Ann Thorac Surg 2007;84:1645-1650. doi:10.1016/j.athoracsur.2007.05.094
© 2007 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Left Pulmonary Artery Sling Complex: Computed Tomography and Hypothesis of Embryogenesis
Shyh-Jye Chen, MD, PhDa,
Wen-Jeng Lee, MDa,
Ming-Tai Lin, MDb,
Jou-Kou Wang, MD, PhDb,
Chung-I. Chang, MDc,
Ing-Sh Chiu, MD, PhDc,
Mei-Hwan Wu, MD, PhDb,*
a Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
b Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
c Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
Accepted for publication May 29, 2007.
* Address correspondence to Dr Wu, Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, 7 Chung-Shan South Rd, Taipei, 100, Taiwan (Email: wumh{at}ntu.edu.tw).
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Abstract
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Background: We retrospectively reviewed cases of left pulmonary artery (LPA) sling complex with computed tomography to explore its possible meaning in embryogenesis.
Methods: Eighteen children (6 girls and 12 boys aged 5 days to 17.5 years; mean, 1.5 years) were identified as having LPA sling during the period of October 1996 to March 2006. Another 2,364 cardiac computed tomography scans that had no LPA sling were included as control. The associated bronchopulmonary and vascular anomalies were identified. Chi-square tests were used to compare the probabilities of coexistence of these anomalies, with or without LPA sling.
Results: All patients with LPA sling presented with tracheal stenosis (100%), and there was a high incidence of combined right tracheal bronchus (22%), underdeveloped right lung (22%), persistent left superior vena cava (22%), and left patent ductus arteriosus (39%). These associated anomalies were more highly associated with subjects who had LPA sling than with those who did not (p < 0.01).
Conclusions: Owing to the spatial coexistence of LPA sling with the associated anomalies in the embryonic foregut mesoderm, we propose that a "space available" hypothesis in the local environment appears to be important in the embryogenesis of an LPA sling complex.
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Introduction
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The pulmonary artery is composed of a portion that is derived from the ventral sixth branchial arch, and a portion that is derived from the postbranchial vessel. Normally, the left postbranchial vessels connect to the left sixth branchial arch to form the left pulmonary artery (LPA), and the right postbranchial vessels capture a major vascular supply from the right sixth branchial arch to make a right pulmonary artery (RPA) [1]. The lungs originate as a pair of lung buds from the foregut endoderm. As the primitive trachea lengthens, the lung buds are carried progressively more caudal until they reach their definitive position in the thorax. These buds develop by branching sequentially until terminal bronchiole and terminal sacs (future alveoli) are formed [2]. Both of the developing primitive pulmonary arteries and the primitive respiratory system are located at the same embryonic foregut mesoderm, and the development of the lungs interacts with the development of the pulmonary vessels [3–5].
Left pulmonary artery sling, first described by Glaevecke and Doehle in 1897 [6], is a rare congenital anomaly in which the pulmonary artery to the left lung originates from the proximal portion of the pulmonary artery to the right lung. Initially, it runs to the right side and passes behind the right main bronchus and then from right to left, dorsal to the trachea but anterior to the esophagus, to reach the hilum of the left lung (Fig 1a). The LPA sling is frequently associated with tracheal anomalies, congenital heart disease, and lung abnormalities [7, 8]. The development of noninvasive imaging modalities such as computed tomography (CT), ultrasonography, and magnetic resonance imaging has led to increased reports of this entity [9]. In this report, we describe the largest series of children with LPA sling that was evaluated with CT. The purpose of our retrospective study was to review the LPA sling complex with CT to explore the meaning of its embryogenesis.
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Fig 1. Computed tomography findings in the diagnosis of (a) left pulmonary artery sling (case 14), (b) tracheal stenosis (arrows; case 15), (c) right tracheal bronchus (arrow; case 2) and low tracheal stenosis (arrowheads), (d) right lung agenesis (case 11), (e) right lung hypoplasia (case 13), (f) left patent ductus arteriosus (arrows; case 9), and (g) persistent left superior vena cava (arrow; case 7, who received the contrast injection in the left hand). (A = ascending aorta; D = descending aorta; P = pulmonary trunk.)
