A case of Marfan syndrome with massive haemoptysis from collaterals of the lateral thoracic artery.

BACKGROUND: Marfan Syndrome (MFS) is a heritable connective tissue disorder with a high degree of clinical variability including respiratory diseases; a rare case of MFS with massive intrathoracic bleeding has been reported recently. CASE PRESENTATION: A 32-year-old man who had been diagnosed with MFS underwent a Bentall operation with artificial valve replacement for aortic dissection and regurgitation of an aortic valve in 2012. Warfarin was started postoperatively, and the dosage was gradually increased until 2017, when the patient was transported to our hospital due to sudden massive haemoptysis. Computed tomography (CT) with a maximum intensity projection (MIP) revealed several giant pulmonary cysts with fluid levels in the apex of the right lung with an abnormal vessel from the right subclavian artery. Transcatheter arterial embolization was performed with angiography and haemostasis was achieved, which suggested that the bleeding vessel was the lateral thoracic artery (LTA) branch. CT taken before the incident indicated thickening of the cystic wall adjacent to the thorax; therefore, it was postulated that the bleeding originated from fragile anastomoses between the LTA and pulmonary or bronchial arteries. It appears that the vessels exhibited inflammation that began postoperatively, which extended to the cysts. CONCLUSION: We experienced a case of MFS with massive haemoptysis from the right LTA. We have to be aware of the possibility that massive haemoptysis could be induced in MFS with inflamed pulmonary cysts.

Traditional Chinese patent medicine Zhixiong Capsule (ZXC) alleviated formed atherosclerotic plaque in rat thoracic artery and the mechanism investigation including blood-dissolved-component-based network pharmacology analysis and biochemical validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese patent medicine Zhixiong Capsule (ZXC) is the equal mixture of the extract of leech, Ligusticum chuanxiong Hort., Salvia miltiorrhiza Bunge, Leonurus japonicus Houtt., and Pueraria lobate (Willd.) Ohwi, which have been long used against inflammation, hyperlipidemia or blood stasis. In our previous study, ZXC showed good efficacy in preventing atherosclerosis (AS) plaque formation in rabbits. AIM OF THE STUDY: In actual clinic practice, patients are more likely to receive treatments after AS plaque formation. Therefore, the efficacy of ZXC on formed AS plaques and the underlying mechanisms were further investigated in this study. MATERIALS AND METHODS: Simvastatin (positive control) and ZXC (420 mg/kg and 840 mg/kg) were administrated to rats which first received long-term high fat diet administration (12 weeks). The blood lipid profiles of rats were monitored during the whole experiment, and the thoracic arteries were collected at the end of experiment for AS assessment (18th week). The blood-dissolved ZXC components were determined using an UPLC-QTOF-MS method, and the attained components were then used for network pharmacology analysis to predict the key ZXC components and targets. At last, the predicted targets were validated by ELISA and western blot methods. RESULTS: ZXC administration showed good blood lipid-lowering effect by significantly reduced LDL-C and TC levels in rats while significantly increased HDL-C level. Compared with model group, simvastatin, low- and high-dose of ZXC administration decreased the ratio of intimal area and medial area by 81.1%, 71.1% and 71.4%, respectively (p < 0.01), and significantly alleviated collagen deposition and mineralization in rat arteries. It was found by network pharmacology analysis that leech and four components (namely daidzein, 4-methylenemiltirone, isorhamnetin and 2-isopropyl-8-methylphenanthrene-3,4-dione) are vital components for the anti-AS efficacy of ZXC. Combing the results from biochemical validation, IL-4, IL-13, MAPK1, MAPK14, JUN and P53 were confirmed as key targets of ZXC. CONCLUSION: It could be concluded that ZXC has value as an anti-AS agent in clinical treatment against formed AS plaque at the current application dosage.

Multifunctional cationic nanosystems for nucleic acid therapy of thoracic aortic dissection.

