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Patients with single ventricle heart defects requires a series of staged open-heart procedures, termed Fontan palliation. However, while lifesaving, these operations are associated with significant morbidity and early mortality. The attendant complications are thought to arise in response to the abnormal hemodynamics induced by Fontan palliation, although the pathophysiology underlying these physicochemical changes in cardiovascular and other organs remain unknown. Here, we investigated the microRNA (miRNA) content in serum and serum-derived extracellular vesicles (EVs) by sequencing small RNAs from a physiologically relevant sheep model of the Fontan operation. The differential expression analysis identified the enriched miRNA clusters in (1) serum vs. serum-derived EVs and (2) pre-Fontan EVs vs. post-Fontan EVs. Metascape analysis showed that the overexpressed subset of EV miRNAs by Fontan procedure target liver-specific cells, underscoring a potentially important pathway involved in the liver dysfunction that occurs as a consequence of Fontan palliation. We also found that post-Fontan EV miRNAs were associated with senescence and cell death, whereas pre-Fontan EV miRNAs were associated with stem cell maintenance and epithelial-to-mesenchymal transition. This study shows great potential to identify novel circulating EV biomarkers from Fontan sheep serum that may be used for the diagnosis, prognosis, and therapeutics for patients that have undergone Fontan palliation.

Introduction The efficacy of endovascular treatment for complicated Stanford type B acute aortic dissection is being established. However, aortic events sometimes occur, and some cases require surgical intervention. Report A 52 year old man underwent ascending aorta replacement for Stanford type A acute aortic dissection in August 2016. Post-operative computed tomography (CT) showed residual dissection from the aortic arch to the right common iliac artery and a large re-entry in the right common iliac artery (RCIA). Two months after the operation, CT revealed enlargement of the false lumen of the thoracic aorta and the thoracic aortic diameter. Aiming to reduce the false lumen and remodel the aorta, a three stage operation was performed, as described below. Four months after the dissection, total aortic arch replacement and a frozen elephant trunk insertion were performed as the first stage. Subsequently, as a second stage operation, thoracic endovascular repair (TEVAR) was performed using a Zenith® Dissection Endovascular System (Cook Japan Co., Ltd, Tokyo, Japan), with the aim of expanding the true aortic lumen. The implanted devices were a stent graft for the proximal part and two bare stents for the middle and distal part. As a third stage operation, abdominal aortic endovascular treatment was performed with the purpose of closing the re-entry from the RCIA. However, two years after the three stage operation, CT showed that the thoracic aorta was over 60 mm in diameter. Graft replacement of the thoraco-abdominal aorta was performed. The bare stents were expected to be easily removable from the aorta, but unexpectedly, they were strongly attached to the intima, which made it extremely difficult to perform surgical and aortic operations. Discussion Surgical operations for the aorta can become more difficult after bare stent placement in the aorta., Highlights • Surgical operations on the aorta can be hampered after intra-aortic bare stent placement. • The bare stents and the intima of the true lumen were integrated. • Operability seemed to be relatively smooth when the electric cautery was operated at a high output.

Introduction: Vaccination therapy has long-lasting effects and solves medication non-adherence. However, vaccination therapy on myocardial infarction (MI) has not been developed. Epoxyeicosatrienoic acids (EETs) play an important role in cardio-protective mechanisms through angiogenesis. Here, we developed a soluble epoxide hydrolase (sEH) peptide vaccine to increase the level of EETs and assessed its therapeutic effect for MI-induced heart failure. Hypothesis: We predicted that neovascularization by a sEH vaccine would reduce infract size and prevent post-MI cardiac remodeling. Methods and Results: We made a sEH peptide vaccine based on the amino-acid sequences and administrated the vaccine to rats. ELISA showed that the vaccine induced anti-sEH antibody. Mass spectrometry also confirmed that the vaccine significantly increased blood EETs levels compared to the saline group (P=0.007). We evaluated the effects of the sEH vaccine in the rat model of MI. One week after the left anterior descending artery (LAD) ligation, the vaccinated group significantly suppressed the increase of left ventricular systolic diameter (LVDs) and prevented the decline in left ventricular anterior wall (LVAW), fractional shortening (FS), and ejection function (EF) in echocardiography (P Conclusion: The sEH vaccine therapy for MI induces angiogenesis, which promotes reverse cardiac remodeling. This vaccine is expected to be a treatment option to prevent heart failure after MI.

Myocardial infarction is still a life-threatening disease, even though its prognosis has been improved through the development of percutaneous coronary intervention and pharmacotherapy. In addition, heart failure due to remodeling after myocardial infarction requires lifelong management. The aim of this study was to develop a novel treatment suppressing the myocardial damage done by myocardial infarction. We focused on inhibition of soluble epoxide hydrolase to prolong the activation of epoxyeicosatrienoic acids, which have vasodilatory and anti-inflammatory properties. We successfully made a new vaccine to inactivate soluble epoxide hydrolase, and we have evaluated the effect of the vaccine in a rat myocardial infarction model. In the vaccinated group, the ischemic area was significantly reduced, and cardiac function was significantly preserved. Vaccine treatment clearly increased microvessels in the border area and suppressed fibrosis secondary to myocardial infarction. This soluble epoxide hydrolase vaccine is a novel treatment for improving cardiac function following myocardial infarction.

