Aorticopulmonary Septum Research Articles

Early results of transcatheter electrosurgical aortic septotomy for endovascular repair of chronic dissecting aortoiliac aneurysms

ObjectiveEndovascular repair of chronic dissecting aortoiliac aneurysms is challenging given the rigid septum, compressed true lumen (TL), and target vessels frequently originating in the false lumen. We have used transcatheter electrosurgical aortic septotomy (TEAS) before stent graft implantation under intravascular ultrasound (IVUS) and fusion guidance. The purpose of this study is to assess the outcomes of TEAS during complex endovascular repair of dissecting aneurysms. MethodsFrom 2021 to 2023, 17 patients underwent TEAS. The primary end point was technical success, with secondary end points of proximal and distal seals, target vessel instability, aortic and iliac TL and cross-sectional area (CSA) expansion, and aortic-related death. During the procedure, the aortic septum is crossed through a pre-existing entry or via electrocautery-activated 0.018-in. Astato XS20 wire (Asahi-Intecc) under IVUS and fusion guidance. The penetrated wire is then snared in the false lumen and pulled through the ipsilateral femoral access. A 1-cm length of the middle of the Astato wire coating is kinked in a three-sided polygonal configuration, denuded the inner surface of the wire using a no. 15 blade, and positioned at the apex of the septum. Both ends of the Astato wire are insulated with 0.018-in. microcatheters, and the back end of the wire is denuded and connected to cautery. Gentle traction is applied to the wire, and short bursts of electrocautery cutting are applied at 60 to 80 W. ResultsThe technical success of the septotomy was 100%. No incidence of visceral or lower extremity malperfusion, vascular injury, or distal embolization occurred. Of the 17 patients, 4 underwent thoracic endovascular aneurysm repair, 2 underwent endovascular aortic repair, and 11 underwent fenestrated/branched endovascular aneurysm repair after septotomy. All target vessels were successfully stented. A distal landing zone seal with exclusion of the false lumen was achieved in 16 of the 17 patients (94.1%). One patient required embolization of the false lumen of the celiac artery after septotomy. The TL mean diameter and CSA of the descending thoracic aorta after septotomy was expanded by 7.01 ± 1.9 mm (relative mean diameter expansion, 42.3%; P < .0001) and 2.71 ± 0.4 cm2 (relative mean CSA expansion, 57.3%, P<.0001). For patients who required septotomy through the common iliac arteries, the mean TL was expanded by 8.1 ± 3.7 mm (relative mean diameter expansion, 76%; P < .0001) and 1.76 ± 0.91 cm2 (relative mean CSA expansion, 209%; P < .0001). The 1-year freedom from target vessel instability was 91%. ConclusionsThe use of IVUS and fusion-guided TEAS offers a promising technique to facilitate TL expansion and false lumen exclusion in chronic dissecting aortic aneurysms before repair. The durability and long-term outcomes of this technique in a larger cohort remain to be elucidated.

In situ laser fenestration of aortic septum to bridge false and true lumen during endovascular repair of aortic dissection

Fenestration of the septum between the true and false lumen might be necessary after aortic dissection. We report the technical aspects of in situ laser fenestration of the aortic dissection septum. Two illustrative cases are provided: a 56-year-old man with false lumen deployment of a frozen elephant trunk graft, and a 67-year-old man who underwent fenestrated endovascular aortic repair with a target branch vessel off the false lumen. In both cases, the septum was crossed using in situ laser fenestration. This technique is a precise option to enable passage between true and false lumens during endovascular repair of an aortic dissection.

Reply from authors: Adjunctive endovascular options for chronic type B aortic dissection.

Thoracic endovascular aortic repair (TEVAR) has been increasingly offered in patients with chronic type B aortic dissection (cTBAD). However, the most notable obstacle to achieving positive aortic remodeling is the presence of a thick aortic septum, which prevents elimination of the false lumen flow despite entry tear coverage. Therefore, the absolute benefit of TEVAR remains undefined. Historically, efforts have been devoted to endovascularly eliminating residual false lumen flow, primarily focusing on 2 approaches: one is obliteration of the false lumen using embolization techniques, and the other is creation of a single aortic lumen as optimized landing zones.

