Pulmonary hypertension and arterial changes in calves with a systemic-to-left pulmonary artery connection

The pathogenic mechanisms by which increased pressure and flow lead to pulmonary vascular disease are poorly understood, especially in newborns. To study the pathophysiological correlations and timing of the development of structural changes in response to high flow in nonhypoxic neonates, a model of high pulmonary flow was developed in newborn calves by anastomosis of the isolated left pulmonary artery (LPA) to the aorta. LPA pressure and flow increased acutely. LPA pressure reached near-systemic levels by 10 wk, whereas LPA flow was maximally increased at 1 mo before decreasing in several calves. Right pulmonary arterial pressure remained normal, and ventricular hypertrophy did not develop. Morphometric evaluation of the left lung demonstrated decreased arteriolar diameter, increased medial thickness, muscularization of arterioles at the bronchoalveolar junction, luminal obliteration of small arteries, and dilation lesions. The LPA pressure and vascular changes were greater and developed over a shorter time period than did prior models of nonhypoxic flow-induced pulmonary vascular changes. Lesser degrees of decreased arteriolar diameter and muscularization of small vessels were seen in the right lung, indicating a difference in the vascular response to moderately increased flow vs. increased pressure and flow. Thus, calves with an isolated LPA-to-aortic anastomosis simulate the hemodynamic and pulmonary vascular changes seen in newborns with congenital heart defects. Such calves may serve as models to assess effects of mechanical stresses on a newborn's vasculature.

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Unintended Pulmonary Artery Ligation during PDA Ligation

The Heart Surgery Forum ◽

10.1532/hsf.1449 ◽

2016 ◽

Vol 19 (4) ◽

pp. 187 ◽

Cited By ~ 2

Author(s):

Dohun Kim ◽

Si-Wook Kim ◽

Hong-Ju Shin ◽

Jong-Myeon Hong ◽

Ji Hyuk Lee ◽

...

Keyword(s):

Pulmonary Artery ◽

Ductus Arteriosus ◽

Left Lung ◽

Left Pulmonary Artery ◽

Chest Ct ◽

Mechanical Ventilator ◽

Artery Ligation ◽

Ventilator Support ◽

Surgical Ligation ◽

Emergent Operation

A 10-day-old boy was transferred to our hospital due to tachypnea. Patent ductus arteriosus (PDA), 4.8 mm in diameter, with small ASD was diagnosed on echocardiography. Surgical ligation of the ductus was performed after failure of three cycles of ibuprofen. However, the ductus remained open on routine postoperative echocardiography on the second postoperative day, and chest CT revealed inadvertent ligation of the left pulmonary artery (LPA) rather than the PDA. Emergent operation successfully reopened the clipped LPA and ligated the ductus on the same (second postoperative) day.<br />Mechanical ventilator support was weaned on postoperative day 21, and the baby was discharged on postoperative day 47 with a normal left lung shadow.

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The pulmonary vasculature in a neonatal porcine model with increased pulmonary blood flow and pressure

Cardiology in the Young ◽

10.1017/s1047951101000543 ◽

2001 ◽

Vol 11 (4) ◽

pp. 420-430 ◽

Cited By ~ 4

Author(s):

Elisabeth V. Stenbøg ◽

Daniel A. Steinbrüchel ◽

Anne Bloch Thomsen ◽

Ulrik Baandrup ◽

Lene Heickendorff ◽

...

Keyword(s):

