragmin® added to standard therapy in patients with lung cancer

BackgroundVenous thromboembolism (VTE) occurs when blood clots in the leg, pelvic or other deep vein (deep vein thrombosis) with or without transport of the thrombus into the pulmonary arterial circulation (pulmonary embolus). VTE is common in patients with cancer and is increased by surgery, chemotherapy, radiotherapy and disease progression. Low molecular weight heparin (LMWH) is routinely used to treat VTE and some evidence suggests that LMWH may also have an anticancer effect, by reduction in the incidence of metastases. The FRAGMATIC trial will assess the effect of adding dalteparin (FRAGMIN), a type of LMWH, to standard treatment for patients with lung cancer.Methods/DesignThe study design is a randomised multicentre phase III trial comparing standard treatment and standard treatment plus daily LMWH for 24 weeks in patients with lung cancer. Patients eligible for this study must have histopathological or cytological diagnosis of primary bronchial carcinoma (small cell or non-small cell) within 6 weeks of randomisation, be 18 or older, and must be willing and able to self-administer 5000 IU dalteparin by daily subcutaneous injection or have it administered to themselves or by a carer for 24 weeks. A total of 2200 patients will be recruited from all over the UK over a 3 year period and followed up for a minimum of 1 year after randomisation. Patients will be randomised to one of the two treatment groups in a 1:1 ratio, standard treatment or standard treatment plus dalteparin. The primary outcome measure of the trial is overall survival. The secondary outcome measures include venous thrombotic event (VTE) free survival, serious adverse events (SAEs), metastasis-free survival, toxicity, quality of life (QoL), levels of breathlessness, anxiety and depression, cost effectiveness and cost utility.Trial registrationCurrent Controlled Trials ISRCTN80812769

Quality Improvement Guidelines for the Treatment of Lower Extremity Deep Vein Thrombosis with Use of Endovascular Thrombus Removal

Suresh Vedantham, MD, Akhilesh K. Sista, MD, Seth J. Klein, MD, Lina Nayak, MD, Mahmood K. Razavi, MD, Sanjeeva P. Kalva, MD, Wael E. Saad, MD, Sean R. Dariushnia, MD, Drew M. Caplin, MD, Christine P. Chao, MD, Suvranu Ganguli, MD, T. Gregory Walker, MD, and Boris Nikolic, MD, MBA, for the Society of Interventional Radiology and Cardiovascular and Interventional Radiological Society of Europe Standards of Practice Committees

Rho‐kinase inhibition abolishes the vasoconstrictor response to hypoxia in the infant piglet pulmonary arterial circulation

We examined the effects of the rho‐kinase inhibitor fasudil on the regional response of the infant pulmonary arterial (PA) circulation to hypoxia. 15 two week old piglets were instrumented to record PA pressure (PAP). Control animals (n=7) were exposed to hypoxia (FiO2 = 0.05). Treated animals (n=8) were infused with fasudil (5mg/Kg) before and during hypoxia. Input mean impedance (Zm, reflecting distal arteriolar vasoconstriction) and characteristic impedance (Zo, reflecting proximal arteriolar opposition to flow) were calculated.Hypoxia caused a potent vasoconstrictor response distally (increased Zm). Zo was unchanged indicating no alteration of the proximal circulation. Pre‐treatment with fasudil completely abolished the increase in Zm and PAP indicating that the distal vasoconstrictor response is rho‐kinase dependent. Rho‐kinase inhibitors may be an effective therapy for hypoxic pulmonary hypertension in infants, but may be limited by its effect on systemic blood pressure. Funded by Dept. of Surgery, Mass. Gen. Hosp.

Not Just Big Kids

Atrial septal defects (ASDs), allowing blood to directly communicate between systemic and pulmonary arterial circulations at the atrial level, are among the most common congenital cardiac anomalies seen in the adult population. The degree of shunting across an ASD is directly related to the area of the ASD and inversely related to the compliance of the combined atrial-ventricular chambers on either side of the heart. Under normal physiological conditions, there is net left-to-right shunting across an ASD, as the left ventricle is far less compliant than the right ventricle. This shunt of fully oxygenated blood back to the right atrium results in a volume load to the right-sided heart chambers and to the pulmonary vasculature; if left untreated, large-volume left-to-right shunting can result in atrial arrhythmias, right ventricular diastolic and systolic failure, worsened functional class, decreased exercise capacity, left ventricular diastolic failure, and, uncommonly, development of pulmonary arterial hypertension.1 The indication to treat an ASD is typically related to its hemodynamic significance and its effects on the right ventricle. National care guidelines denote ASD closure with class IA recommendation in patients with evidence …

