Low-flow perfusion technique for shaggy aortic arch.

BACKGROUND: The most common complication of thoracic aortic disease with shaggy aorta is cerebral infarction. We have performed "low-flow perfusion" as a method of extracorporeal circulation to prevent cerebral embolism in patients with strong atherosclerotic lesions in the aortic arch. METHODS: "Low-flow perfusion" is a method in which cardiopulmonary bypass is started by partial blood removal, approaching deep hypothermia while maintaining self-cardiac output. We compared the outcomes of 12 patients who underwent the "low-flow perfusion" method (Group L) with those of 12 who underwent normal extracorporeal circulation (Group N) during aortic arch surgery since 2019. RESULTS: Group L consisted of 8 males with an average age of 73 years old, and Group N consisted of 6 males with an average age of 73 years old. The average time from the start of cooling to ventricular fibrillation was 9.5 min in Group L and 3.6 min in Group N (p < 0.01). The eardrum temperature when ventricular fibrillation was reached was 28.2 °C in Group L and 32.5 °C in Group N (p = 0.01). A blood flow analysis also revealed low wall shear stress on the lesser curvature of the aortic arch. CONCLUSION: With this method, the intracranial temperature was sufficiently low at the time of ventricular fibrillation, and there was no need to increase the total pump flow. The low-flow perfusion method can prevent cerebral embolism by preventing atheroma destruction by the blood flow jet while maintaining the self-cardiac output during the cooling process.

Empagliflozin Suppresses the Differentiation/Maturation of Human Epicardial Preadipocytes and Improves Paracrine Secretome Profile.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce epicardial adipose tissue (EAT) in humans, enhancing cardioprotective effects on heart failure and atrial fibrillation. We investigated the direct effect of the SGLT2 inhibitor empagliflozin on human primary epicardial adipocytes and preadipocytes. SGLT2 is primarily expressed in human preadipocytes in the EAT. The expression levels of SGLT2 significantly diminished when the preadipocytes were terminally differentiated. Adipogenesis of preadipocytes was attenuated by empagliflozin treatment without affecting cell proliferation. The messenger RNA levels and secreted protein levels of interleukin 6 and monocyte chemoattractant protein 1 were significantly decreased in empagliflozin-treated adipocytes. Coculture of human induced pluripotent stem cell-derived atrial cardiomyocytes and adipocytes pretreated with or without empagliflozin revealed that empagliflozin significantly suppressed reactive oxygen species. IL6 messenger RNA expression in human EAT showed significant clinically relevant associations. Empagliflozin suppresses human epicardial preadipocyte differentiation/maturation, likely inhibiting epicardial adipogenesis and improving the paracrine secretome profile of EAT, particularly by regulating IL6 expression.

Mechanism of action of non-camptothecin inhibitor Genz-644282 in topoisomerase I inhibition.

Topoisomerase I (TOP1) controls the topological state of DNA during DNA replication, and its dysfunction due to treatment with an inhibitor, such as camptothecin (CPT), causes replication arrest and cell death. Although CPT has excellent cytotoxicity, it has the disadvantage of instability under physiological conditions. Therefore, new types of TOP1 inhibitor have attracted particular attention. Here, we characterised the effect of a non-camptothecin inhibitor, Genz-644282 (Genz). First, we found that treatment with Genz showed cytotoxicity by introducing double-strand breaks (DSBs), which was suppressed by co-treatment with aphidicolin. Genz-induced DSB formation required the functions of TOP1. Next, we explored the advantages of Genz over CPT and found it was effective against CPT-resistant TOP1 carrying either N722S or N722A mutation. The effect of Genz was also confirmed at the cellular level using a CPT-resistant cell line carrying N722S mutation in the TOP1 gene. Moreover, we found arginine residue 364 plays a crucial role for the binding of Genz. Because tyrosine residue 723 is the active centre for DNA cleavage and re-ligation by TOP1, asparagine residue 722 plays crucial roles in the accessibility of the drug. Here, we discuss the mechanism of action of Genz on TOP1 inhibition.