Blood Flow ◽

Pulmonary Artery ◽

Vascular Disease ◽

Pulmonary Blood Flow ◽

Left Pulmonary Artery ◽

Pulmonary Vasculature ◽

Pulmonary Vascular Disease ◽

Systolic Pulmonary Arterial Pressure ◽

Pulmonary Arterial ◽

Circulating Levels

Introduction: Hypertension and hyperperfusion of the pulmonary vascular bed in the setting of congenital cardiac malformations may lead to progressive pulmonary vascular disease. To improve the understanding of the basic mechanisms of this disease, there is a need for clinically relevant animal models which reflect the disease process. Material and Results: We randomly allocated 45 newborn pigs, at the age of 48 hrs, to groups in which there was either construction of a 3 mm central aorto-pulmonary shunt, undertaken in 9, or ligation of the left pulmonary artery, achieved in 13. Controls included sham operations in 13, or no operations in 10 pigs. Follow-up was continued for three months. The interventions were compatible with survival in most pigs. The shunts resulted in an acute 85% increase in systolic pulmonary arterial pressure, and a more than twofold increase in pulmonary blood flow. By three months of age, nearly all shunts had closed spontaneously, and haemodynamics were normal. Ligation of the left pulmonary artery resulted in a normal total pulmonary blood flow, despite only the right lung being perfused, and a 33% increase in systolic pulmonary arterial pressure. These haemodynamic changes were maintained throughout the period of study. In both groups, histomorphometry revealed markedly increased muscularity of the intra-acinar pulmonary arteries. Circulating levels of endothelin were normal in the shunted animals, and elevated in those with ligation of the left pulmonary artery. Conclusion: In neonatal porcine models of pulmonary vascular disease, created by construction of 3 mm central aorto-pulmonary shunts and ligation of one pulmonary artery, we observed histopathological changes of the pulmonary vasculature similar to early hypertensive pulmonary vascular disease in humans. Elevated circulating levels of endothelin were associated with abnormal haemodynamics rather than abnormal pathology. These findings could be valuable for future studies on the pathogenesis of hypertensive pulmonary vascular disease associated with congenital cardiac malformations.

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Abstract 12430: Vicious Circle Between Progressive Right Ventricular Dilatation and Pulmonary Regurgitation in Patients After Tetralogy of Fallot Repair? Right Heart Enlargement Promotes Flow Reversal in the Left Pulmonary Artery

Circulation ◽

10.1161/circ.132.suppl_3.12430 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Atsuko Kato ◽

Christian Drolet ◽

Shi-Joon Yoo ◽

Andrew Redington ◽

Lars Grosse-Wortmann

Keyword(s):

Pulmonary Artery ◽

Tetralogy Of Fallot ◽

Left Lung ◽

Pulmonary Regurgitation ◽

Left Pulmonary Artery ◽

Flow Reversal ◽

Left Hemithorax ◽

Forward Flow ◽

Lung Area ◽

The Right

Introduction: The left pulmonary artery (LPA) contributes more than the right (RPA) to total pulmonary regurgitation (PR) in patients after tetralogy of Fallot (TOF) repair, but the mechanism of this difference is not well known. We hypothesized that unilaterally increased pulmonary vascular resistance (PVR), resulting from lung compression by the enlarged and levorotated heart leads to greater PR in the LPA. This study aimed to analyze the interplay between heart and lung size, mediastinal geometry, and differential PR. Methods: This is a single-center retrospective analysis of 50 magnetic resonance studies in patients after TOF repair. Patients with more than mild discrete branch pulmonary artery stenosis were excluded. Blood flow was measured by phase-contrast velocity encoding within the branch pulmonary arteries. On the axial image with the largest total cardiac surface area, cardiac angle (α) between the thoracic anterior-posterior line and the interventricular septum, right and left lung areas as well as right and left hemithorax areas were measured (Figure). Results: There was no difference in LPA and RPA diameters. The LPA showed significantly less total forward flow (p=0.04), smaller net forward flow (p=<0.001), and greater RF (p=0.001) than the RPA. Left lung area was smaller than the right (p<0.001). RVEDVi correlated with LPA RF (R=0.48, p<0.001), but not with RPA RF. Larger RVEDVi correlated with a larger α angle (R=0.46, p<0.001), i.e. a more leftward cardiac axis and with smaller left lung area (R=-0.58, p<0.001). LPA RF, but not RPA RF, correlated inversely with left lung area indexed to the left hemithorax area (R=-0.34, p=0.02). Conclusions: An enlarged and levorotated heart - as a result of PR - is associated with smaller left lung size, and augments diastolic flow reversal in the LPA, presumably via increased left PVR. By imposing a further volume load on the RV, LPA regurgitation may thus close a positive feed-back loop of PR and RV dilatation.