Clinical and epidemiological features of a series of 73 cases of pulmonary embolism admitted to an ICU

Pulmonary embolism (PE) is a clinical syndrome resulting from occlusion of the pulmonary arterial circulation from one or more emboli. In the United States, its incidence is estimated at 1/1,000 hospital admissions per year [1].

Individualized approach to the surgical treatment of tetralogy of Fallot with pulmonary atresia

Tetralogy of Fallot with pulmonary atresia is a heterogeneous group of defects, characterised by diverse sources of flow of blood to the lungs, which often include multiple systemic-to-pulmonary collateral arteries. Controversy surrounds the optimal method to achieve a biventricular repair with the fewest operations while basing flow to the lungs on the native intrapericardial pulmonary arterial circulation whenever possible. We describe an individualized approach to this group of patients that optimizes these variables. Over a consecutive 10-year period, we treated 66 patients presenting with tetralogy of Fallot and pulmonary atresia according to the source of the pulmonary arterial flow. Patients were grouped according to whether the flow of blood to the lungs was derived exclusively from the intrapericardial pulmonary arteries, as seen in 29 patients, exclusively from systemic-to-pulmonary collateral arteries, as in 5 patients, or from both the intrapericardial pulmonary and collateral arteries, as in the remaining 32 patients. We divided the latter group into 9 patients deemed simple, and 23 considered complex, according to whether the pulmonary arterial index was greater than or less than 90 millimetres squared per metre squared, and whether the number of collateral arteries was less than or greater than 2, respectively. We achieved complete biventricular repair in 58 patients (88%), with an overall mortality of 3%. Repair was accomplished in a single stage in all patients without systemic-to-pulmonary collateral arteries, but was staged, with unifocalization, in the patients lacking intrapericardial pulmonary arteries. Complete repair without unifocalization was achieved in all patients with the simple variant of the mixed morphology, and in 56% of patients with the complex variant. The average number of procedures per patient to achieve complete repair was 1, 2.2, 3.8, and 2.6 in patients with exclusively native intrapericardial, simple and mixed, complex and mixed and exclusively collateral pulmonary arterial flow, respectively. An individualized approach based on the morphology of the pulmonary arterial supply permits achievement of a high rate of complete intracardiac repairs, basing pulmonary arterial flow on the intrapericardial pulmonary arteries in the great majority of cases, and has a low rate of reoperation and mortality.

An experiment study of lung ischemia-reperfusion injury of pulmonary surgery in rabbit model.

The blocking of pulmonary vessels, including the blocking of pulmonary artery and pulmonary circulation, is always applied in the surgical treatment of locally advanced no-small cell lung cancer. However, the blocking of pulmonary vessels will induce lung ischemia-reperfusion injury (LIRI). The aim of this study is to establish pulmonary vessels blocking model in rabbit and to investigate the LIRI in pulmonary surgery. 114 New Zealand rabbits were randomly divided into 3 groups: group I, control group; group II, block left pulmonary artery; group III, block left pulmonary artery and vein. After the time of opening chest (group I), 1 h ischemia and 1 h, 2 h, 4 h, 6 h, 24 h reperfusion, the changes of arterial oxygen partial pressure in left pulmonary vein (PaO2) and the content of MDA in left lung tissue were observed. Then the water content of left lung and pathological study was recorded. Homodynamic parameters were stable in all 3 groups. There were significant differences in PaO2, MDA and wet/dry ratio of the lung tissue between I and other two groups at the time of 1 h ischemia and 1 h, 2 h, 4 h, 6 h reperfusion (P <0.05 and P < 0.01), but there was no significant difference between group II and group III (P >0.05), and there was no significant difference among the three groups after 24 h reperfusion (P >0.05). Pathological study revealed that similar injury changes happened between group II and group III, and the obvious injury happened at the time of 4 h reperfusion. At the time of 6 h reperfusion pathological changes in both group II and group III began to recover, and completely recover after 24 h reperfusion. The lung ischemic-reperfusion injury caused by blocking pulmonary artery is similar to that caused by blocking pulmonary artery and veins. It is safe to previously block pulmonary vessels within 1 h during pulmonary surgery.