Midterm Clinical Outcomes of Retrograde Open Mesenteric Stenting for Mesenteric Ischemia

Retrograde open mesenteric stenting (ROMS) has become a mainstay in treatment of mesenteric ischemia; however, follow-up in contemporary studies is limited. A single-center retrospective review of patients undergoing ROMS from 2007 to 2020 was conducted. Demographics, presentation, and procedural details were reviewed. End points were morbidity and mortality, technical success, primary patency, reinterventions, and freedom from clinical recurrence. ROMS was performed in 34 patients, 19 female (56%). Mean age was 71±10years. Eighteen patients (53%) presented with acute mesenteric ischemia (AMI), 11 (32%) with acute-on-chronic, and 5 (15%) with chronic mesenteric ischemia. Etiology was chronic atherosclerosis with/without in-situ thrombosis in 28 patients (82%), superior mesenteric artery dissection in 3, and 1 each with embolic, vasculitic, and nonocclusive ischemia. Four patients (12%) had prior mesenteric procedures (3 Celiac/1 superior mesenteric artery stent) and 1 had unsuccessful transbrachial stenting attempt. Technical success, defined as successful stenting through a retrograde approach was attained in 31 patients (91%), with the 3 remaining patients treated with transbrachial stenting in 2 and iliomesenteric bypass in 1. Covered stents were used in 21 patients (64%) with or without stent extension with bare-metal stents. Eight patients (23%) required thromboembolectomy and 9 (26%) underwent patch angioplasty. Thirty-day mortality rate was 35%, all in patients with AMI (10) or acute-on-chronic (2). Eighteen patients (53%) underwent bowel resection, all presenting acutely. Early reinterventions within the first 30days were required in 5 patients (15%), including 2 redo ROMS with thrombectomy and endarterectomy, 2 percutaneous stent extensions, and 1 aortic septum fenestration with coiling of a jejunal branch pseudoaneurysm. With a median follow-up of 3.7 (interquartile range: 0.8-5.0) years, in patients surviving discharge, 5 required reintervention yielding freedom from reintervention rates of 87% at 1year and 71% at 3years. All postdischarge reinterventions were endovascular with no conversion to bypass. The overall 1-year and 3-year primary patency rates were 70% and 61% (primary-assisted patency at 1 and 3years was 87% and secondary patency at 1 and 3years was 97%). The freedom from symptom recurrence was 95% at 1 and 3years. ROMS carries high rates of technical success in patients with mesenteric ischemia, despite a high chronic atherosclerotic burden. Although mid-term patency rates are acceptable, AMI is still associated with high early morbidity and mortality, with high rates of associated bowel resection. ROMS is a valuable tool in the armamentarium of vascular surgeons.

Midterm Clinical Outcomes Of Retrograde Open Mesenteric Stenting For Mesenteric Ischemia

<h3>INTRODUCTION AND OBJECTIVES</h3> Retrograde open mesenteric stenting (ROMS) has become a mainstay in treatment of mesenteric ischemia, however, follow-up in contemporary studies is limited. <h3>METHODS</h3> Single-center retrospective review of patients undergoing ROMS from 2007-2020 was conducted. Demographics, presentation, procedural details were reviewed. Endpoints were morbidity and mortality, technical success, primary patency, reinterventions, and freedom from clinical recurrence. <h3>RESULTS</h3> ROMS was performed in 34 patients, 19 female (56%). Mean age was 71±10 years. Eighteen patients (53%) presented with acute mesenteric ischemia (AMI), eleven (32%) with acute-on-chronic (ACMI), and five (15%) with chronic mesenteric ischemia (CMI). Etiology was chronic atherosclerosis with/without in-situ thrombosis in 28 patients (82%), SMA dissection in three, and one each with embolic, vasculitic, and non-occlusive ischemia. Four patients (12%) had prior mesenteric procedures (3 Celiac/1 SMA stent) and one had unsuccessful transbrachial stenting attempt. Technical success, defined as successful stenting through retrograde approach was 91%; three remaining patients were treated with transbrachial stenting in two patients and iliomesenteric bypass in one. Covered stents were utilized in 21 patients(64%). Eight patients(23%) required thromboembolectomy and nine(26%) underwent patch angioplasty. Thirty-day mortality rate was 35%, all in patients with AMI (10) or ACMI (2). Eighteen patients (53%) underwent bowel resection, all presenting acutely. Early reinterventions were required in 5 patients (15%); two redo ROMS with thrombectomy and endarterectomy, two percutaneous stent extensions, one aortic septum fenestration. At a median follow-up of 3.7(0.1-8.4) years, cumulative reintervention rate was 24% (8 patients, all four late reinterventions were endovascular with no conversion to bypass), primary patency was 73%(primary-assisted patency 91%, secondary patency 97%), and freedom from clinical recurrence was 95%. <h3>CONCLUSIONS</h3> ROMS carries high rates of technical success in patients with mesenteric ischemia, despite high chronic atherosclerotic burden. While mid-term patency rates are acceptable, early mortality and bowel resection remain common in acute presentations.