Three-month outcomes of aortic valve reconstruction using collagenous membranes (biosheets) produced by in-body tissue architecture in a goat model: a preliminary study.

BACKGROUND: Autologous pericardium is widely used as a plastic material in intracardiac structures, in the pulmonary artery, and in aortic valve leaflets. For aortic valve reconstruction (AVRec) using the Ozaki procedure, it has produced excellent clinical results over a 10-year period. In-body tissue architecture (iBTA), which is based on the phenomenon of tissue encapsulation of foreign materials, can be used to prepare autologous prosthetic tissues. In this preliminary study, we examined whether biosheets can be used as valve leaflet material for glutaraldehyde-free AVRec by subchronic implantation experiments in goats and evaluated its performance compared with glutaraldehyde-treated autologous pericardium for AVRec. METHODS: Biosheets were prepared by embedding molds for two months into the dorsal subcutaneous spaces of goats. Autogenic biosheets (n = 4) cut into the shape of the valve were then implanted to the aortic valve annulus of four goats for three months without glutaraldehyde treatment. Autologous pericardium (n = 4) was used in four goats as a control. Valve function was observed using echocardiography. RESULTS: All goats survived the three-month study period. With biosheets, the leaflet surfaces were very smooth and, on histology, partially covered with a thin neointima (including endothelial cells). Biosheets were more thoroughly assimilated into the aortic root compared with autologous pericardium. CONCLUSIONS: For the first time, biosheets were used for large animal AVRec. Biosheets could function as leaflets in the aortic position and may have the ability to assimilate into native valves.

Aortic valve neocuspidization with in-body tissue-engineered autologous membranes: preliminary results in a long-term goat model.

OBJECTIVES: Aortic valve neocuspidization has shown satisfactory clinical outcomes; however, autologous pericardium durability is a concern for young patients. This study applied an autologous collagenous membrane (Biosheet®), produced by in-body tissue architecture, to aortic valve neocuspidization and investigated its long-term outcome in a goat model. METHODS: Moulds were embedded subcutaneously in 6 goats. After 2 months, Biosheets formed in the moulds. We performed aortic valve neocuspidization using a portion of the sheets with a thickness of 0.20-0.35 mm, measured by optical coherence tomography. Animals were subjected to echocardiography and histological evaluation at 6 months (n = 3) and 12 months (n = 3). As a control, the glutaraldehyde-treated autologous pericardium was used in 4 goats that were similarly evaluated at 12 months. RESULTS: All animals survived the scheduled period. At 6 months, Biosheets maintained valve function and showed a regeneration response: fusion to the annulus, cell infiltration to the leaflets and appearance of elastic fibres at the ventricular side. After 12 months, the regenerative structure had changed little without regression, and there was negligible calcification in the 1/9 leaflets. However, all cases had one leaflet tear, resulting in moderate-to-severe aortic regurgitation. In the pericardium group, three-fourths of the animals experienced moderate-to-severe aortic regurgitation with a high rate of calcification (9/12 leaflets). CONCLUSIONS: Biosheets may have regeneration potential and anti-calcification properties in contrast to autologous pericardium. However, in order to obtain reliable outcome, further improvements are required to strictly control and optimize its thickness, density and homogeneity.

True Aneurysm of the Left Main Trunk in a Marfan Syndrome Patient at Remote Period after Bentall Operation and Total Arch Replacement: A Case Report.

In 2002, a 37-year-old male with Marfan syndrome underwent the Bentall operation, total arch replacement, and aortobifemoral bypass for DeBakey type IIIb chronic aortic dissection, annuloaortic ectasia, and aortic regurgitation. In 2007, mild mitral regurgitation (MR) caused by mitral valve prolapse was identified. In April 2017, echocardiography revealed the worsening of MR and moderate tricuspid regurgitation (TR). Moreover, coronary angiography (CAG) revealed a coronary artery aneurysm in the left main trunk (LMT). In August 2017, the patient underwent mitral valve replacement (MVR), tricuspid annuloplasty (TAP), and coronary artery reconstruction. We reconstructed the LMT aneurysm using an artificial graft. True aneurysm of the coronary artery complicated with Marfan syndrome is a rare complication that has seldom been reported. This case highlights that it is essential to carefully follow-up patients with Marfan syndrome after the Bentall operation.