This is a 3-case report of successful descending thoracic and thoracoabdominal aortic surgery by preserving the spinal perfusion artery (SPA) identified preoperatively. In Case 1, an 85-year-old woman, computed tomography (CT) showed Crawford type Ⅴ thoracoabdominal aortic aneurysm (TAAA:60 mm) and a SPA originated from L2. In Case 2, a 76-year-old man, CT revealed type Ⅳ TAAA( 58 mm) and a SPA originated from Th11. In Case 3, a 74-year-old man, CT detected an infectious pseudoaneurysm(44 mm) in the descending thoracic aorta with 2 SPAs originating from Th10 and L2. The ranges of graft replacement were Th7-Th12, Th12-L4, and Th8-Th10, respectively, while preserving all SPAs. All patients recovered well without postoperative neurological deficits. Although the protective effect of the SPA preservation against the spinal cord ischemia is still controversial, preoperative identification of the SPA was useful for planning a surgical strategy for descending thoracic and thoracoabdominal aortic repair surgery.

Cardiac constructs fabricated using human induced pluripotent stem cells-derived cardiomyocytes (iPSCs-CMs) are useful for evaluating the cardiotoxicity of and cardiac response to new drugs. Previously, we fabricated scaffold-free three-dimensional (3D) tubular cardiac constructs using a bio-3D printer, which can load cardiac spheroids onto a needle array. In this study, we developed a method to measure the contractile force and to evaluate the drug response in cardiac constructs. Specifically, we measured the movement of the needle tip upon contraction of the cardiac constructs on the needle array. The contractile force and beating rate of the cardiac constructs were evaluated by analysing changes in the movement of the needle tip. To evaluate the drug response, contractile properties were measured following treatment with isoproterenol, propranolol, or blebbistatin, in which the movement of the needle tip was increased following isoproterenol treatment, but was decreased following propranolol or blebbistain, treatments. To evaluate cardiotoxicity, contraction and cell viability of the cardiac constructs were measured following doxorubicin treatment. Cell viability was found to decrease with decreasing movement of the needle tip following doxorubicin treatment. Collectively, our results show that this method can aid in evaluating the contractile force of cardiac constructs.

This is a 2-case report of successful aortic repair surgery for the retrosternal giant aortic aneurysm. Our surgical strategy is "deep hypothermia and left ventricular( LV) unloading under cardiopulmonary bypass before approaching to the aortic aneurysm" in case of possible catastrophic bleeding. Case 1, a 64-year-old woman, had a retrosternal pseudoaneurysm (80 mm) at the distal anastomosis of a Dacron graft used to replace the ascending aorta 7 years before. An LV vent tube was cannulated via the right upper pulmonary vein through an inferior T-shaped ministernotomy. Case 2, an 86-year-old woman, had a retrosternal chronic aortic dissecting aneurysm (66 mm). An LV vent cannula was inserted via the LV apex through a left minithoracotomy. Arch replacement and ascending aorta replacement were performed in Case 1 and 2, respectively, without cardiac, neurological, or any other complications. This strategy is safe and useful in a case with complex aortic disease.

This is a 3-case report of mitral valve replacement (MVR) with an On-X mechanical valve followed up to 10 years. Case 1(64-year-old man) and case 2 (66-year-old woman) experienced traffic accident and traumatic event, respectively, in their chronic phase after MVR. Case 1 had multiple bone fractures of the bilateral lower limbs, which was followed by systemic infection and pyogenic spondylitis. He needed long-term antibiotics therapy for more than 4 years. Case 2 fell down at home and severely hit her head, which resulted in a traumatic subarachnoid hemorrhage. She was in a deep coma, and needed discontinuation of anticoagulation therapy for 4 weeks. Case1, 2, and 3(54-year-old man) are doing well in New York Heart Association functional class I without any valve-related thromboembolic or hemorrhagic events at 10, 9 and 8 years after MVR, respectively. On-X valve performance has also been found well maintained in all cases by echocardiography, even after traumatic accident or discontinuation of anticoagulation in Case 1 and 2. In this report, the On-X mechanical valve demonstrated good midterm result of its valve performance in the mitral position and its potential advantages in antithrombogenicity.