Descrições clínicas e anatomopatológicas de cão com hemitruncus arterioso: relato de caso

ABSTRACT The anomalous origin of the pulmonary trunk in the ascending aorta, defined as arterious hemitruncus, is a rare congenital malformation in dogs, caused by a defect in the spiral septum. Thus, given the unusual occurrence in the canine species, the systemic severity and the high lethality, the aim of this study was to describe this heart disease in a three-month-old male German Spitz puppy, emphasizing clinical changes of the necropsy and microscopics. The animal had cyanosis, dyspnea and weakness and was forwarded for necropsy after sudden death. Numerous changes were detected in the post-mortem examination, including in the heart, as cardiomegaly and absence of the arterial ligament, which was replaced by the complete fusion between the ascending aorta and the pulmonary trunk, after leaving both the left and right ventricles, respectively and, among the microscopic findings, cardiomyocyte hypertrophy stood out. The association of these findings with the history indicated the diagnosis of arterious hemitruncus followed by cardiorespiratory failure, emphasizing the importance of out complementary cardiological exams in young symptomatic patients for the survival of those affected. Arterious hemitruncus, although rare, must be added in the differential diagnosis of other heart diseases that cause similar clinical signs.

Over-expression of Fgf8 in cardiac neural crest cells leads to persistent truncus arteriosus.

During cardiogenesis, the outflow tract undergoes a complicated morphogenesis, including the re-alignment of the great blood vessels, and the separation of aorta and pulmonary trunk. The deficiency of FGF8 in the morphogenesis of outflow tract has been well studied, however, the effect of over-dosed FGF8 on the development of outflow tract remains unknown. In this study, Rosa26R-Fgf8 knock-in allele was constitutively activated by Wnt1-cre transgene in the mouse neural crest cells presumptive for the endocardial cushion of outflow tract. Surprisingly, Wnt1-cre; Rosa26R-Fgf8 mouse embryos exhibited persistent truncus arteriosus and died prior to E15.5. The cardiac neural crest cells in Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus did not degenerate as in WT controls, but proliferated into a thickened endocardial cushion and then, blocked the blood outflow from cardiac chambers into the lungs, which resulted in the embryonic lethality. Although the spiral aorticopulmonary septum failed to form, the differentiaion of the endothelium and smooth muscle in the Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus were impacted little. However, lineage tracing assay showed that the neural crest derived cells aggregated in the cushion layer, but failed to differentiate into the endothelium of Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus. Further investigation displayed the reduced p-Akt and p-Erk immunostaining, and the decreased Bmp2 and Bmp4 transcription in the endothelium of Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus. Our findings suggested that Fgf8 over-expression in cardiac neural crest impaired the formation of aorticopulmonary septum by suppressing the endothelial differentiation and stimulating the proliferation of endocardial cushion cells, which implicated a novel etiology of persistent truncus arteriosus.

Laser aortic septotomy during thoracic endovascular aortic repair for chronic type B aortic dissection.

