False Lumen Formation Research Articles

A Case Report of a 44-Year-Old Middle-Aged Woman with Acute Chest Pain

<p>胸痛是臨床常見的主訴，鑑別診斷必須配合心電圖，並優先考量會猝死的心血管疾病。本篇個案是一位44歲的中年女性，因急性胸痛至急診就醫，經連續追蹤心電圖與抽血檢驗，診斷為非ST節段上升之急性冠心症(non ST-elevation acute coronary syndrome, NSTE-ACS)，心導管冠狀動脈攝影檢查結果合乎自發性冠狀動脈剝離(spontaneous coronary artery dissection, SCAD)的變化。本文之目的在強調無冠狀動脈疾病危險因子的中年女性發生急性冠心症，須考慮SCAD的可能性。SCAD的病因為冠狀動脈內膜撕裂，血流進入血管內壁產生血腫，當假腔壓迫冠狀動脈血流會使心肌缺血而導致胸痛的症狀，與冠狀動脈阻塞型心肌梗塞成因不同，故治療與處理的方式有不同之處，必須視臨床病人情況做謹慎的評估，以降低侵入性治療的風險。照顧個案期間藉由最少的侵入性檢查給予正確診斷，並配合適當的藥物治療，達成緩解病人症狀、預防合併症與復發的治療目的。藉由這篇病例報告，希望醫護人員對照顧自發性冠狀動脈剝離的病人有更多的認知。</p> <p> </p><p>Chest pain is a common clinical complaint. Electrocardiograms must be included in diagnosis, and the priority should be given to cardiovascular diseases that may lead to sudden death. The case described here is a 44-year-old middle-aged woman who presented to the emergency room with unendurable chest pain. After continuous follow-up ECG and blood tests, she was diagnosed with non-ST-elevation acute coronary syndrome (NSTE-ACS). The result of coronary angiography correspond to sponta-neous coronary artery dissection (SCAD). The purpose of this article is to emphasize the possibility of SCAD in acute coronary syndrome in middle-aged women without coronary artery disease risk fac-tors. SCAD is characterized by intimal tear, intramural hematoma, and false lumen formation, which can obstruct coronary blood flow and cause myocardial ischemia with chest pain. Since the etiology of SCAD is different from obstructive coronary artery myocardial infarction, their medical treatments must be carefully evaluated through clinical patient conditions to reduce the risks of invasive proce-dure. In this case, early and correct diagnosis was made to reduce invasive procedure, and appropriate medication therapy were applyed to achieve the purpose of relieving the patient’s symptoms, prevent-ing complications and recurrence. Through this case report, it is hoped that healthcare professionals will improve awareness of caring for patients with spontaneous coronary artery dissection.</p> <p> </p>

β-Aminopropionitrile Induces Distinct Pathologies in the Ascending and Descending Thoracic Aortic Regions of Mice.

β-aminopropionitrile (BAPN) is a pharmacological inhibitor of LOX (lysyl oxidase) and LOXLs (LOX-like proteins). Administration of BAPN promotes aortopathies, although there is a paucity of data on experimental conditions to generate pathology. The objective of this study was to define experimental parameters and determine whether equivalent or variable aortopathies were generated throughout the aortic tree during BAPN administration in mice. BAPN was administered in drinking water for a period ranging from 1 to 12 weeks. The impacts of BAPN were first assessed with regard to BAPN dose, and mouse strain, age, and sex. BAPN-induced aortic pathological characterization was conducted using histology and immunostaining. To investigate the mechanistic basis of regional heterogeneity, the ascending and descending thoracic aortas were harvested after 1 week of BAPN administration before the appearance of overt pathology. BAPN-induced aortic rupture predominantly occurred or originated in the descending thoracic aorta in young C57BL/6J or N mice. No apparent differences were found between male and female mice. For mice surviving 12 weeks of BAPN administration, profound dilatation was consistently observed in the ascending region, while there were more heterogeneous changes in the descending thoracic region. Pathological features were distinct between the ascending and descending thoracic regions. Aortic pathology in the ascending region was characterized by luminal dilatation and elastic fiber disruption throughout the media. The descending thoracic region frequently had dissections with false lumen formation, collagen deposition, and remodeling of the wall surrounding the false lumen. Cells surrounding the false lumen were predominantly positive for α-SMA (α-smooth muscle actin). One week of BAPN administration compromised contractile properties in both regions equivalently, and RNA sequencing did not show obvious differences between the 2 aortic regions in smooth muscle cell markers, cell proliferation markers, and extracellular components. BAPN-induced pathologies show distinct, heterogeneous features within and between ascending and descending aortic regions in mice.