Baroreflex Sensitivity in Patients With Atrial Fibrillation.

Background It has been reported that atrial fibrillation (AF) may contribute to impairment of baroreflex sensitivity (BRS). However, the difference of BRS between patients with persistent AF (PeAF) and those with paroxysmal AF (PAF) is unknown. We tested the hypothesis that patients with PeAF have a more impaired BRS compared with those with PAF. Methods and Results From October 2015 onwards, a total of 67 patients (14 women [20.9%]; mean age 65.2±10.1 years) with PAF (n=46, 68.7%) and PeAF (n=21, 31.3%), who underwent catheter ablation, were prospectively enrolled. The baseline BRS was evaluated during sinus rhythm. The baseline BRS in patients with PeAF was significantly lower than those with PAF (2.97 [0.52-6.62] ms/mm Hg versus 4.70 [2.36-8.37] ms/mm Hg, P=0.047). The BRS was significantly depressed after catheter ablation in all the patients (4.66 [1.80-7.37] ms/mm Hg versus 0.55 [-0.15 to 1.22] ms/mm Hg, P<0.001). However, the depression of BRS because of catheter ablation appeared attenuated in patients with PeAF when compared with those with PAF. The number of patients who did not show depression of BRS was significantly greater, that is, patients with PeAF (3/12, 25%) than those with PAF (0/46, 0%, P<0.01). Conclusions Our findings demonstrated that the baseline BRS was more depressed in patients with PeAF compared with PAF. Catheter ablation depressed BRS irrespective of the type of AF, with a greater effect in patients with PAF than PeAF.

Pseudoaneurysm of the Left Common Carotid Artery With Neurofibromatosis Type 1.

We describe a 54-year-old man with neurofibromatosis type 1 who presented with a left-sided neck mass. Computed tomography demonstrated a left common carotid artery aneurysm (51 × 33 mm). Surgery was performed because of the risk of rupture. The left common carotid artery was found to be a huge aneurysmal dilatation, and the arterial wall partially collapsed and extensively adherent to the surrounding tissues. Left common carotid artery to internal carotid artery bypass grafting was performed with a reversed saphenous vein graft. Histopathological examination revealed vascular fragility of the left carotid arterial wall.

[Combined Valvular Disease with Suspected Acquired von Willebrand Syndrome].

A 73-year-old female was referred to our department for surgical treatment of combined rheumatic valvular disease. She had undergone percutaneous transluminal mitral commissurotomy 29 years before. She underwent double valve replacement with bioprosthetic valves and tricuspid annuloplasty combined with left atrial appendectomy for chronic atrial fibrillation. Because of remarkable bleeding following surgery, rapid blood transfusion and re-thoracotomy were immediately performed. However, the bleeding persisted even after re-thoracotomy, and acquired von Willebrand syndrome due to valvular disease was suspected. Von Willebrand factor/factor Ⅷ preparation was administered, and bleeding promptly became under control. Recently, acquired von Willebrand syndrome due to valvular disease has attracted attention. We need to keep it in mind during perioperative management for patients with valvular disease.

Gorget-like Cuddling Suture: An Anastomosis Reinforcement Technique to Reduce Suture Bleeding for Aortic Surgery.

We developed a new reinforcement technique, the Gorget-like Cuddling (GOCU) suture, to prevent suture line bleeding during aortic surgery. After continuous aortic anastomosis with thick outer felt, an additional 2-0 Ticron (Medtronic, Minneapolis, MN) suture is placed distal from the first suture line. This GOCU suture directly holds the needle holes. Wall tension on the anastomosis can also be reduced to prevent longitudinal dilatation of the aorta. This technique can contribute to hemostasis for a fragile aortic wall in cases like acute aortic dissection.

Infected thoracic aortic aneurysm caused by Clostridium ramosum: A case report.