Persistent false lumen perfusion due to the presence of a thick aortic septum is a significant obstacle to successful thoracic endovascular aortic repair for chronic type B aortic dissection (cTBAD). We describe our new approach of laser aortic septotomy to optimize the landing zone. Between 2019 and 2020, 11 patients with cTBAD with degenerative aneurysm underwent laser aortic septotomy during thoracic endovascular aortic repair. A prospectively maintained database was retrospectively reviewed. The median age was 70.0years, and 10 (91%) were men. Six (55%) were de novo type B aortic dissection and 5 (45%) were residual type B aortic dissection. The age of aortic dissection was 2.9years (interquartile range, 1.1-12.1). Technical success was achieved in 91% (10/11). In 1 case (9%), laser aortic septotomy was not feasible due to extremely tortuous aorta. Among successful cases, the median extents of proximal and distal laser fenestrations were Th7.5 and Th11.0, respectively and distal landing zones included zone 4 (40%) and zone 5 (60%). Two (18%) underwent a continuous longitudinal laser fenestration, and 8 (73%) had longitudinal spot laser fenestrations with immediate balloon dilatations. Apposition of the stent-graft to the outer aortic wall of the newly created common aortic lumen with elimination of retrograde false lumen flow was achieved in all cases. This is the first description using the laser technology to optimize the distal landing zone for cTBAD. This new technique is safe and reproducible, with excellent controllability to achieve aortic septotomy at the desired target aorta segment.

Conditional inactivation of Foxc1 and Foxc2 in neural crest cells leads to cardiac abnormalities

Cardiac neural crest cells (cNCCs) are required for normal heart development. cNCCs are a multipotent and migratory cell lineage that differentiates into multiple cell types. cNCCs migrate into the developing heart to contribute to the septation of the cardiac outflow tract (OFT). Foxc1 and Foxc2 are closely related members of the FOX (Forkhead box) transcription factor family and are expressed in cNCC during heart development. However, the precise role of Foxc1 and Foxc2 in cNCCs has yet to be fully described. We found that compound NCC-specific Foxc1;Foxc2 mutant embryos exhibited persistent truncus arteriosus (PTA), ventricular septal defects (VSDs), and thinning of the ventricular myocardium. Loss of Foxc1/c2 expression in cNCCs resulted in abnormal patterns of cNCC migration into the OFT without the formation of the aorticopulmonary septum. Further, loss of Foxc1 expression in cNCCs resulted in normal OFT development but abnormal ventricular septal formation. In contrast, loss of Foxc2 expression in NCCs led to no obvious cardiac abnormalities. Together, we provide evidence that Foxc1 and Foxc2 in cNCCs are cooperatively required for proper cNCC migration, the formation of the OFT septation, and the development of the ventricles. Our data also suggests that Foxc1 expression may play a larger role in ventricular development compared to Foxc2.

Knowing Real Cardiac Anatomy Enhances Understanding of Cardiac Development

New ideas about cardiac chamber formation, interatrial septum formation and development of the outflow region can be better understood by knowing real cardiac anatomy. The definitive chambers of the heart can be regionalized into components that provide a basis for understanding their formation during prenatal embryonic development. Each atrium has a venous inlet, a body, an appendage and a vestibule, while each ventricle consists of an inlet, an apical trabeculated portion and an outlet. During development several precursors combine to form the components of definitive chambers. Recent studies have challenged the classical version of interatrial septum formation, particularly the presence of a secondary atrial septum (septum secundum), and the closure of the primary atrial foramen (ostium primum). These studies suggest that the primary atrial septum (septum primum) merges with a fold of myocardium from the roof of the right atrium rather than with a second septum. This fold can be demonstrated in the dissection laboratory. Closure of the primary atrial foramen is accomplished by fusion of the ingrowing vestibular spine fusing with the mesenchymal cap of the primary septum and the merged AV endocardial cushions. This forms the anterior inferior atrial buttress that might be considered a secondary atrial septum. Finally, formation of the outflow region can be better understood using a tripartite explanation rather that the traditional bipartite version. During cardiac looping, the outflow region elongates and develops a bend in the middle. This flexure can define the outflow region into proximal, intermediate and distal segments. From these segments the outflow regions of the ventricles, the aortic valves and the intrapericardial roots of the great vessels are formed. The septum dividing the proximal segment is formed exclusively from endocardial cushion tissue, while the septum that partitions the intermediate and distal outflow regions is derived from cushion tissue and neural crest ectomesenchyme. Traditionally the aorticopulmonary septum was described as partitioning the entire outflow region. More recent examination of outflow tract development suggests that the aorticopulmonary septum only partitions the distal portion of the outflow region and the aortic sac. The intrapericardial and extrapericardial roots of the great vessels form from the division of the distal outflow region and the aortic sac.