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Effect of pulmonary artery occlusion and reperfusion on extravascular fluid accumulation

Journal of Applied Physiology ◽

10.1152/jappl.1981.50.1.102 ◽

1981 ◽

Vol 50 (1) ◽

pp. 102-106 ◽

Cited By ~ 18

Author(s):

P. S. Barie ◽

T. S. Hakim ◽

A. B. Malik

Keyword(s):

Pulmonary Artery ◽

Water Content ◽

Left Atrial ◽

Left Lung ◽

Weight Ratio ◽

Dry Weight ◽

Left Pulmonary Artery ◽

Artery Occlusion ◽

Lung Water ◽

The Right

We determined the effect of pulmonary hypoperfusion on extravascular water accumulation in anesthetized dogs by occluding the left pulmonary artery for 3 h and then reperfusing it for 24 h. The lung was reperfused either at normal left atrial pressure (Pla) or during increased Pla induced by a left atrial balloon. In each case the extravascular water content-to-bloodless dry weight ratio (W/D) of the left lung was compared with that of the right lung. The W/D of the left lung of 3.26 +/- 0.49 ml/g was not significantly different from the value of 2.87 +/- 0.37 for the right lung after the reperfusion at normal Pla. However, the W/D of the left lung of 5.10 +/- 0.38 ml/g was greater (P less than 0.05) than the value of 4.42 +/- 0.34 for the right lung after reperfusion at Pla of 25 Torr. This difference could not be prevented by pretreatment with heparin, suggesting that the increase in lung water content was not due to activation of intravascular coagulation secondary to stasis occurring during the occlusion. Because the left lung was more edematous than the right one, even though both lungs had been subjected to the same increase in Pla, the results suggest that a period of pulmonary hypoperfusion causes an increase in the interstitial protein concentration.

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The role of CXCR2 in systemic neovascularization of the mouse lung

Journal of Applied Physiology ◽

10.1152/japplphysiol.00037.2007 ◽

2007 ◽

Vol 103 (2) ◽

pp. 594-599 ◽

Cited By ~ 14

Author(s):

Jesús Sánchez ◽

Aigul Moldobaeva ◽

Jessica McClintock ◽

John Jenkins ◽

Elizabeth Wagner

Keyword(s):

Blood Flow ◽

Pulmonary Artery ◽

Left Lung ◽

Neutralizing Antibody ◽

Left Pulmonary Artery ◽

Endothelial Cell Proliferation ◽

Antibody Treatment ◽

Pulmonary Artery Obstruction ◽

Artery Obstruction ◽

Deficient Mice

We previously showed increased expression of the ELR+, CXC chemokines in the lung after left pulmonary artery obstruction. These chemokines have been shown in other systems to bind their G protein-coupled receptor, CXCR2, and promote systemic endothelial cell proliferation, migration, and capillary tube formation. In the present study, we blocked CXCR2 in vivo using a neutralizing antibody and also studied mice that were homozygous null for CXCR2. To estimate the extent of neovascularization in this model, we measured systemic blood flow to the left lung 14 days after left pulmonary artery ligation (LPAL). We found blood flow significantly reduced (67% decrease) with neutralizing antibody treatment compared with controls. However, blood flow was not altered in the CXCR2-deficient mice compared with wild-type controls after LPAL. To test for ligand availability, we measured macrophage inflammatory protein (MIP)-2 in lung homogenates after LPAL, because this is the predominant CXC chemokine previously shown to be increased after LPAL ( 22 ). MIP-2 protein was two- to fourfold higher in the left lung relative to the right lung in all treatment groups 4 h after LPAL and this increase did not differ among groups. We speculate that the CXCR2-deficient mice have compensatory mechanisms that mitigate their lack of gene expression and conclude that CXCR2 contributes to chemokine-induced systemic angiogenesis after pulmonary artery obstruction.