Thoracic aortic dissection (TAD) is an aggressive vascular disease that requires early diagnosis and effective treatment. However, due to the particular vascular structure and narrowness of lesion location, there are no effective drug delivery systems for the therapy of TAD. Here, we report a multifunctional delivery nanosystem (TP-Gd/miRNA-ColIV) composed of gadolinium-chelated tannic acid (TA), low-toxic cationic PGEA (ethanolamine-aminated poly(glycidyl methacrylate)) and type IV collagen targeted peptide (ColIV) for targeted nucleic acid therapy, early diagnosis and noninvasive monitoring of TAD. Such targeted therapy with miR-145 exhibits impressive performances in stabilizing the vascular structures and preventing the deterioration of TAD. After the treatment with TP-Gd/miR-145-ColIV, nearly no dissection occurs in the thoracic aortic arches of the mice with TAD model. Moreover, TP-Gd/miRNA-ColIV also demonstrates good magnetic resonance imaging (MRI) ability and can be used to noninvasively monitor the development conditions of TAD.

Histomorphometric analysis of the human internal thoracic artery and relationship with cardiovascular risk factors.

In this study, we aimed at performing a histomorphometric analysis of human left internal thoracic artery (ITA) samples as well as at correlating the histomorphometric findings with the clinical profile, including risk factors and medication. Distal segments of ITA were obtained from 54 patients undergoing coronary artery bypass grafting. Histological observation was performed in paraffin-embedded transverse sections of ITA through four staining protocols: hematoxylin-eosin, van Gieson, Masson's trichrome and von Kossa. Morphometric analysis included the intimal width (IW), medial width (MW) and intima/media ratio (IMR). No overt atherosclerotic lesions were observed. Mild calcifications were observed across the vascular wall layers in almost all samples. Multivariable linear regression analysis showed associations between IW and IMR and the following clinical variables: age, gender, kidney function expressed as eGFR and myocardial infarction history. Age (odds ratio = 1.16, P = 0.004), female gender (odds ratio = 11.34, P = 0.011), eGFR (odds ratio = 1.03, P = 0.059) and myocardial infarction history (odds ratio = 4.81, P = 0.040) were identified as the main clinical predictors for intimal hyperplasia. Preatherosclerotic lesions in ITA samples from patients undergoing coronary revascularization were associated not only with classical cardiovascular risk factors such as age and gender, but also with other clinical variables, namely kidney function and myocardial infarction history.

Coverage of visible intercostal and lumbar segmental arteries can predict the volume of cerebrospinal fluid drainage in elective endovascular repair of descending thoracic and thoracoabdominal aortic disease: a pilot study.

OBJECTIVES: Our goal was to identify anatomical and physiological factors that could predict the amount of cerebrospinal fluid (CSF) drainage in patients undergoing elective endovascular repair of descending thoracic and thoracoabdominal aortic disease. METHODS: All consecutive elective endovascular procedures performed for descending thoracic or thoracoabdominal aortic disease between January 2015 and December 2017 were included in the study. Routine use of CSF drainage was established in all patients. The goal of drainage was to reach a spinal fluid pressure of 10-12 mmHg by draining in 5-15-ml aliquots. The number of visible intercostal and lumbar segmental arteries (SAs) was evaluated before and after endovascular repair. The covering ratio of SAs was calculated as covered preoperative SAs/total preoperative SAs. RESULTS: Twenty-four consecutive patients were included in the final analysis. The indication for the intervention was a descending thoracic aneurysm in 13 cases, a thoracoabdominal aneurysm in 4 cases and a chronic type B dissection in 7 cases. The procedure performed was thoracic endovascular aortic repair in 20 cases and fenestrated endovascular aneurysm repair in 4 cases. None of the patients developed spinal cord ischaemia. The mean volume of CSF drained was 46 ml. The mean length of aortic coverage was 231 mm. The mean number of total preoperative SAs and of covered preoperative SAs was, respectively, 22 and 9. The volume of CSF drained was significantly correlated with all these variables (length of aortic coverage, total visible SAs and covered SAs), but the most powerful correlation was individuated with the covering ratio of SAs. CONCLUSIONS: Our findings suggest that the percentage of intercostal and lumbar SAs covered by placement of a stent graft can predict the volume of CSF drained in patients undergoing elective endovascular repair of descending thoracic and thoracoabdominal aortic disease.