Oxidative stress drives vascular smooth muscle cell damage in acute Stanford type A aortic dissection through HIF-1α/HO-1 mediated ferroptosis

BackgroundAcute Stanford type A aortic dissection (ATAAD) is characterized by intimal tearing and false lumen formation containing large amounts of erythrocytes with heme. Heme oxygenase 1 (HO-1) is the key enzyme to degrade heme for iron accumulation and further ferroptosis. The current study aimed at investigating the role of HO-1 in the dissection progression of ATAAD. MethodsBioinformatic analyses and experimental validation were performed to reveal ferroptosis and HO-1 expression in ATAAD. Human aortic vascular smooth muscle cell (HA-VSMC) was used to explore underlying molecular mechanisms and the role of HO-1 overexpression in ATAAD. ResultsFerroptosis was identified as a critical manner of regulated cell death in ATAAD. HO-1 was screened as a key signature of ferroptosis in ATAAD, which was closely associated with oxidative stress. Single cell/nucleus transcriptomic analysis and histological staining revealed that HO-1 and HIF-1α were upregulated in vascular smooth muscle cell (VSMC) of ATAAD. Further in vitro experiments showed that H2O2-induced oxidative stress increased VSMC ferroptosis with the overexpression of HO-1, which could be suppressed by HIF-1α inhibitor PX-478. HIF-1α could transcriptionally regulate the expression of HO-1 through binding to its promoter region. Pharmacological inhibition of HO-1 by zinc protoporphyrin (ZnPP) did not reduce H2O2-induced HA-VSMC damage without heme co-incubation. However, H2O2-induced HA-VSMC damage was worsened when heme was added into the medium, and ZnPP could reduce HA-VSMC damage in this condition. ConclusionHO-1 is a key signature of VSMC ferroptosis in ATAAD. HIF-1α/HO-1 mediated ferroptosis might participate in oxidative stress induced VSMC damage.

Abstract 13284: New Elastic Fiber Formation by Non-Smooth Muscle Lineage Cells During the Progression of Aortic Dissections

Introduction: Aortic dissection (AD) is a life-threatening vascular disease displaying the disruption of the extracellular matrix (ECM). Elastic fibers are a major component of ECM and confer structural integrity to the aortic wall. Normally, elastic fibers are minimally synthesized in adulthood. However, it remains unknown whether and how elastic fibers are synthesized following ADs. Methods and Results: AD was induced by administration of β-aminopropionitrile (BAPN, 0.5% wt/vol) to male C57BL/6J mice at 4 weeks of age. Thoracic aortas were collected after 4 or 12 weeks of BAPN administration. False lumen formation with fresh hematomas was observed at 4 weeks of BAPN administration, indicating development of acute ADs. The false lumen developed striking remodeling at 12 weeks, suggesting progression to the chronic phase. RT-qPCR revealed that mRNA abundance of tropoelastin, a precursor of elastic fibers, was increased significantly at the chronic phase of ADs, but not at the acute phase. Tropoelastin mRNA was observed primarily in the vascular wall of the false lumen, as evidenced by in situ hybridization. Of interest, elastic fibers were formed in the wall of the false lumen in chronic ADs. These data suggest that elastic fibers were newly synthesized during the progression of ADs. Immunostaining revealed that the walls of true and false lumens of chronic ADs were mainly composed of cells expressing both αSMA (encoding by Acta2 ) and MYH11, common markers for smooth muscle cells (SMCs). However, in a lineage tracing study, the walls of the false lumen of chronic ADs were negative for the Acta2 lineage, suggesting that cells in the wall of the false lumen were derived from a non-SMC lineage but acquired SMC properties during AD progression. Bulk RNA sequencing identified the increased abundance of 2,799 genes in chronic ADs and 102 transcription factors were predicted to regulate these genes. Among them, JunB was the most abundant molecule that can be aligned in the promotor region of tropoelastin. Of note, JunB was expressed adjacent to both αSMA-positive cells and new elastic fibers in the dissected aortas. Conclusion: ADs exhibit vascular remodeling with newly elastic fiber formation by non-SMC lineage cells during the disease progression.