Emergency use of Physician-modified Fenestrated Endograft in a Symptomatic Patient Who was Waiting for a Manufactured Graft to Treat Chronic Post-dissection Thoracoabdominal Aneurysm

Introduction - Fenestrated-branched endovascular repair (F-BEVAR) using custom manufactured devices (CMDs) has been applied to treat post-dissection thoracoabdominal aortic aneurysms (TAAA), but the long wait period for device manufacturing limits its application in patients with symptomatic or contained ruptured aneurysms. Methods - A 59-year-old female patient who was waiting for CMD (Cook Medical, Brisbane, Australia) presented with a symptomatic post-dissection TAAA. The patient had undergone a successful first stage thoracic endovascular repair with creation of a fenestration in the distal aortic septum to perfuse the right kidney, which originated from the false lumen. Repeat computed tomography angiography revealed compression of the true lumen below the level of the fenestration with pressurization of the false lumen (Figure A). The patient was treated emergently using a physician-modified endovascular graft (PMEG) with four fenestrations and preloaded guidewires. The technique of PMEG using low-profile Zenith Alpha™ Thoracic stent graft (Cook Medical, Copenhagen Denmark) is presented with video and illustrations. Results - The thoracic stent-graft was modified onsite under strict sterile technique using the same measurements obtained for the original CMD request. The active fixation bards were removed to facilitate re-sheathing. Four fenestrations were created with ophthalmologic cautery and reinforced using a double layer of nitinol wire (Figure B). Radiopaque markers were added for orientation. Four 0.014-inch preloaded guidewires were added exiting via the top of the delivery system (Figure C). Diameter-reducing sutures were applied and the device was reintroduced into the original 18Fr sheath. Using bilateral femoral and right brachial approach, a long 5Fr sheath was introduced via the brachial approach exiting via the femoral approach. The PMEG was loaded into a through-and-through wire, while the four preloaded guidewires were loaded into a long 5Fr brachial sheath. The device and sheath were advanced into position and deployed in a stepwise fashion allowing sequential catheterization of the celiac axis, superior mesenteric artery and both renal arteries in the compressed true lumen (Figure D). Once all vessels were catheterized, the bifurcated device and iliac limbs were added and flow was restored to the lower extremities. Sequential renal-mesenteric stenting was done. A completion cone beam computed tomography revealed successful aneurysm exclusion. The repair was completed with a total endovascular time of 133 minutes and the patient was dismissed on postoperative day 10. Follow-up CTA showed patent stent-graft with type 2 endoleak. A total of 6 PMEG repairs with low profile Zenith Alpha™ Thoracic stent grafts were performed at our institution between 2016 and 2018, representing 2% of the 280 patients treated by F-BEVAR during this period. All six patients who had PMEGs did not meet inclusion criteria for an ongoing prospective study using CMDs Conclusion - PMEGs remain a valuable option to treat TAAAs, including chronic post-dissection aneurysms, in patients with symptoms or contained rupture who are not ideally suited for off-the-shelf devices. Compared to tighter stainless-steel Z stents, the widely spaced nitinol stents of the Zenith Alpha™ Thoracic endograft offer more space for fenestration placement.

Cardiac neural crest contributes to cardiomyocytes in amniotes and heart regeneration in zebrafish.