Massive Pulmonary Emboli and CT Pulmonary Angiography

Background: Massive pulmonary embolism (PE) is a devastating form of PE which usually results in acute right ventricular failure and death within 1–2 h. Objectives: To retrospectively assess pulmonary vascular, cardiac, pleural, and parenchymal findings on CT pulmonary angiography (CTPA) in patients with a diagnosis of massive PE (systolic blood pressure <90 mm Hg, syncope and/or shock). Methods: In 33 consecutive patients with proven massive PE, hemodynamic severity was assessed by the extent of right ventricular dysfunction (RVD); diameter of the main pulmonary artery; the shape of the interventricular septum; and the extent of obstruction to the pulmonary arterial circulation (CT obstruction index). Results: Central pulmonary arteries were embolized in all patients. RVD was detected in all patients (94% of them had severe RVD); the diameter of the main pulmonary artery was wider than normal in 76% of the patients; the shape of the interventricular septum was abnormal in all patients, and the CT obstruction index was higher than or equal to 50% in 85% of the patients. Wedge-shaped pleural-based consolidation was the most common parenchymal abnormality (36%). Pleural effusions were seen in 26 patients (79%). Twenty-eight patients were alive, and only the use of thrombolytic therapy was found to be statistically significant. Conclusions: In patients with acute massive PE, embolization of the central pulmonary arteries, RVD and displacement of the interventricular septum are commonly seen with CTPA. A CT obstruction index of >50% is commonly observed in massive PE. There was no association between CTPA findings and survival.

Validation of Magnetic Resonance Phase-Contrast Flow Measurements in the Main Pulmonary Artery and Aorta Using Perivascular Ultrasound in a Large Animal Model

Phase-contrast flow magnetic resonance imaging (pc-MRI) measurements are an established technique for noninvasive assessment of hemodynamics. However, in vivo validation data on the accuracy of pc-flow especially for nonphysiologic hemodynamic conditions are missing. The goal of our work was 1) to validate pc-flow with perivascular ultrasound in different hemodynamic conditions in the main pulmonary artery (MPA) and ascending aorta (AO) and 2) to investigate the relation between pc-MRI and invasive pressure measurements. Five healthy pigs with opened chest were investigated. Ultrasound measurements were performed outside the MRI unit using a detachable MR-table. Parallel to ultrasound flow measurements, invasive pressure measurements were performed. PC-MRI (1.5 T MRI) measurements were done using a FLASH 2-dimensional sequence. First the animals were examined in normotonia, followed by hypertension (infusion of Arterenol) and hypotension (infusion of Sodiumnitropussid). Flow measurements acquired in normotonia were 2.7 +/- 0.6 L/min (ultrasound) and 2.8 +/- 0.6 L/min for pc-MRI (not significantly different, P = 0.17). During hypertonia, the blood flow increased to 3.1 +/- 0.7 and 2.7 +/- 0.8 L/min, respectively (P = 0.01). During hypotension, the blood flow decreased to 1.7 +/- 0.5 and 1.7 +/- 0.5 L/min, respectively (P = 0.7). An excellent linear correlation (taking all measurements together) between the ultrasound and pc-MRI measurements was found (r = 0.89). 95% Limits of intraindividual agreement correspond to relative differences of -36 to 44%. Systolic pressure measurements in the AO were 91 mm Hg (normotonic), 111 mm Hg (hypertonic), and 64 mm Hg (hypotonic) and in the MPA 23 mm Hg (normotonic), 29 mm Hg (hypertonic), and 20 mm Hg (hypotonic). Systolic pressure measurements showed good linear correlation with pc-MRI average flow per minute and peak velocity (AO: r = 0.79, MPA: r = 0.66). MRI pc-flow measurements are a reliable tool for noninvasive assessment of blood flow. Hemodynamic parameters derived by MRI demonstrate good linear correlations with the pressure in the systemic and pulmonary arterial circulation.