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Patients and Methods
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Patients
The study protocol was approved by the local Ethics Committee, and written informed consent was obtained from all patients or their guardians, as appropriate. Patients who underwent cardiac CT examinations to obtain information needed for further management of congenital heart disease were identified in a 2,000-bed tertiary referral general hospital from October 1996 to March 2006. Of all the cardiac CT examinations during the study period, 2,382 subjects were identified with situs solitus. We excluded patients who had bilateral right-sidedness because in heterotaxy subjects, bilateral pulmonary arteries are morphologically RPA, which are unsuitable for inclusion in analyses that focus on the morphologically LPA of a LPA sling. Of these 2,382 subjects, 18 patients (6 girls and 12 boys aged 5 days to 17.5 years; mean, 1.5 years; median, 2 months) showed the diagnosis of LPA sling. The medical records of these patients were also reviewed for demographic and clinical variables. A summary of patients’ clinical data and their associated anomalies is listed in Table 1.
CT Scanning Protocol and Image Analysis
Subjects underwent contrast-enhanced cardiac CT examinations (C150-L [Imatron, South San Francisco, California] from October 1996 to September 2003; and LightSpeed 16 [General Electric Medical Systems, Milwaukee, Wisconsin] from September 2003 to March 2006), with electrocardiographic gating, and all images were obtained at the end-diastolic phase of the cardiac cycle; slice thickness was 3 mm when using the C150-L scanner and 0.625 mm when using the LightSpeed 16 scanner. Computed tomography was performed beginning at the level of the lung apex, to the cardiac apex, without gaps. The table increment was 3 mm when using the C150-L scanner and 0.625 mm for all patients evaluated using the LightSpeed 16 scanner. The matrix of the reconstructed axial image was 512 x 512 pixels. Nonionic iodinated contrast medium (Ultravist 370; Schering, Berlin, Germany), 2 to 3 mL/kg, was delivered using a power injector in all patients. Image acquisition was delayed 20 s and 25 s from the start of contrast injection in neonates and children, respectively. Patients were free breathing during the examination. Patients less than 5 years of age were routinely sedated with chloral hydrate, 50 mg/kg in neonates and 50 to 75 mg/kg in children to age 2 before imaging.
Two radiologists with 12 and 5 years of experience in cardiac computed tomography, retrospectively assessed the CT images to confirm the anomalies of interest. They were blinded to each other’s findings and to the results of the cardiac echocardiography or angiography. Retrospective review of the cardiac catheterizations and echocardiography findings was performed by a pediatric cardiologist with 6 years of experience in assessing pediatric cardiac imaging. Differences between cardiac angiograms and echocardiography from the CT evaluations were reviewed again and finally resolved by consensus of the three assessors after all images were reviewed together in a separate subsequent session.
The following are the diagnostic criteria used. Tracheal stenosis was defined as a segment of the trachea that had a measured diameter on axial CT image less than the 95% confidence intervals of normal children (Fig 1b) [9, 10]. The diagnosis of complete "O" rings of a trachea was defined as absence of the soft membranous part of the trachea at its dorsal part on bronchoscopy or during surgery. Right tracheal bronchus was defined as a right upper lobe bronchial segment stemming from the lateral wall of the trachea superior to the carina (Fig 1c) [9]. Underdeveloped right lung was defined as smaller volume of the right lung than the left one, including lung agenesis (Fig 1d) or hypoplasia of the right lung (Fig 1e). The RPA, right pulmonary vein, and right bronchial tree were totally absent on CT images in right lung agenesis. In case of hypoplasia of the right lung, the right lung and pulmonary artery were smaller than those on the left side. Left patent ductus arteriosus (PDA) is shown on CT images as a connecting vessel between the proximal descending aorta and the proximal LPA (Fig 1f). Persistent left superior vena cava (PLSVC) was defined as a vertical vessel coming from the union of the left subclavian vein and left jugular vein, downward toward the coronary sinus, with its course in the left atrioventricular groove, at its lower portion (Fig 1g).
Statistical Analyses
Descriptive statistics were used to describe the frequency (percentage) of each anomaly. In the same study period, associated anomalies of the other 2,364 situs solitus subjects who had no LPA sling were used as control to the coexisting anomalies in these 18 children with LPA sling. The 
2 test was used for statistical analysis to compare the probabilities of coexistence of the associated anomalies occurring with or without the LPA sling. All p values less than 0.01 were considered statistically significant. All statistical analyses were performed by using commercially available software (Excel 2002 SP3 for Windows; Microsoft, Seattle, Washington).
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Results
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The numbers of patients with and without left pulmonary artery slings and the associated anomalies are shown in Table 2. Eleven patients underwent reimplantation of the LPA; the finding in the operative field was consistent with CT.
Tracheal stenosis was associated with 100% of the patients with LPA sling. The stenotic lengths ranged from 9 to 30 mm (mean, 18 mm). Surgical (n = 11) or bronchoscopic (n = 10) confirmations were made in 16 patients. During the same period, only 16 other patients with congenital heart disease but without LPA sling had tracheal stenosis (16 of 2,382; 0.7%). It shows a highly significant association between LPA sling and tracheal stenosis (p < 0.000001).