Cardiac neural crest cells contribute to important portions of the cardiovascular system including the aorticopulmonary septum and cardiac ganglion. Using replication incompetent avian retroviruses for precise high-resolution lineage analysis, we uncover a previously undescribed neural crest contribution to cardiomyocytes of the ventricles in Gallus gallus, supported by Wnt1-Cre lineage analysis in Mus musculus. To test the intriguing possibility that neural crest cells contribute to heart repair, we examined Danio rerio adult heart regeneration in the neural crest transgenic line, Tg(-4.9sox10:eGFP). Whereas the adult heart has few sox10+ cells in the apex, sox10 and other neural crest regulatory network genes are upregulated in the regenerating myocardium after resection. The results suggest that neural crest cells contribute to many cardiovascular structures including cardiomyocytes across vertebrates and to the regenerating heart of teleost fish. Thus, understanding molecular mechanisms that control the normal development of the neural crest into cardiomyocytes and reactivation of the neural crest program upon regeneration may open potential therapeutic approaches to repair heart damage in amniotes.

Fluid dynamics and forces in the HH25 avian embryonic outflow tract.

The embryonic outflow tract (OFT) eventually undergoes aorticopulmonary septation to form the aorta and pulmonary artery, and it is hypothesized that blood flow mechanical forces guide this process. We performed detailed studies of the geometry, wall motions, and fluid dynamics of the HH25 chick embryonic OFT just before septation, using noninvasive 4D high-frequency ultrasound and computational flow simulations. The OFT exhibited expansion and contraction waves propagating from proximal to distal end, with periods of luminal collapse at locations of the two endocardial cushions. This, combined with periods of reversed flow, resulted in the OFT cushions experiencing wall shear stresses (WSS or flow drag forces) with elevated oscillatory characteristics, which could be important to signal for further development of cushions into valves and septum. Furthermore, the OFT exhibits interesting double-helical flow during systole, where a pair of helical flow structures twisted about each other from the proximal to distal end. This coincided with the location of the future aorticopulmonary septum, which also twisted from the proximal to distal end, suggesting that this flow pattern may be guiding OFT septation.

Foxc2 is required for proper cardiac neural crest cell migration, outflow tract septation, and ventricle expansion.

Proper development of the great vessels of the heart and septation of the cardiac outflow tract requires cardiac neural crest cells. These cells give rise to the parasympathetic cardiac ganglia, the smooth muscle layer of the great vessels, some cardiomyocytes, and the conotruncal cushions and aorticopulmonary septum of the outflow tract. Ablation of cardiac neural crest cells results in defective patterning of each of these structures. Previous studies have shown that targeted deletion of the forkhead transcription factor C2 (Foxc2), results in cardiac phenotypes similar to that derived from cardiac neural crest cell ablation. We report that Foxc2-/- embryos on the 129s6/SvEv inbred genetic background display persistent truncus arteriosus and hypoplastic ventricles before embryonic lethality. Foxc2 loss-of-function resulted in perturbed cardiac neural crest cell migration and their reduced contribution to the outflow tract as evidenced by lineage tracing analyses together with perturbed expression of the neural crest cell markers Sox10 and Crabp1. Foxc2 loss-of-function also resulted in alterations in PlexinD1, Twist1, PECAM1, and Hand1/2 expression in association with vascular and ventricular defects. Our data indicate Foxc2 is required for proper migration of cardiac neural crest cells, septation of the outflow tract, and development of the ventricles. Developmental Dynamics 247:1286-1296, 2018. © 2018 Wiley Periodicals, Inc.

Konno Operation: The 2015 Kyoto Symposium Konno Memorial Lecture.

The Konno operation consists of a prosthetic aortic valve replacement by using an anterior enlargement of the small aortic annulus. The original procedure includes a longitudinal incision in the aortic septum placed near the midpoint between the two coronary ostia, a vertical incision in the outflow tract of the right ventricle to join the septal incision, prosthetic aortic valve replacement, and patch reconstruction of the outflow tracts of both ventricles by means of a fusiform Dacron patch. The concept of this operation has been applied in other complex operations, such as modified Konno operation, Ross-Konno operation, and aortic valve replacement after arterial switch operation.