Endovascular treatment of the dissected proximal aortic arch: a systematic review.

Surgical repair of aortic dissection involving the proximal aortic arch is associated with higher morbidity and mortality, in particular when elderly high-risk patients are concerned. Endovascular treatments for this disease are under evaluation and some reports exist. We investigated the current use of catheter-based treatments for the dissected proximal aortic arch repair. We searched in PubMed and MEDLINE databases up to the end of June 2020 for studies on endovascular treatment of the dissected proximal aortic arch. Data on demographic, procedure and stent graft (SG) details, access route, mortality with cause of death, complications and follow-up were extracted. A systematic review on the employed technology, procedure and outcome was performed. A total number of 15 articles (13 retrospective reports and 2 case reports) were deemed eligible and were included in the study. In total, 140 patients (mean age: 56.7 years in 106 cases) received endovascular treatments for the dissected proximal aortic arch (unspecific aortic dissection: 14; acute and subacute type A aortic dissection: 88; chronic type A aortic dissection: 23; type B aortic dissection with retrograde type A dissection: 15). The procedure strategy included unspecific thoracic endovascular aorta repair (TEVAR) (n = 8), TEVAR + supra-aortic debranching (n = 2), TEVAR + cervical bypass (n = 8), TEVAR + periscope SG (n = 12), TEVAR + chimney graft (n = 8), TEVAR + branched SG (n = 21) and TEVAR + fenestration (n = 81). Procedural success rate was 95.6% for 116 reported cases. Complications included endoleaks (postoperative: 2; late: 5), stroke (n = 4), late SG-induced new entry (n = 3) and new false lumen formation (n = 1). Hospital mortality was 5% (6 cases) in 13 reports (120 patients). The mean follow-up time was 26.2 ± 29.4 months and 2 patients died during follow-up. As an alternative to surgery for high-risk patients with a dissected proximal aortic arch, the endovascular treatment seems to be promising in highly selected cases. Further studies with long-term results and specifically designed devices are required to standardize this approach.

Management of endovascular treatment in spontaneous iliac artery dissections: Applications enabling classical surgery.

Background This study aims to investigate the effectiveness of endovascular applications for the treatment of spontaneous iliac artery dissections. Methods The medical records of 13 patients (12 males, 1 female; mean age 67.9±5.7 years; range, 58 to 75 years) with spontaneous iliac artery dissection between January 2017 and December 2019 were retrospectively reviewed. The diagnosis of spontaneous iliac artery dissection was made based on contrast-enhanced computed tomography. Demographic and clinical characteristics of the patients, physical examination and imaging findings, and hybrid treatments applied during endovascular treatment were analyzed. Results The mean follow-up was 12.5±1.1 (range, 6 to 16) months. Five patients received hybrid treatment during endovascular treatment. The re-entry site was closed by a patch plasty over the common femoral artery in one of these patients. Embolectomy was performed in the remaining four patients for the treatment of acute ischemia of the extremities. Since no patency could be achieved in two of the patients undergoing embolectomy, a femoropopliteal bypass was performed. The technical success and primary patency rates were 100%. No new false lumen formation, intra-stent occlusion or arterial occlusion was observed during the hospital stay and follow-up. Conclusion Endovascular methods can be safely used in the treatment of spontaneous iliac artery dissections; however, hybrid treatments may be also required in selected cases. We believe that it is effective and safe to apply endovascular and hybrid treatments without preventing possible surgical treatments which may be required in the future.