The toxic effects of monosodium glutamate (MSG) - The involvement of nitric oxide, prostanoids and potassium channels in the reactivity of thoracic arteries in MSG-obese rats.

We investigated the potential effects of monosodium glutamate (MSG)-induced obesity with regards to nitric oxide and prostanoid production, as well as potassium channel function, in rat thoracic arteries. Newborn male Wistar rats were injected intraperitoneally with typically reported MSG (4.0 mg/g) once daily for 4 consecutive days. At 90 days postnatal, the rats were sacrificed and the thoracic aortas were evaluated for vascular responses and for prostanoid production. Nitric oxide was studied with calcium ionophore (A23187), acetylcholine (ACh) and sodium nitroprusside (SNP). The release of prostanoids was measured under basal and ACh-stimulated conditions, and the vasomotor effect of exogenous thromboxane A2 mimetic, U46619 was assessed. Potassium channel activities were analyzed using an NS1619 opener for BKCa channels and pinacidil for KATP channels. Arteries from MSG-obese rats exhibited a reduced maximal contraction to potassium chloride and hyper-responsiveness to U46619, suggesting that MSG also alters the responsiveness of vascular smooth muscles. The endothelium-dependent relaxation to ACh and A23817 was attenuated, suggesting low nitric oxide bioavailability. The hypersensitivity of arteries to an exogenous nitric oxide donor, SNP, occurred. The secondary contraction to A23817 was augmented, suggesting increased activation of the prostanoid receptor. The prostanoid release was increased in both basal- and acetylcholine-stimulated rings. In addition, down-regulation of KATP and BKCa channels influenced hyperpolarizing mechanisms. Our findings suggest that increased prostanoid production and hypersensitivity to thromboxane A2 together with down-regulation of potassium channels and low nitric oxide bioavailability may contribute to the increase in blood pressure found in adult MSG-obese male rats.

Ochronosis of Mitral Valve and Coronary Arteries.

Cardiac ochronosis is a rare complication of alkaptonuria, a disorder of tyrosine metabolism characterized by a triad of dark urine, pigmentation of tissues, and ochronotic arthropathies. When present, cardiac ochronosis generally affects the aortic valve, resulting in aortic stenosis. More rarely, it may affect the mitral valve and the coronary arteries. This report describes the case of a 67-year-old woman with a history of alkaptonuria with severe ochronosis of the coronary arteries and mitral valve who required coronary artery bypass and mitral valve replacement.

Differentially expressed genes and canonical pathway expression in human atherosclerotic plaques - Tampere Vascular Study.

Cardiovascular diseases due to atherosclerosis are the leading cause of death globally. We aimed to investigate the potentially altered gene and pathway expression in advanced peripheral atherosclerotic plaques in comparison to healthy control arteries. Gene expression analysis was performed (Illumina HumanHT-12 version 3 Expression BeadChip) for 68 advanced atherosclerotic plaques (15 aortic, 29 carotid and 24 femoral plaques) and 28 controls (left internal thoracic artery (LITA)) from Tampere Vascular Study. Dysregulation of individual genes was compared to healthy controls and between plaques from different arterial beds and Ingenuity pathway analysis was conducted on genes with a fold change (FC) > ±1.5 and false discovery rate (FDR) < 0.05. 787 genes were significantly differentially expressed in atherosclerotic plaques. The most up-regulated genes were osteopontin and multiple MMPs, and the most down-regulated were cell death-inducing DFFA-like effector C and A (CIDEC, CIDEA) and apolipoprotein D (FC > 20). 156 pathways were differentially expressed in atherosclerotic plaques, mostly inflammation-related, especially related with leukocyte trafficking and signaling. In artery specific plaque analysis 50.4% of canonical pathways and 41.2% GO terms differentially expressed were in common for all three arterial beds. Our results confirm the inflammatory nature of advanced atherosclerosis and show novel pathway differences between different arterial beds.

Variants of genes encoding collagens and matrix metalloproteinase system increased the risk of aortic dissection.