AcvR1-mediated BMP signaling in second heart field is required for arterial pole development: Implications for myocardial differentiation and regional identity

BMP signaling plays an essential role in second heart field-derived heart and arterial trunk development, including myocardial differentiation, right ventricular growth, and interventricular, outflow tract and aortico-pulmonary septation. It is mediated by a number of different BMP ligands, and receptors, many of which are present simultaneously. The mechanisms by which they regulate morphogenetic events and degree of redundancy amongst them have still to be elucidated. We therefore assessed the role of BMP Type I receptor AcvR1 in anterior second heart field-derived cell development, and compared it with that of BmpR1a.By removing Acvr1 using the driver Mef2c[AHF]-Cre, we show that AcvR1 plays an essential role in arterial pole morphogenesis, identifying defects in outflow tract wall and cushion morphology that preceded a spectrum of septation defects from double outlet right ventricle to common arterial trunk in mutants. Its absence caused dysregulation in gene expression important for myocardial differentiation (Isl1, Fgf8) and regional identity (Tbx2, Tbx3, Tbx20, Tgfb2). Although these defects resemble to some degree those in the equivalent Bmpr1a mutant, a novel gene knock-in model in which Bmpr1a was expressed in the Acvr1 locus only partially restored septation in Acvr1 mutants. These data show that both BmpR1a and AcvR1 are needed for normal heart development, in which they play some non-redundant roles, and refine our understanding of the genetic and morphogenetic processes underlying Bmp-mediated heart development important in human congenital heart disease.

Aorta and pulmonary trunk - comparison of wall structure in typical and atypical (Ross procedure) blood pressure conditions

The ascending aorta and pulmonary trunk develop from the common truncus arteriosus that later becomes symmetrically divided by the aorticopulmonary septum. Normally, the systolic pressure value and the diastolic pressure gradient in the aorta is much higher than that in the pulmonary artery. In the Ross procedure, patient’s diseased aortic valve is replaced with their own pulmonary valve and as a consequence the pulmonary trunk is placed in the aortic root position. Typically, a reinforcement of transposed pulmonary trunk is necessary to avoid vessel dilation. In order to investigate how the blood flow characteristics determine the vessel wall structure we examined by immunochemistry the wall of normal aorta (NA), normal pulmonary trunk (NPT), transposed pulmonary trunk (trPT) and transposed pulmonary trunk with reinforcement (trPT-R). Throughout the tunica media of NA, elastic fibers form numerous, conspicuous and orderly arranged wavy lamellae that parallel thin layers of smooth muscle cells between the internal and external elastic membrane. In the NPT, smooth muscle cells run amid collagen fibers and form layers that are thicker and irregular, with elastic fibers arranged accordingly. In the trPT, intima denudation and media disruptions were observed. In the tunica media, smooth muscle cells were abundant, but muscle fibers, with irregular profiles and no discernible alignment, were widely spaced with intervening collagen fibers. In the trPA-R, the endothelial lining was preserved and elastic fibers formed a thick and highly organized layer of concentric lamellae in the middle third of tunica media. The structure of normal aorta and pulmonary trunk, both elastic arteries, with common embryological origin, differs significantly in terms of smooth muscle and elastic sheets number and organization. The animal model of Ross procedure with pulmonary trunk in aorta position further underscores the role of blood pressure and mechanical stress in vessel wall modification.

Digestive system anatomy of the Acipenser persicus: New features

Sturgeon is one of the most important species of the Caspian Sea aquatics. Unfortunately, this species faces the threat of extinction today. This makes specific studies on any type of sturgeons more important than before. Studies like histological studies, radiology, and sonography, all require a complete understanding of the anatomy of this fish. Since pilot studies showed some misconceptions in description of the sturgeon digestive system, this study was conducted to evaluate more precise anatomical structure of the digestive system of Acipenser persicus as the most important sturgeon species of Iran. A total of 40 adult Acipenser persicus were used in this experiment. They were autopsied primary to the study. All parts of the digestive system from buccal cavity toward rectum and anal orifice were evaluated. The anatomical structure and relations of the different parts of the digestive system including oral cavity, pharynx, esophagus, glandular stomach, muscular stomach, pyloric process, small intestine, spiral intestine, rectum, liver and pancreas were described. The digestive tube is relatively short. The stomach has two parts. The first part, or the proventricle, is U-shaped. The second part or gizzard has thick muscles and is almost surrounded with liver lobes. Pyloric caecum is located on the left side bottom of the gizzard as a sponge like structure. The intestines are made of 3 parts: the small intestine, the spiral colon, and the rectum. The small intestine has two flexures that separate it to three parts named the descending, ascending, and the end part, respectively. The spiral colon is the longest part of the digestive tube. This part has mucosal spiral septum on the inner surface. The rectum is short and located in the middle of the abdominal cavity. However, in the present study the opening was shown to be located in the muscular stomach and the intestine junction, just close to the gall bladder duct opening.