Handmade fenestrated stent grafts to preserve all supra-aortic branches in thoracic endovascular aortic repair

ObjectiveTo evaluate the efficacy and safety of a zone 0 landing aortic stent graft with handmade fenestrations for the preservation of all supra-aortic branches in thoracic endovascular aortic repair (TEVAR). MethodsThis study included 13 consecutive patients who underwent TEVAR using zone 0 landing handmade fenestrated stent grafts to preserve all supra-aortic branches from July 2016 to April 2017. Technical success was defined as the resolution of the primary aortic pathology as well as the preservation of all supra-aortic branches through the accurate alignment of the fenestration. Outcomes including technical success, perioperative morbidity and mortality, requirement of secondary interventions, and graft patency were analyzed. ResultsIn this study, 11 patients presented with aortic dissection, 1 presented with thoracic aortic aneurysm with impending rupture, and 1 presented with penetrating aortic ulcer of the thoracic aorta. The technical success rate of the primary procedure was 100%. Over a mean follow-up of 20 months, secondary endovascular procedures were performed in 6 patients to resolve 3 cases of stent graft-induced new entry, 2 cases of type Ib endoleak, and 1 case of new false lumen formation. During the study period, no complication resulting from proximal landing and fenestration occurred. ConclusionsOur experience of using handmade fenestrated stent grafts revealed preliminary results of using the grafts to preserve all supra-aortic branches in TEVAR, and results demonstrated the feasibility of this technique for achieving total arch replacement endovascularly in selective patients. Further technical advancement is anticipated, and larger studies with long-term follow-up are required.

Scavenger receptor A1 attenuates aortic dissection via promoting efferocytosis in macrophages

Macrophage class A1 scavenger receptor (SR-A1) is a pattern recognition receptor with an anti-inflammatory feature in cardiovascular diseases. However, its role in acute aortic dissection (AD) is not known yet. Using an aortic dissection model in SR-A1-deficient mice and their wild type littermates, we found that SR-A1 deficiency aggravated beta-aminopropionitrile monofumarate induced thoracic aortic dilation, false lumen formation, extracellular matrix degradation, vascular inflammation and accumulation of apoptotic cells. These pathological changes were associated with an impaired macrophage efferocytosis mediated by tyrosine-protein kinase receptor Tyro3 in vitro and in vivo. SR-A1 could directly interact with Tyro3 and was required for Tyro3 phosphorylation to activate its downstream PI3K/Akt signaling pathway. Importantly, co-culture of SR-A1−/− macrophages with apoptotic Jurkat cells resulted in less devoured apoptotic cells accompanied by swelling mitochondria and damaged ATP generation, following poor IL-10 and robust TNF-α production. Deficiency of SR-A1 did not influence phagolysosome formation during the efferocytosis. Lentiviral overexpression of Tyro3 in SR-A1−/− macrophages induced restorative phagocytosis in vitro. Administration of Tyro3 agonist protein S could restore SR-A1−/− macrophages phagocytosis in vitro and in vivo. These findings suggest that SR-A1-Tyro3 axis in macrophages mitigate AD damage by promoting efferocytosis and inhibiting inflammation.

Spontaneous intramural esophageal dissection preceded by intramural esophageal hematoma: Report of a case study

Spontaneous intramural esophageal dissection (IED) is a rare disorder characterized by acute symptoms, including chest pain, odynophagia, dysphagia, or hematemesis and remarkable endoscopic or radiographic findings. The pathophysiology is complex and remains poorly understood. Here, we report a 63‐year‐old woman who presented with progressive odynophagia, dysphagia, and weight loss. We diagnosed spontaneous IED with false lumen formation extending to the stomach using ultra‐thin upper endoscopy and water‐soluble contrast esophagogram. Comparing the patient's chronological computed tomographic images before and after symptom onset, we found that spontaneous IED was preceded by an intramural esophageal hematoma. Her symptoms persisted after 3 weeks of conservative treatment. Therefore, combined modalities of endoscopic transection and tissue glue application were given, and her symptoms improved gradually.