Aortic dissection (AD) is a devastating, heterogeneous condition of aorta. The homeostasis between collagens and matrix metalloproteases (MMPs)/tissue inhibitors of MMPs (TIMPs) system in the extracellular matrix plays an important role for structure and functions of aorta. However, our knowledge on association between variants of genes in this system and pathogenesis of AD is very limited. We analyzed all yet known coding human genes of collagens (45 genes), MMPs/TIMPs (27 genes) in 702 sporadic AD patients and in 163 matched healthy controls, by using massively targeted next-generation and Sanger sequencing. To define the pathogenesis of potential disease-causing candidate genes, we performed transcriptome sequencing and pedigree co-segregation analysis in some genes and generated Col5a2 knockout rats. We identified 257 pathogenic or likely pathogenic variants which involved 88.89% (64/72) genes in collagens-MMPs/TIMPs system and accounted for 31.05% (218/702) sporadic AD patients. In them, 84.86% patients (185/218) carried one variant, 12.84% two variants and 2.30% more than two variants. Importantly, we identified 52 novel probably pathogenic loss-of-function (LOF) variants (20 nonsense, 16 frameshift, 14 splice sites, one stop-loss, one initiation codon) in 11.06% (50/452) AD patients, which were absent in 163 controls (P=2.5×10-5). Transcriptome sequencing revealed that identified variants induced dyshomeostasis in expression of collagens-TIMPs/MMPs systems. The Col5a2 -/- rats manifested growth retardation and aortic dysplasia. Our study provides a first comprehensive map of genetic alterations in collagens-MMPs/TIMPs system in sporadic AD patients and suggests that variants of these genes contribute largely to AD pathogenesis.

Advanced glycation end products impair the functions of saphenous vein but not thoracic artery smooth muscle cells through RAGE/MAPK signalling pathway in diabetes.

Saphenous vein (SV) and internal thoracic artery (ITA) are commonly used bypass conduits. However, graft failure occurs in SV rather than in ITA, especially in diabetes (DM). The mechanism for this difference has not been fully understood. Accumulation of advanced glycation end products (AGEs) and activation of AGEs receptor (RAGE) could accelerate smooth muscle cells (SMC) proliferation in DM, we thus asked whether AGEs-RAGE could mediate the differences between SMC from SV (SMCV ) and from ITA (SMCA ). Twenty-five patients with DM and other 25 patients without DM were enclosed in DM and control group, respectively. AGEs (100 µg/ml) were added to cultured SMCA and SMCV obtained at coronary artery bypass graft (CABG) and proliferative rates were determined. Transcript expression, phosphorylation or protein expression levels of MAP kinase family (ERK, p38 and JNK), matrix metalloproteinases (MMP)-2 and MMP-9 were analysed by real-time PCR, Western-blot or immunofluorescence staining, respectively. Compared with paired SMCA , SMCV showed significantly increased proliferation rate, MAP kinase family phosphorylation, and MMP-2/9 expression in both groups, especially in DM group. The responses of SMCV induced by AGEs were significantly larger in DM than in control group, which could be suppressed by inhibition of RAGE and ERK. However, all the cellular events of SMCV were not found in paired SMCA . This study suggests that AGEs-RAGE could induce the proliferation of SMCV but not SMCA via MAP kinase pathway in DM. It is the intrinsic 'inactive' tendency of SMCA that contributes to the different rates of graft disease between SV and ITA after CABG.

Hypertrophic aortic branches can potentially cause critical problems during minimally invasive cardiac surgery.

Here we present two cases in which hypertrophic aortic branches caused trouble during minimally invasive cardiac surgery. We performed mitral valvuloplasty with the Maze procedure in Case 1 and mitral valvuloplasty with aortic valve replacement in Case 2 via mini-thoracotomy. In preoperative computed tomography scan, we did not note a hypertrophic bronchial artery in Case 1 or a dilated intercostal artery in Case 2. The right atrium was distended after aortic cross-clamping and perioperative myocardial infarction occurred in Case 1. Whereas, we could effectively deal with this situation in Case 2. The increased pulmonary blood flow can potentially cause critical problems during minimally invasive surgery. Sufficient venting of the right ventricle and secure myocardial protection is the key to perform safe surgery in the presence of dilated aortic branches. However, surgeons should not hesitate to convert to sternotomy under poor surgical exposure despite sufficient venting.