We found right tracheal bronchus in 4 patients with LPA sling (4 of 18; 22%). Another 84 patients, who had congenital heart disease but did not have LPA sling, had right tracheal bronchus (84 of 2,364; 3.6%) during the same period. It shows a highly significant association between LPA sling and right tracheal bronchus (p < 0.0001).
Three children with LPA sling had right lung agenesis (3 of 18; 17%). Among the remaining 15 patients with LPA sling, 1 had hypoplasia of the right lung. Thus, the rate of LPA sling among patients with underdeveloped right lung was 4 of 18 (22%). There were another 10 patients (10 of 2,364; 0.4%) with congenital heart disease but without LPA sling who had right lung agenesis (n = 3) or right lung hypoplasia (n = 7) during the study. It shows a highly significant association between LPA sling and underdeveloped right lung (p < 0.000001).
Left PDA was the most common cardiovascular anomaly (7 of 18; 39%) found in association with LPA sling among the patients. There were another 232 patients with congenital heart disease who had left PDA (232 of 2,367; 9.8%) without LPA sling during the study period. It shows a highly significant association between LPA sling and PDA (p < 0.0001).
The rate of combined PLSVC among the patients with LPA sling was high (4 of 18; 22%). During the study period, we identified another 175 patients with congenital heart disease who did not have LPA sling, but had PLSVC (175 of 2,365; 7.4%). It shows a weak significant association between LPA sling and PLSVC (p < 0.02).
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Comment
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Left pulmonary artery sling is a rare anomaly that is increasingly recognized on noninvasive imaging modalities. Recognition of this anomaly during imaging investigations should alert the clinician to the possibility of associated malformations and their possible impact on clinical management [11]. Interestingly, in embryos, these primitive structures (respiratory diverticulum, bronchial buds, lung buds, sixth branchial arch, and left common cardinal vein) all present in the same space of the embryonic foregut mesoderm. From our data, we presented strong correlation among them.
It is believed that the cause of LPA sling is multifactorial [12]. There is evidence of genetic-related factors such as the case report of LPA sling in identical twins [13], and in patients with trisomies 18 [14] and 21 [13, 15]. Pu and colleagues [8] hypothesized that if the left postbranchial vessels cannot connect to the left sixth branchial arch, then they might capture a vascular supply from the most nearby major artery. When a connection is made to the right sixth branchial arch through the embryonic peritracheal mesenchyme between the trachea and the esophagus as well as caudal to the developing tracheal bronchial tree rather than cephalic, an LPA sling results [8].
Relationship Between LPA Sling and Tracheal Stenosis
Before the period during which the primitive pulmonary artery develops in the early embryonic stage, the respiratory diverticulum from the foregut is forming just posterior and inferior to the intended sixth branchial arch [4]. Regnier and coworkers [16] reported a severe reduction in the diameter of the primitive trachea in congenital tracheal stenosis. Such a reduction extended below the tracheal bifurcation to the right and left primary bronchi [16]. All our patients with LPA sling had tracheal stenosis. Therefore, we think that they had hypoplastic primitive upper respiratory trees during embryogenesis. In that, the embryonic peritracheal mesenchyme is widened that provides a roomy space for the left postbranchial vessels to approach the right ventral sixth branchial arch.
Relationship Between LPA Sling and Right Tracheal Bronchus
As the lung buds divide repeatedly, they form the bronchial tree. The pattern of branching of the lung buds are guided by signals modulated by the surrounding mesenchyme [17]. Tracheal bronchus occurs in approximately 2% of the general population [18]. In our present study, tracheal bronchus occurred at the rate of 22%. With the essence of "space availability," we think our patients with LPA sling likely had early branching of the right upper bronchus during embryogenesis, leaving a wider space around the lower developing primitive trachea. Such development leaves more space available around the primitive carina, which consequently increases the chance of the left postbranchial pulmonary vessel to approach the right ventral sixth branchial arch. And since the primitive RPA is developing along with the proximal segment of the early branching tracheal bronchus, the proximal portion of the primitive RPA maybe also be upward located a little than that in the normal tracheal bronchial tree, which consequently increases the chance of the left postbranchial pulmonary vessel to approach the right ventral sixth branchial arch caudally.