Development of a novel aortic dissection mouse model and evaluation of drug efficacy using in-vivo assays and database analyses.

Aortic dissection is a life-threatening disease. At present, the only therapeutic strategies available are surgery and antihypertensive drugs. Moreover, the molecular mechanisms underlying the onset of aortic dissection are still unclear. We established a novel aortic dissection model in mice using pharmacologically induced endothelial dysfunction. We then used the Japanese Adverse Drug Event Report database to investigate the role of pitavastatin in preventing the onset of aortic dissection. To induce endothelial dysfunction, Nω-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, was administered to C57BL/6 mice. Three weeks later, angiotensin II (Ang II) and β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, were administered with osmotic mini-pumps. False lumen formation was used as the pathological determinant of aortic dissection. The incidences of aortic dissection and death from aneurysmal rupture were significantly higher in the Nω-nitro-L-arginine methyl ester, Ang II, and BAPN (LAB) group than they were in the Ang II and BAPN (AB) group.Pitavastatin was administered orally to LAB mice. It significantly lowered the incidences of dissection and rupture. It also decreased inflammation and medial degradation, both of which were exacerbated in the LAB group. The Japanese Adverse Drug Event Report database analysis indicated that there were 113 cases of aortic dissection out of 95 090 patients (0.12%) not receiving statins but only six cases out of 16 668 patients receiving statins (0.04%) (odds ratio: 0.30; P = 0.0043). Our results suggest that endothelial dysfunction is associated with the onset of aortic dissection and pitavastatin can help prevent this condition.

Establishment of β-aminopropionitrile-induced aortic dissection model in C57Bl/6J mice

Objective: To establish the mouse aorta dissection (AD) model through drinking water containing β-aminopropionitrile (BAPN). Methods: Forty 3-week-old C57B1/6J male mice were divided into four groups according to randomized block design: control, 0.2, 0.4 and 0.8 g·kg(-1)·d(-1) BAPN groups (dissolving respective dose of BAPN in the drinking water, n=10 each group). Arterial systolic blood pressure and heart rate were measured weekly in conscious, restrained mice using a noninvasive computerized tail-cuff system. Mice those died of rupture of aortic dissecting aneurysm during the study were autopsied and the aorta was examined. After 4 weeks, survived mice were sacrificed by an overdose of sodium pentobarbital and the whole aorta was harvested and analyzed. Results: The incidence of AD and the mortality of ruptured AD was 0 and 0 in control group, 30% (3/10) and 20% (2/10) in 0.2 g·kg(-1)·d(-1) BAPN group, 50% (5/10) and 40% (4/10) in 0.4 g·kg(-1)·d(-1) BAPN group, 90% (9/10) and 70% (7/10) in 0.8 g·kg(-1)·d(-1) BAPN group (both P<0.05 vs. control group). The incidence of AD and the mortality of ruptured AD increased in proportion to BAPN concentration increase. In 0.8 g·kg(-1)·d(-1) BAPN group, 7 mice died of dissecting aneurysm rupture during the experiment, among which 5 dissecting aneurysms were mainly located in the thoracic aorta and 2 dissecting aneurysms in abdominal aorta. The diameters of thoracic aorta and abdominal aorta were (1.38±0.19) and (1.23±0.13) mm in control group, (2.43±1.56) and (1.30±0.26) mm in 0.2 g·kg(-1)·d(-1) BAPN group, (2.45±1.28) and (1.30±0.31) mm in 0.4 g·kg(-1)·d(-1) BAPN group, (2.87±0.57) and (1.95±0.81) mm in 0.8 g·kg(-1)·d(-1) BAPN group (both P<0.05 vs. control group). The diameters of thoracic aorta and abdominal aorta in mice also increased in proportion with BAPN concentration increase. Furthermore, blood-filled false lumen formation and elastic fibers fragmentation were evidenced in hematoxylin-eosin stained and Vitoria blue-Sirius red stained aortic cross-sections of mice in the 0.8 g·kg(-1)·d(-1) BAPN group. Conclusion: BAPN treatment induced aortic dissection model in C57Bl/6J mice can serve as a useful wild-type mouse model for the mechanism and pharmaceutical studies of AD.