An 80-year-old man had undergone Y-graft replacement for ruptured abdominal aortic aneurysm followed by bioprosthetic aortic valve replacement. Follow-up computed tomography revealed a 65-mm aneurysm at the distal aortic arch. We selected endovascular surgery because of the patient's high-risk condition, and the extreme curvature of the 8-mm artificial blood vessels led us to adopt a transapical approach. No signs of deterioration of the bioprosthesis were noted, and the patient's hemodynamic condition remained stable during surgery. Transapical thoracic endovascular aortic repair through a pre-existent aortic bioprosthesis is an efficient alternative approach for treating aortic aneurysm, even after bioprosthetic aortic valve replacement. Keywords: Transapical, TEVAR, Endovascular aortic repair

The safety and therapeutic efficacy of new drugs are evaluated using animal testing. However, besides the relatively time-consuming and costly process, the differences in drug response between humans and animals and potential adverse effects on the heart lead to the discontinuation of new drug development. Thus, alternative approaches to animal testing are highly desired. The drug response and cardiotoxicity of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are conventionally evaluated using cell seeding and culture method (two-dimensional (2D) culture method). This method allows the measurement of the field potential duration and action potential of each cardiomyocyte by using multi-electrode arrays. However, compared to cardiomyocytes in vivo, 2D cultured hiPSC-CMs have low cell density and interaction between cells and with the ECM, and thus have a different contractile behavior. This issue has been addressed by using tissue engineering to fabricate three-dimensional (3D) cardiac constructs from in vitro cultured hiPSC-CMs. Tissue engineering can be categorized into two groups: scaffold-based and scaffold-free. In scaffold-based tissue engineering, scaffolds such as collagen and fibrin gel are used as a 3D culture environment for cells. The cells seeded in the scaffold show cardiac-specific function and drug response. In contrast, in scaffold-free tissue engineering, 3D cardiac constructs are fabricated without a scaffold. These cardiac constructs have high cell density and show cell-to-cell interaction. In this review, we summarize the characteristics of scaffold-based and scaffold-free cardiac tissue engineering and discuss the applications of fabricated cardiac constructs for drug evaluation.

Before they are used in the clinical setting, the effectiveness of artificially produced human-derived tissue-engineered medical products should be verified in an immunodeficient animal model, such as severe combined immunodeficient mice. However, small animal models are not sufficient to evaluate large-sized products for human use. Thus, an immunodeficient large animal model is necessary in order to properly evaluate the clinical efficacy of human-derived tissue-engineered products, such as artificial grafts. Here we report the development of an immunodeficient pig model, the operational immunodeficient pig (OIDP), by surgically removing the thymus and spleen, and creating a controlled immunosuppressive protocol using a combination of drugs commonly used in the clinical setting. We find that this model allows the long-term accommodation of artificial human vascular grafts. The development of the OIDP is an essential step towards a comprehensive and clinically relevant evaluation of human cell regeneration strategies at the preclinical stage., The development of tissue-engineered vascular grafts heavily relies on the availability of large animal models that allow long-term assessment of graft patency. Here Itoh et al. propose a novel model of immunodeficient pigs that allows long-term accommodation of human cell-derived three-dimensional bioprinted vascular tubes.

A 78-year-old man underwent endovascular abdominal aortic aneurysm repair (EVAR) for a true aortic aneurysm. He developed sudden abdominal pain 4 hr after EVAR. Angiography revealed a dissected aneurysm of the middle colic artery (MCA). Despite conservative treatment, follow-up computed tomography revealed an expanded aneurysm of the MCA. We therefore performed coil embolization of the dissected MCA to prevent a rupture of the aneurysm. There has never been a reported case of acute dissection of the MCA immediately after EVAR that was not caused by catheters. In this report, we discuss the possible underlying mechanisms and the optimal therapeutic strategy for this rare complication.

Before they are used in the clinical setting, the effectiveness of artificially produced human-derived tissue-engineered medical products should be verified in an immunodeficient animal model, such as severe combined immunodeficient mice. However, small animal models are not sufficient to evaluate large-sized products for human use. Thus, an immunodeficient large animal model is necessary in order to properly evaluate the clinical efficacy of human-derived tissue-engineered products, such as artificial grafts. Here we report the development of an immunodeficient pig model, the operational immunodeficient pig (OIDP), by surgically removing the thymus and spleen, and creating a controlled immunosuppressive protocol using a combination of drugs commonly used in the clinical setting. We find that this model allows the long-term accommodation of artificial human vascular grafts. The development of the OIDP is an essential step towards a comprehensive and clinically relevant evaluation of human cell regeneration strategies at the preclinical stage.

Four pairs of raw and acid-washed brown coals were subjected to pyrolysis and in-situ steam gasification at 900 °C in fixed-bed reactors with or without forced gas flow through the bed of char particles. The chars from the acid-washed coals were gasified obeying a first-order kinetics with respect to the fraction of unconverted char regardless of the presence/absence of forced gas flow. Its presence/absence considerably influenced the gasification kinetics of the chars from the raw coals, even altering the manner of change in the rate of gasification with time and the char conversion, such as the apparent order of reaction. It was found that alkali and alkaline earth metallic (AAEM) species were allowed to stay in/on the char in the absence of the forced gas flow but volatilized extensively in its presence. Thus, the catalysis of AAEM species diminished in the presence of forced gas flow much quicker than in its absence, in which the catalysis was lost exclusively by intraparticle deactivation of AAEM spe...