Ruptured intercostal artery pseudoaneurysm: a rare cause of acute back pain.

A 63-year-old man with no relevant medical history presented with acute non-traumatic back pain and was found to have a T8 intercostal artery pseudoaneurysm associated with haemomediastinum on CT of the chest. He was taken to angiography with interventional radiology and the aneurysm was coiled without complication.

Six-month healing of the nonocclusive coronary anastomotic connector in an off-pump porcine bypass model.

OBJECTIVE: This pilot study evaluates the anastomotic healing of the Excimer Laser Assisted Nonocclusive Anastomosis coronary connector at 6 months in a porcine off-pump coronary artery bypass (OPCAB) model. METHODS: Left internal thoracic artery to left anterior descending coronary artery bypass in two animals and left internal thoracic artery to left anterior descending coronary artery and right internal thoracic artery to right coronary artery bypasses in one animal were evaluated intraoperatively and at 6 months. The anastomoses (n = 4) were examined by angiography, intravascular ultrasound, optical coherence tomography, scanning electron microscopy, and histology. RESULTS: At follow-up, all anastomoses (n = 4) were fully patent (FitzGibbon grade A). Scanning electron microscopy demonstrated complete endothelial coverage of the anastomotic surface, and histology showed minimal streamlining intimal hyperplasia. The in vivo intravascular ultrasound and optical coherence tomography acquisitions confirmed histologic findings. Optical coherence tomography demonstrated 0.06-mm intimal coverage of the intraluminal part of the connector along the full circumference of the anastomosis. CONCLUSIONS: In this pilot study, the Excimer Laser Assisted Nonocclusive Anastomosis coronary connector showed an excellent healing response on the long-term in the porcine OPCAB model. Hence, this new concept might be a potential alternative to hand-sutured anastomosis in (minimally invasive) OPCAB surgery.

Multiple aneurysms of thoracic spinal cord arteries presenting with spinal infarction and subarachnoid hemorrhage: case report and literature review.

BACKGROUND AND IMPORTANCE: Arterial aneurysms of the spinal cord are rare. Their pathogenesis is variable, and the therapeutic strategies remain controversial, because their natural history is unclear. We report a case of multiple dissecting aneurysms of radiculomedullary and radiculopial arteries presenting with spinal infarction and subarachnoid hemorrhage, which spontaneously resolved. CLINICAL PRESENTATION: A 67-year-old woman was hospitalized owing to sudden onset of severe back pain with discomfort in the lower extremities. Two days later, she again experienced sudden back pain accompanied by paraparesis and sphincter disturbance. Magnetic resonance imaging of the thoracic spinal cord showed 2 intradural masses of heterogeneous intensity at the levels of T-8 and T-10, spinal infarction, and subarachnoid hemorrhage. Spinal angiography revealed a "pearls and strings" aspect of a radiculomedullary artery arising from the left T-11 and a fusiform aneurysm of a radiculopial artery arising from the left T-8. Infectious and immunological evaluations failed to show any anomaly. Spontaneous dissections were suspected. Conservative treatment was proposed, and the patient's clinical course remained uneventful. Follow-up magnetic resonance imaging and spinal angiography performed 2 months after onset showed disappearance of both arterial lesions. CONCLUSION: Arterial dissections of spinal radicular arteries can resolve spontaneously and be managed conservatively. We propose a classification of the pathogenesis of spinal arterial aneurysm to clarify appropriate treatment strategies by a literature review.

Descending thoracic aortic surgery: update on mortality, morbidity, risk assessment and management.