A 73-year-old man undergoing conservative management of acute aortic dissection (Stanford type B) was diagnosed with infected aortic aneurysm based on clinical findings of aortic dilatation and recurrent laryngeal nerve paralysis. We performed total aortic arch replacement with a synthetic graft and omentopexy; and Clostridium ramosum was isolated from resection specimens. Infected aortic aneurysms are rare but may lead to death from aortic dissection or rupture. C. ramosum infection is rare and has seldom been reported, and thus no treatment guidelines, including antibiotic therapy, have been established. Therefore, it is necessary to accumulate a larger number of cases of aortic aneurysm infected by C. ramosum. To date, there has been no reported case of infected aortic aneurysm due to C. ramosum. Here, we report a case of infected aortic aneurysm due to C. ramosum. .

Postoperative paraplegia after transapical transcatheter aortic valve implantation.

An 84-year-old man with severe aortic valve stenosis underwent transcatheter aortic valve implantation (TAVI). We selected a transapical approach TAVI because he had a 48-mm abdominal aortic aneurysm and his descending aorta was covered with severe atherosclerosis, a so-called "shaggy aorta". A 26-mm Sapien XT prosthesis (Edwards Lifesciences, Irvine, CA, USA) was successfully implanted, and TAVI was performed using cardiopulmonary bypass. His postoperative clinical course was unremarkable on the first day. On postoperative day 3, however, his systemic circulation suddenly collapsed due to cardiac tamponade. We performed an emergency re-thoracotomy. This operation improved his systemic circulation, but he had no movement in either leg. Magnetic resonance imaging showed spinal cord ischemia around the T10 level and acute multifocal micro cerebral infarctions. The cause of his neurological symptoms was thought to be spinal cord ischemia brought about by the shaggy aorta and low blood pressure due to cardiac tamponade after TAVI. .

Rupture of the Remaining Renal Artery Aneurysm While Waiting for Stage 2 Surgery for a Patient with Bilateral Renal Artery Aneurysms and Multiple Aneurysms.

A 21-year-old man was referred to our department for treatment of multiple aneurysms, including bilateral renal artery aneurysms. He was clinically diagnosed with Loeys-Dietz syndrome. So, we developed a 2-stage surgical strategy. The first surgery involved reconstructing the right renal artery and replacing part of the abdominal aorta, bilateral common iliac artery, and bilateral internal and external iliac arteries with a synthetic graft. Although stent grafting of the left renal artery aneurysm had been scheduled for the second surgery, sudden rupture of the left renal artery aneurysm forced us to perform emergency renal artery reconstruction.

Reconstruction of anomalous left coronary artery from pulmonary artery in an adult patient: a case report.

BACKGROUND: Anomalous left coronary artery from the pulmonary artery is a congenital heart disease in which myocardial ischemia occurs within 1 year of birth. Adults have been reported to survive owing to the development of collateral perfusion from right coronary artery. In these cases, however, revascularization is necessary to prevent sudden cardiac death. CASE PRESENTATION: A 62-year-old female gradually started experiencing dyspnea during exercise. Coronary computed tomography revealed that the left coronary artery arose from the main pulmonary artery. The patient was subsequently diagnosed with adult-type, anomalous left coronary artery from the pulmonary artery. She underwent a surgery, in which a 6-mm vascular prosthesis was passed through the main pulmonary artery to anastomose the left coronary artery and ascending aorta. CONCLUSION: Our reconstructive technique using vascular prosthesis is effective for anomalous left coronary artery from pulmonary artery in adults.

A case of ruptured aneurysm of coronary-pulmonary artery fistula diagnosed after emergency thoracotomy.

BACKGROUND: Coronary fistulae are occasionally detected using echocardiography or coronary angiography. We report a patient with cardiac tamponade because of a ruptured aneurysm of a coronary artery fistula. CASE PRESENTATION: A 60-year-old man was referred to our hospital with sudden onset of chest pain and unconsciousness. He was initially diagnosed with cardiac tamponade for type A acute aortic dissection, and an emergency operation was performed. A large amount of bleeding was seen in the pericardium, but aortic dissection around the arch was not observed. Instead, a ruptured aneurysm of a coronary-pulmonary fistula was identified on the pulmonary artery root. The aneurysm was resected, and the fistula was closed by ligation. The patient's postoperative progress was good, and he was discharged on postoperative day 12 without any abnormalities on the coronary arteriogram. CONCLUSIONS: Preoperative diagnosis of the rupture of the small coronary artery aneurysm is difficult in such an emergency case, and this possibility should be considered in differential diagnosis when the CT image does not show typical aortic dissection.