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Left Lung and Pulmonary Artery Hypoplasia: A Rare Case of Hemoptysis

European Journal of Case Reports in Internal Medicine ◽

10.12890/2020_001490 ◽

2020 ◽

Author(s):

Guiomar Pinheiro ◽

Ana Margarida Alves ◽

Isabel Neves ◽

Teresa Sequeira

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Artery ◽

Pulmonary Hypoplasia ◽

Left Lung ◽

Left Pulmonary Artery ◽

Pulmonary Infections ◽

Rare Congenital Disorder ◽

History Of ◽

Pulmonary Artery Hypoplasia

Pulmonary hypoplasia or agenesis is a rare congenital disorder that results in lung underdevelopment. This disease is usually found in children but rarely encountered in adults. We describe the case of an 84-year-old woman diagnosed with a unilateral pulmonary hypoplasia presenting simultaneously with left pulmonary artery hypoplasia. Due to this condition, the patient had a lifelong history of pulmonary infections that resulted in several bronchiectases in the affected lung. Moreover, the pulmonary artery hypoplasia led to the development of pulmonary hypertension and collateral circulation causing hemoptysis, giving rise to the patient attending the emergency department. Although we were able to medically manage the hemoptysis, it can be fatal and require surgical intervention. Hence, an early diagnosis is essential so that appropriate follow-up and prompt prevention and treatment of complications, such as pulmonary infections, hemoptysis and pulmonary hypertension, are achieved.

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Role of ROS in ischemia-induced lung angiogenesis

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00002.2010 ◽

2010 ◽

Vol 299 (4) ◽

pp. L535-L541 ◽

Cited By ~ 43

Author(s):

Julie Nijmeh ◽

Aigul Moldobaeva ◽

Elizabeth M. Wagner

Keyword(s):

Pulmonary Artery ◽

Left Lung ◽

Left Pulmonary Artery ◽

Wild Type ◽

Systemic Blood Flow ◽

Artery Ligation ◽

Underlying Mechanisms ◽

Pulmonary Artery Obstruction ◽

Artery Obstruction

Pulmonary artery obstruction and subsequent lung ischemia have been shown to induce systemic angiogenesis despite preservation of normoxia. The underlying mechanisms, however, remain poorly understood. In a mouse model of lung ischemia induced by left pulmonary artery ligation (LPAL), we showed previously, the formation of a new systemic vasculature to the ischemic lung. We hypothesize that LPAL in the mouse increases reactive oxygen species (ROS) production, and these molecules play an initiating role in subsequent lung neovascularization. We used oxidant-sensitive dyes (DHE and H2DCF-DA) to quantify ROS and measured the antioxidant-reduced glutathione (GSH) and its oxidized form (GSSG) as indicators of ROS levels after LPAL. The magnitude of systemic neovascularization was determined by measuring systemic blood flow to the left lung with radiolabeled microspheres 14 days after LPAL. An increase in ROS was observed early (30 min: 55% increase in H2DCF-DA) after LPAL, with a return to baseline by 24 h. GSH/GSSG was decreased (∼50%) 4 h after LPAL, suggesting earlier ROS upregulation. Mice treated with the antioxidant N-acetylcysteine showed attenuated angiogenesis (62% of wild-type LPAL), and mice lacking Nrf2, a transcription factor important for antioxidant synthesis, resulted in increased neovascularization (207% of wild-type LPAL). Overall, GSH/GSSG was inversely associated with the magnitude of neovascularization. These results demonstrate that LPAL induces an early and transient ROS upregulation, and ROS appear to play a role in promoting ischemia-induced angiogenesis.