Acetazolamide for Monge's Disease

Monge's disease is characterized by an excessive erythrocytosis, frequently associated with pulmonary hypertension, in high-altitude dwellers. It has a considerable impact on public health in high-altitude regions. A preliminary study demonstrated the efficiency of acetazolamide (Acz) (250 mg/d for 3 wk) in reducing serum erythropoietin and hematocrit. Evaluate the efficacy and tolerance of a 6-month treatment with 250 mg Acz that could be chronically implemented and its effects on pulmonary artery pressure and cardiac function. A two-phase study was performed in patients (hematocrit > or = 63%) from Cerro de Pasco, Peru (4,300 m). First phase: a double-blind, placebo-controlled study in 55 patients who received a single dose of either 250 mg Acz (n = 40) or placebo (n = 15) by daily oral administration for 12 weeks. Second phase (open label): after a 4-week washout period, all patients received 250 mg Acz for 12 weeks. Hematocrit, blood gases, clinical outcome, and pulmonary artery circulation were evaluated. First phase: Acz decreased by 44% the number of polycythemic subjects (P = 0.02), decreased hematocrit from 69 to 64% (P < 0.001), and increased arterial O(2) pressure from 42 to 45 mm Hg (P < 0.001). No severe adverse effect or hypokalemia was recorded. The second phase reproduced the effects observed during the first phase, without cumulative effects on hematocrit. A 4-week washout restored basal hematocrit. Only patients who received Acz for 6 months showed a clear reduction in pulmonary vascular resistance. Acz reduces erythrocytosis and improves pulmonary circulation in Monge's disease without adverse effects. Its implementation as a chronic treatment for this disease appears efficient and safe.

Magnetic resonance imaging findings of persistent primitive hepatic venous plexus with complex congenital cardiac disease

Persistence of the primitive hepatic venous plexus (PPHVP) is an uncommon anomaly that can present associated with complex congenital heart disease and inferior vena cava (IVC) development anomalies and complicate endovascular and surgical procedures. We report a case of PPHVP in a patient with complex congenital heart disease with unexplained persistent arterial desaturation after Kawashima operation and describe magnetic resonance angiography (Angio-MRI) findings leading to the diagnosis. We recommend that IVC-Angio-MRI be performed in preoperative evaluation of patients with complex congenital heart disease and left isomerism when redirection of systemic venous blood to the pulmonary arterial circulation is considered.

Shear stress paradigm for perinatal fractal arterial network remodeling in lambs with pulmonary hypertension and increased pulmonary blood flow

Congenital heart disease with increased blood flow commonly leads to the development of increased pulmonary vascular reactivity and pulmonary arterial hypertension by mechanisms that remain unclear. We hypothesized a shear stress paradigm of hemodynamic reactivity and network remodeling via the persistence and/or exacerbation of a fetal diameter bifurcation phenotype [parent diameter d(0) and daughters d(1) >or= d(2) with alpha < 2 in (d(1)/d(0))(alpha) + (d(2)/d(0))(alpha) and area ratio beta < 1 in beta = (d(1)(2)+ d(2)(2))/ d(0)(2)] that mechanically acts as a high resistance magnifier/shear stress amplifier to blood flow. Evidence of a hemodynamic influence on network remodeling was assessed with a lamb model of high-flow-induced secondary pulmonary hypertension in which an aortopulmonary graft was surgically placed in one twin in utero (Shunt twin) but not in the other (Control twin). Eight weeks after birth arterial casts were made of the left pulmonary arterial circulation. Bifurcation diameter measurements down to 0.010 mm in the Shunt and Control twins were then compared with those of an unoperated fetal cast. Network organization, cumulative resistance, and pressure/shear stress distributions were evaluated via a fractal model whose dimension D(0) approximately alpha delineates hemodynamic reactivity. Fetus and Control twin D(0) differed: fetus D(0)=1.72, a high-resistance/shear stress amplifying condition; control twin D(0) = 2.02, an area-preserving transport configuration. The Shunt twin (D(0)=1.72) maintained a fetal design but paradoxically remodeled diameter geometry to decrease cumulative resistance relative to the Control twin. Our results indicate that fetal/neonatal pulmonary hemodynamic reactivity remodels in response to shear stress, but the response to elevated blood flow and pulmonary hypertension involves the persistence and exacerbation of a fetal diameter bifurcation phenotype that facilitates endothelial dysfunction/injury.