Regulated metabolism of Vitamin A by retinol dehydrogenase 10 is critical for embryonic development of the heart

Congenital heart disease is a serious human health issue, affecting as many as 1% of live births. For most cases of cardiac birth defect the cause is unknown, reflecting the limitations of our understanding of which environmental agents, genetic factors, and gene‐environment interactions contribute to cardiac abnormalities. The purpose of the current study is to investigate the mode whereby an embryo converts Vitamin A into the potent morphogen retinoic acid and to understand how disturbances in the production of retinoic acid may contribute to developmental malformations of the heart. Precise regulation of retinoic acid production is critical ‐ either excessive or insufficient levels result in cardiac birth defects ‐ yet very little is known about the mechanism whereby this process is controlled. We have demonstrated that the short chain dehydrogenase/reductase RDH10 is the primary enzyme responsible for the first step of embryonic Vitamin A metabolism. We show that embryos with mutations in Rdh10 have severe cardiac developmental abnormalities, including defects in heart looping, myocardial growth, aorticopulmonary septation and morphogenesis of the atria. Using transgenic reporter mice and RNA in situ hybridization we have determined that the Rdh10−/− cardiac phenotypes are associated with abnormal expression of Hox family A‐P patterning genes and also with defects in cell adhesion and abnormal distribution of extracellular matrix molecules. Finally, utilizing quantitative reverse transcriptase PCR we have demonstrated that Rdh10 gene transcription is a point for feedback control in regulation of retinoic acid production. These data suggest that Rdh10 may be a candidate gene for association with human cardiac abnormalities. Moreover, the data shed light on the molecular mechanism whereby disruptions in Vitamin A metabolism may contribute to congenital heart disease.Grant Funding Source: NIH‐COBRE

Focal Adhesion Kinase Regulates Smooth Muscle Cell Recruitment to the Developing Vasculature

The investment of newly formed endothelial cell tubes with differentiated smooth muscle cells (SMC) is critical for appropriate vessel formation, but the underlying mechanisms remain unknown. We previously showed that depletion of focal adhesion kinase (FAK) in the nkx2.5 expression domain led to aberrant outflow tract (OFT) morphogenesis and strove herein to determine the cell types and mechanisms involved. We crossed fak(loxp) targeted mice with available Cre drivers to deplete FAK in OFT SMC (FAK(wnt) and FAK(nk)) or coronary SMC (FAK(cSMC)). In each case, depletion of FAK led to defective vasculogenesis that was incompatible with postnatal life. Immunohistochemical analysis of the mutant vascular structures revealed that FAK was not required for progenitor cell proliferation, survival, or differentiation into SMC but was necessary for subsequent SMC recruitment to developing vasculature. Using a novel FAK-null SMC culture model, we found that depletion of FAK did not influence SMC growth or survival, but blocked directional SMC motility and invasion toward the potent endothelial-derived chemokine, platelet-derived growth factor PDGFBB. FAK depletion resulted in unstable lamellipodial protrusions due to defective spatial-temporal activation of the small GTPase, Rac-1, and lack of Rac1-dependent recruitment of cortactin (an actin stabilizing protein) to the leading edge. Moreover, FAK null SMC exhibited a significant reduction in stimulated extracellular matrix degradation. FAK drives PDGFBB-stimulated SMC chemotaxis/invasion and is essential for SMC to appropriately populate the aorticopulmonary septum and the coronary vascular plexus.