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Abstract 15542: Late Pulmonary Hypertension in Surgically Palliated D-transposition of the Great Arteries: A 55-year Review

Circulation ◽

10.1161/circ.142.suppl_3.15542 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Blair Suter ◽

Dylan Hall ◽

Eric S Ebenroth ◽

Larry W Markham ◽

Michael Johansen

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Artery ◽

Late Onset ◽

Systolic Dysfunction ◽

Left Lung ◽

Treatment Strategies ◽

Lung Hypoplasia ◽

Pulmonary Vascular Disease ◽

Complete Evaluation ◽

Lost To Follow Up

Introduction: Pulmonary hypertension (PH) has been described following surgical palliation for transposition of the great arteries (D-TGA). While early pulmonary vascular disease is associated with late repair, the increasing prevalence of late PH has been observed following the intra-atrial baffle procedure (ABP), Mustard/Senning. A previous study from our institution identified patients with precapillary PH. More recent studies have described predominately postcapillary PH, suggesting multiple, differing mechanisms for this complication. Hypothesis: While heart failure is a common complication following ABP and is associated with postcapillary PH, we hypothesize that precapillary PH can be identified in a subset of patients. Methods: A retrospective descriptive study was performed at a single institution. Using 6 th World Symposium on Pulmonary Hypertension definitions. PH was defined as a mean pulmonary artery pressure >20mmHg. Etiology of PH was defined as precapillary (≥3 Wood units) versus postcapillary (pulmonary artery wedge pressure >15 mmHg). Results: We reviewed 157 D-TGA patients following ABP, finding 33 patients with PH. Mean age at last evaluation was 36.6 (14-54) years. Current condition: 22 alive, 7 dead, and 4 lost to follow-up. Etiology of PH: 10 precapillary, 8 postcapillary, 8 mixed, 2 borderline PH, and 2 did not undergo catherization. Additionally, 2 patients had pulmonary venous baffle obstruction and 1 had left lung hypoplasia. Of patients with recent imaging, 21 of 25 had systemic RV systolic dysfunction on echocardiogram or MRI. Conclusions: Late-onset PH in D-TGA following ABP is a significant long-term complication and warrants vigilant surveillance. This highlights the limitations of imaging and need for catheterization for complete evaluation. In this study, we observed precapillary PH in a majority of patients with PH, which differs from some previous studies. Identifying the etiology of PH could drastically alter treatment strategies and has implications for transplant consideration. Further studies are needed to identify the clinical attributes that contribute to this process.

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Microvascular injury distal to unilateral pulmonary artery occlusion

Journal of Applied Physiology ◽

10.1152/jappl.1981.51.4.845 ◽

1981 ◽

Vol 51 (4) ◽

pp. 845-851 ◽

Cited By ~ 17

Author(s):

R. L. Johnson ◽

S. S. Cassidy ◽

M. Haynes ◽

R. L. Reynolds ◽

W. Schulz

Keyword(s):

Pulmonary Artery ◽

Left Lung ◽

Left Pulmonary Artery ◽

Artery Occlusion ◽

Diffusing Capacity ◽

Pulmonary Capillary Blood Flow ◽

Pulmonary Capillary ◽

Pulmonary Capillary Blood ◽

Rebreathing Method ◽

Unilateral Pulmonary Artery Occlusion

We explored three questions: 1) does edema fluid accumulate distal to temporary unilateral pulmonary artery occlusion (TUPAO); 2) if so how rapidly does it accumulate; and 3) how is it affected by positive end-expiratory pressure (PEEP)? Using a tracheal divider we measured pulmonary capillary blood flow (Qc), tissue volume (Vt), and diffusing capacity (DLCO) in each lung with a rebreathing method. After control measurements in 12 dogs, the left pulmonary artery was occluded and measurements were repeated at intervals during 4 h of occlusion and 30 min after release of the occlusion. Six of the dogs were ventilated with 10 cmH2O PEEP. Finally the lungs were removed, weighed, and fixed for histology. TUPAO caused a 29% increase in Vt of the left lung without PEEP and a 59% increase with PEEP. After release of the occlusion, Qc and DLCO in the left lung returned to control levels within 30 min in dogs not on PEEP but remained depressed in dogs ventilated with PEEP even though PEEP was removed. At postmortem the left lung weighed more than expected in both groups of dogs but was significantly heavier in those on PEEP. Histology confirmed bronchovascular cuffing with edema and hemorrhage.

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