Relationship Between LPA Sling and Underdeveloped Right Lung
The lungs originate as a pair of lung buds from the foregut endoderm and interact with the developing pulmonary vessels [4, 5, 19]. The early lung buds are deriving capillaries from the primitive systemic circulation, but as the lungs grow, these primitive systemic vessels are programmed to regress. In later lung development, a well-perfused capillary bed is essential for alveoli formation. Complete arrest of the pulmonary artery supply results in agenesis of the lung [5, 20]. Based on our results, we think that the right postbranchial primitive pulmonary vessel was prone to failure on competition with the left postbranchial primitive pulmonary vessel to fuse to the ventral, right, sixth branchial arch in the case of LPA sling. Finally, the right lung bud would get no perfusion and would become ischemic, resulting in right lung agenesis when its primitive vascular network connected to the dorsal aorta is programmed to regress.
Relationship Between PDA, PLSVC, and LPA Sling
Our data also show that the common cardiovascular lesions associated with LPA sling are PLSVC and PDA [7, 21]. Continuing with our "space availability" theory, we think that because the space for the course of the intended proximal LPA in patients with LPA sling is spared in the early embryo development, it would leave roomier left, peritracheal splanchnic mesenchyme for the unrestricted growth of the primitive, left, sixth branchial arch and the left, common cardinal vein, consequently increasing chance of resulting in formation of PDA and PLSVC, respectively (Fig 2).
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Fig 2. Models of the (a) normal and (b) left pulmonary artery (LPA) sling vasculature, airway and esophagus in the left, anterior, oblique cephalic view, with half transparent volume rendering of volumetric data from computed tomography of 2 subjects (case 7 and another normal subject matched for age). The space (#) between the trachea (T) and the esophagus (E) is wider in the patient with LPA sling (arrow) than in the normal subject. The initial space accommodating normal LPA development is spared in patients with LPA sling, and then develops into patent ductus arteriosus (@) and middle portion of the persistent left superior vena cava (PLSVC). (Ao = aorta; LPA = left pulmonary artery; PT = pulmonary trunk; RSVC = right superior vena cava.)
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Study Limitations
The following study limitations must be acknowledged. Our study was based on the data from CT after the patients were born. The retrospective research design is the limitation. All discussed structures were already there. It is hard to observe the proposed process at different time points of human embryo development. Clearly, more data from developmental embryology that focuses on the embryogenesis of the pulmonary artery, airway, lungs, and their reciprocal interactions are needed. Additionally, PDA was more frequent in preterm babies and babies less than 1 week of age. In our study, we had 5 patients who were preterm, and 2 of them had PDA. Moreover, all of our 3 newborn babies younger than 1 week of age had PDA. Such an age distribution in our study population could interfere with the analysis of the coexistence of the LPA sling with PDA.
In conclusion, we propose a stepwise "space available" hypothesis in the local environment appears to be important in embryogenesis of an LPA sling complex. Clinically, the association between the LPA sling and tracheal stenosis is so strong that the discovery of one of these anomalies is indication to actively search for the other [22]. Traditional intervention always focuses on the reimplantation of the LPA sling to relieve external compression on the lower trachea in expectation of the recovery of the diameter of the stenotic segment. However, full recovery of the stenotic trachea did not occur after LPA reimplantation in all of our surviving patients (n = 7) who were monitored with CT imaging after corrective surgery (Fig 3). After this study, we consider the stenotic trachea requires reconstruction in symptomatic patients, because the stenosis is primary, consistent with some reported literatures [23–25]. Therefore, airway reconstruction and reimplantation of the LPA in LPA sling complex are of equal importance.
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Fig 3. This patient (case 14) was diagnosed with a left pulmonary artery (LPA) sling when he was 2 years, 2 months of age and underwent LPA reimplantation at that time. Three-dimensional reconstructed image of the left posterior cephalic oblique view reveals mild junctional stenosis of the reimplanted site (arrow) in the follow-up computed tomography study when he was 3 years old. The long segment tracheal stenosis (arrowheads) was still present.
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Acknowledgments
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This study was partially supported by a grant from the Children’s Cardiac Foundation of the Republic of China (CCF 04-03). We would like to thank Ritta Huang for her assistance with manuscript preparation.
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References
|
|---|
- Effmann EL. Development of the right and left pulmonary arteriesA microangiographic study in the mouse. Invest Radiol 1982;17:529-538.[Medline]
- Moore KL, Persaud TVN. The respiratory systemIn: Moore Kl, Persaud TVN, editors. The developing human: clinically oriented embryology. 6th ed.. Philadelphia: WB Saunders; 2000. pp. 259-262.
- Hislop AA. Airway and blood vessel interaction during lung development J Anat 2002;201:325-334.[Medline]
- Coffin JD, Poole TJ. Embryonic vascular development: immunohistochemical identification of the origin and subsequent morphogenesis of the major vessel primodia in quail embryos Development 1988;102:7735-7748.