Therapeutic effect of lyophilized, Kefir-fermented milk on constipation among persons with mental and physical disabilities.

AIM: Constipation is a serious problem for persons with mental and physical disabilities in Japan. However, prophylaxis is extremely difficult because the major causes of constipation in these individuals are related to their mental and physical disabilities. Constipation can be successfully treated with glycerol enemas (GEs) and other aperients. As constipation is a lifetime issue for these persons, dietary regimens to prevent constipation can be important. METHODS: This study evaluated the probiotic effects of kefir-fermented milk for preventing constipation in 42 persons with mental and physical disabilities. The participants were administered 2 g of lyophilized kefir with each meal for 12 weeks and their bowel movements, the administration of GE and other aperients, and stool shape were recorded. RESULTS: The intake of kefir significantly reduced constipation, compared with the baseline status. Some individuals showed complete relief of constipation, whereas others showed no effect. CONCLUSION: Despite individual variations, consuming kefir daily could prevent constipation.

Perioperative management for iatrogenic aortocoronary dissection during percutaneous coronary intervention.

Aortocoronary dissection is a rare but serious complication. We report the case of a 72-year-old female with angina. Percutaneous coronary intervention was performed for right coronary artery disease. Manipulation of the guiding catheter led to aortocoronary dissection. A drug-eluting stent was immediately implanted in the right coronary ostium to seal the entry of the dissection. Computed tomography (CT) showed ascending aortic dissection. The patient was observed without surgery. CT performed the following day and showed the contrast in the false lumen which had disappeared. Clinicians are more likely to avoid surgical treatment if stenting successfully seals the entry of the coronary dissection.

Detection of DNA double-strand breaks by pulsed-field gel electrophoresis.

A DNA double-strand break (DSB) is one of the most cytotoxic DNA lesions because unrepaired DSBs cause chromosomal aberrations and cell death. Although many physiological DSBs occur at DNA replication sites, the molecular mechanisms underlying this remain poorly understood. There was therefore a need to develop a highly specific method to detect DSB fragments containing DNA replication sites. Here we investigated whether pulsed-field gel electrophoresis (PFGE) combined with visualization of DNA replication sites by immunoblotting using halogenized deoxyuridines, such as BrdU and IdU, was sufficient for this detection. Our methodology enabled us to reproduce previously reported data. In addition, this methodology was also applied to the detection of bacterial infection-induced DSBs on human chromosomal DNA. Based on our findings, we propose that this strategy combining PFGE with immunoblot analysis will be applicable to studies analyzing the mechanistic details of DNA repair, the DNA damage response and the activity of DNA-damaging agents.

[Transaortic Thoracic Endovascular Aortic Repair Via Right Anterior Mini-thoracotomy;Report of a Case].

An 81-year-old man presented with ruptured thoracic aortic aneurysm under stable condition. He had been suffering from chronic obstructive pulmonary disease, chronic renal failure and rheumatoid arthritis. We performed hybrid thoracic endovascular aortic repair via right anterior mini-thoracotomy inserting a device through a conduit on the ascending aorta. The patient was discharged without aorta-related complications.

Unique Technique for Open Surgical Repair after Failed Endovascular Aneurysm Repair with Proximal Anastomoses.

Endovascular aortic aneurysm repair (EVAR) has revolutionized the management of abdominal aortic aneurysms (AAAs), with lower perioperative morbidity and mortality compared to conventional surgical repair. However, late secondary re-interventions after EVAR are still needed before aneurysm rupture in many cases. A patient with impending rupture of an AAA associated with a type I endoleak 7 years after EVAR who was successfully treated with a unique technique of fixation of the proximal aortic neck taking into account the structure of the stent graft is reported. This technique offers a safe solution to late open conversion after failed EVAR.