PURPOSE OF REVIEW: The purpose of this review is to summarize the literature on thoracic aortic surgery, as well as key management guidelines in the perioperative period. This is particularly timely, as endovascular techniques continue to evolve and become more available. RECENT FINDINGS: Endovascular treatment of thoracic aortic disease is expanding in applications and case complexity. SUMMARY: With the expanded use of endovascular techniques to treat aortic disease, midterm and long-term outcome studies and comparisons to open surgical approach are now being published with increasing frequency. This review analyzes the available literature on preventing adverse outcomes after descending thoracic aortic surgery, with specific attention to mortality, morbidity, risk assessment and management in the perioperative setting.

Loss of compliance in small arteries, but not in conduit arteries, after 6 weeks exposure to high fat diet.

Arterial stiffness is a key marker in metabolic diseases and can be evaluated by arterial compliance. Most compliance measurements are performed in large conduit arteries in advanced stage of metabolic diseases, which may not provide information on mechanisms associated with the initiation of the pathology. For this reason, we compared arterial compliance of two different size arteries: carotid and a smaller artery (thoracodorsal artery, TDA). The arterial compliance was compared between control and high fat-fed mice for 6 weeks. We show that the compliance of the TDAs was dramatically reduced in high fat-fed mice whereas the compliance of the carotids remained unchanged. An abundance of collagen deposition in the media/adventitia of the carotids and TDAs was observed in high fat-fed mice. These results demonstrate that the structural and mechanical properties of small arteries are rapidly altered even after only 6 weeks of high fat feeding.

Left pleural effusion and fever of unknown origin--a clue to thoracic arterial pathology.

The subset of patients who have both fever of unknown origin (FUO) and a nondiagnostic pleural effusion on presentation has not been previously investigated. A retrospective search of all patients classified as 'classic' FUO one week after admission to a department of general internal medicine identified 71 patients over 15 years. Seven were found to have associated pleural effusion(s) on admission (9.8%). In three patients thoracic large vessel pathology was diagnosed (chronic aortic dissection, giant cell arteritis and Takayasu arteritis). In these patients, the pleural effusion was predominantly left-sided, small to moderate in amount and nondiagnostic on thoracentesis. The effusions resolved spontaneously or with appropriate treatment. Thus, in patients with prolonged fever and systemic symptoms, a 'bland' left-sided pleural effusion may be a diagnostic clue to underlying inflammation of large thoracic arteries. Pleural irritation due to its anatomical proximity to the large arteries on the left side of the thorax may underlie the pathogenesis. Recognition of this sign may lead to a more timely diagnosis of occult thoracic large vessel pathology.

A spontaneous intercostal artery hemorrhage in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that can lead to damage to several vital organs. Antiphospholipid syndrome (APS), manifesting as vascular thromboembolic events and morbidities of pregnancy in the presence of antiphospholipid antibodies (aPL), has been described in patients with SLE. Catastrophic antiphospholipid syndrome (CAPS), in contradistinction to APS, is defined as three or more organs affected by thrombotic microangiopathy in patients demonstrating aPL and can result in mortality up to 50%. We describe a unique SLE patient who was diagnosed with recurrent APS presented with axillary venous thrombosis and subsequent superficial edema and compartment syndrome. The CAPS followed and revealed thromboses over liver, spleen, and acute pancreatitis. The spontaneous hemorrhage of left fourth intercostal artery (ICA) and left axillary artery occured at the same time without vasculitis or severe trauma. Though emergency transcatheter arterial embolization (TAE) of the left fourth ICA was successfully accomplished by the radiologist. The repeated computed tomography angiogram of chest demonstrated remission of ruptured ICA. Nevertheless, the patient died of diffuse alveolar hemorrhage and respiratory failure and shock. Both disseminated intravascular coagulation (DIC) and CAPS share similar characteristics encompassing thrombotic microangiopathy, bleeding, thromboembolism, and multiple organ dysfunction. It is difficult to distinguish between them, especially in cases such as our uremic SLE patient with a calamitous disease progression. The emphasis of treatment for DIC is on platelet and fresh plasma transfusion, in contrast with anti-coagulant for CAPS. To the best of our knowledge, this is the first report describing ICA hemorrhage in an SLE patient without vasculitis or aneurysm. The lupus flare initiated a pathological immunological cascade and resulted in the CAPS and the vascular damage.