- deMello DE, Reid LM. Embryonic and early fetal development of human lung vasculature and its functional implications Pediatr Dev Pathol 2002;3:439-449.
- Glaevecke D. Uber eine selltene angeborene Anomalie der Pulmonalarterie Muchen Med Wochenschr 1897;44:950.
- Gikonyo BM, Jue KL, Edwards JE. Pulmonary vascular sling: report of seven cases and review of the literature Pediatr Cardiol 1989;10:81-89.[Medline]
- Pu WT, Chung T, Hoffer FA, Jonas RA, Tal G. Diagnosis and management of agenesis of the right lung and left pulmonary artery sling Am J Cardiol 1996;78:723-727.[Medline]
- Berrocal T, Madrid C, Novo S, Gutierrez J, Arjonilla A, Gomez-Leon N. Congenital anomalies of the tracheobronchial tree, lung, and mediastinum: embryology, radiology, and pathology Radiographics 2004;24:e17.[Abstract/Free Full Text]
- Chen SJ, Shih TTF, Liu KL, et al. Measurement of tracheal size in children with congenital heart disease by computed tomography Ann Thorac Surg 2004;77:1216-1221.[Abstract/Free Full Text]
- Berdon WE. Ring, sling, and other things: vascular compression of the infant trachea updated from the midcentury to the millennium—the legacy of Robert E. Gross, MD, and Edward B. D. Newhauser, MD Radiology 2000;216:624-632.[Abstract/Free Full Text]
- Bamman JL, Byron HW, Woodrum DE. Aberrant Left pulmonary artery sling: clinical and embryologic factors Chest 1977;77:67-71.
- Westaby S, Dinwiddie R, Chrispin A, Stark J. Pulmonary artery sling in identical twins—report of two cases Thorac Cardiovasc Surg 1984;32:182-183.[Medline]
- Derbent M, Saygili A, Tokel K, Baltaci V. Pulmonary artery sling in a case of trisomy 18 Am J Med Genet 2001;101:184-185.[Medline]
- Loureiro M, Moreira J, Vaz T, Ribeiro A, Monterroso J, Areias JC. Anomalous origin of the left pulmonary artery sling: a case report and review of the literature Revista Portuguesa de Cardiologia 1998;17:811-815.[Medline]
- Regnier CH, Masson R, Kedinger V, et al. Impaired neural tube closure, axial skeleton malformations, and tracheal ring disruption in TRAF4-deficient mice Proc Natl Acad Sci 2002;99:5585-5590.[Abstract/Free Full Text]
- Alescio T, Cassini A. Induction in vitro of tracheal buds by pulmonary mesenchyma grafted on tracheal epithelium J Exp Zool 1962;150:83-94.[Medline]
- O’Sullivan BP, Frassica JJ, Rayder SM. Tracheal bronchus: a cause of prolonged atelectasis in intubated children Chest 1998;113:537-540.[Medline]
- Stenmark KR, Gebb SA. Lung vascular development: breathing new life into an old problem Am J Respir Cell Mol Biol 2003;28:133-137.[Free Full Text]
- Clements BS, Warner J. Pulmonary sequestration and related congenital bronchopulmonary-vasculture malformations: nomenclature and classification based on anatomical and embryological considerations Thorax 1987;42:401-408.[Abstract/Free Full Text]
- Lee ML, Tsao LY, Chaou WT, et al. Revisit on congenital bronchopulmonary vascular malformations: a haphazard branching theory of malinosculations and its clinical classification and implication Pediatr Pulmonol 2002;33:1-11.[Medline]
- Dunham ME, Holinger LD, Becker CL, Mavroudis C. Management of severe congenital tracheal stenosis Ann Otol Rhinol Laryngol 1994;103:351-356.[Medline]
- Ziemer G, Heinemann M, Kaulitz R, Freihorst J, Seidenberg J, Wiken M. Pulmonary artery sling with tracheal stenosis: primary one-stage repair in infancy Ann Thorac Surg 1992;54:971-973.[Abstract]
- Sailer R, Zimmermann T, Bowing B, Scharf J, Zeilinger G, Stehr K. Pulmonary artery sling associated with tracheobronchial malformations Arch Otolaryngol 1992;118:864-867.[Abstract/Free Full Text]
- McLaughlin FJ, Strieder DJ, Harris GB, Vawter GP, Eraklis AJ. Tracheal bronchus: association with respiratory morbidity in childhood J Pediatr 1985;106:751-755.[Medline]
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Abstract
Introduction