Antegrade cystoscopic light source guided laser urethrotomy for the treatment of completely obliterated urethra

ObjectiveA urethral stricture is the narrowing of the urethra caused by scar formation. The etiologies include infection, trauma with total urethral disruption, and iatrogenic procedures. The impact of urethral stricture diseases is very high. Several kinds of endoscopic procedures have become available for managing the disease. Among them, complete obliteration of the urethra during endoscopic procedures remains a challenge for surgeons. We describe a modified procedure in which laser urethrotomy was guided under the light source from an antegrade flexible cystoscope for treating a short completely obliterated urethra. This procedure is indicated if the obliterated segment is less than 10 mm because longer strictures may increase the chance of extra false lumen formation and bleeding. Materials and MethodsForty-three male patients who underwent optical urethrotomy for urethral strictures at Kaohsiung Municipal Ta-Tung Hospital (Kaohsiung, Taiwan) between March 2013 and January 2015 were induced in the study. Five of these patients were diagnosed as having complete urethral obliteration. ResultsIn all five patients with a completely obliterated urethra, retrograde laser incision was performed successfully. Three patients had total bulbar urethral obstruction and two had penile obstruction. All patients experienced improved urination after the procedure. ConclusionOur preliminary data showed that our modified method for treating a completely obliterated urethra yielded satisfactory results. Long-term follow-up and large-scale studies should be conducted to better examine technique efficacy; however, our current results regarding the simple modification of endoscopic urethrotomy seem promising.

Long-term results of probing guided with soft cannula in children with congenital nasolacrimal duct obstruction

To report the results of soft probing in children with congenital nasolacrimal duct obstruction (CNLDO). A prospective, non-randomised interventional study included 158 eyes of 122 children aged 2 months-5 years, with CNLDO. A plastic intravenous catheter sheath supported intraluminally with a guiding metal probe was introduced through the superior canaliculus. During intubation, the plastic cannula was gently introduced through the nasolacrimal system, while the metal probe inside was withdrawn concurrently. After the complete withdrawal of the metal probe, the duct was irrigated with a high pressure saline solution through the plastic cannula. Once the obstruction was totally dissolved and a patent passage was observed, the plastic cannula was withdrawn and the procedure was completed with a nasolacrimal lavage with a gentamycin and dexamethasone combination. Clinically successful results were achieved in 142 eyes (89.8 %). No significant complications occured intraoperatively or postoperatively. In children under age 5, our technique has a high success rate with no significant complications. This method allows probing in a more controlled way. This method may be particularly suitable for surgeons during training, when the most false lumen formation is observed.

Dissection of the Superior Mesenteric Artery which Required Resection of a Large Amount of the Small Intestine and the Colon :

Superior mesenteric artery (SMA) dissection is rare. We herein report about a case of SMA dissection which required resection of a large amount of the small intestine and the colon. A 59-year-old male with vague lower abdominal pain and diarrhea was admitted to our hospital. An erect abdominal X-ray showed niveau. His condition deteriorated and on the fifth day from the onset, an enhanced computed tomography (CT) revealed the SMA was dissected along 3 cm of its length from its origin, and the blood supply to the small intestine was shuttered in association with false lumen formation. Finally, the patient was necessitated an emergency surgery. A grayish ischemic small intestine and ascending colon were seen along with a moderate amount of ascites. The ischemic part of the intestine was resected. Pathological findings revealed coagulation necrosis with inflammatory cell infiltration, blood congestion, and hemorrhage. This coagulation necrosis was compatible with hemorrhagic necrosis due to intestinal ischemia. In conclusion, enhanced CT was available for detecting SMA dissection. If a patient with acute abdomen of unknown origin is encountered, SMA dissection should be ruled out, because ischemic intestine due to SMA occlusion is time-dependent and life-threatening. Furthermore, in the case of extensive bowel resection, the management of short bowel syndrome is thought to be essential.