MRI Measurement of the Hemodynamics of the Pulmonary and Systemic Arterial Circulation: Influence of Breathing Maneuvers

The purpose of this study was to use phase-contrast MRI to evaluate the influence of various breathing maneuvers on the hemodynamics of the pulmonary and systemic arterial circulation. Twenty-five volunteers were examined with phase-contrast MRI. Flow measurements were acquired in the aorta, pulmonary trunk, and left and right pulmonary arteries during deep, large-volume inspiratory breath-hold, expiratory breath-hold, and smooth respiration (no breath-hold). Parameters assessed were peak velocity, blood flow, velocity gradient, and acceleration time. Pulmonary blood flow and peak velocity were significantly reduced during inspiratory breath-hold and expiratory breath-hold compared with no breath-hold (p < 0.01). Pulmonary velocity gradient in inspiratory breath-hold was significantly (p </= 0.01) lower than in expiratory breath-hold and no breath-hold. There was no difference in velocity gradient between expiratory breath-hold and no breath-hold. Peak velocity in the aorta was lowest with no breath-hold. Velocity gradient was highest in expiratory breath-hold, and no breath-hold had the smallest SD. Acceleration time in the pulmonary trunk showed no difference between inspiratory breath-hold, expiratory breath-hold, and no breath-hold. Blood flow distribution to the left (45-47%) and to the right (53-55%) lung was not influenced by breathing maneuver. Measurements during smooth respiration showed the smallest SD. Therefore, no-breath-hold measurements should be considered for assessment of hemodynamics in clinical practice.

Pulmonary Artery Adventitial Fibroblasts Cooperate with Vasa Vasorum Endothelial Cells to Regulate Vasa Vasorum Neovascularization: A Process Mediated by Hypoxia and Endothelin-1

The precise cellular and molecular mechanisms regulating adventitial vasa vasorum neovascularization, which occurs in the pulmonary arterial circulation in response to hypoxia, remain unknown. Here, using a technique to isolate and culture adventitial fibroblasts (AdvFBs) and vasa vasorum endothelial cells (VVECs) from the adventitia of pulmonary arteries, we report that hypoxia-activated pulmonary artery AdvFBs exhibited pro-angiogenic properties and influenced the angiogenic phenotype of VVEC, in a process of cell-cell communication involving endothelin-1 (ET-1). We demonstrated that AdvFBs, either via co-culture or conditioned media, stimulated VVEC proliferation and augmented the self-assembly and integrity of cord-like networks that formed when VVECs where cultured on Matrigel. In addition, hypoxia-activated AdvFBs produced ET-1, suggesting a paracrine role for this pro-angiogenic molecule in these processes. When co-cultured on Matrigel, AdvFBs and VVECs self-assembled into heterotypic cord-like networks, a process augmented by hypoxia but attenuated by either selective endothelin receptor antagonists or oligonucleotides targeting prepro-ET-1 mRNA. From these observations, we propose that hypoxia-activated AdvFBs exhibit pro-angiogenic properties and, as such, communicate with VVECs, in a process involving ET-1, to regulate vasa vasorum neovascularization occurring in the adventitia of pulmonary arteries in response to chronic hypoxia.

Quality Improvement Guidelines for the Treatment of Lower Extremity Deep Vein Thrombosis with Use of Endovascular Thrombus Removal

Quality Improvement Guidelines for the Treatment of Lower Extremity Deep Vein Thrombosis with Use of Endovascular Thrombus Removal

Phenotypic Diversity of the Lung Vasculature in Experimental Models of Metastases

In vivo phage display is a screening method in which peptides homing to specific vascular beds are selected after IV administration of a random peptide library. This strategy has revealed a vascular address system that allows tissue-specific targeting of normal blood vessels and angiogenesis-related targeting of tumor blood vessels by selected peptides. Many vascular receptors or "addresses" targeted by homing peptides have been identified. One such vascular receptor of normal lung endothelium is membrane dipeptidase (MDP), which was found by in vivo phage display to bind the tripeptide motif gly-phe-glu (GFE). Our studies with GFE peptide and lung vasculature suggest that MDP mediates cancer cell adhesion to lung vasculature and the development of lung metastases, but that MDP is not present in the vasculature of lung metastases. MDP appears to occupy a vascular distribution that is similar to the pulmonary artery circulation. These results demonstrate the promise of defining critical functional and anatomic characteristics of endothelial cells in lung and other organs by in vivo phage display.