Fibrin Hydrogel Layer-Anchored Pericardial Matrix Prevents Epicardial Adhesion in the Severe Heart Adhesion-Induced Miniature Pig Model.

Postoperative adhesion is a very common and serious complication that occurs frequently in cardiac surgery. The purpose of this study was to evaluate the efficacy of a fibrin hydrogel layer-anchored decellularized pericardial matrix in preventing pericardial adhesions in a miniature pig model with a myocardial injury. Fibrin hydrogel layer-anchored decellularized pericardial matrix was prepared by spraying a mixture of fibrinogen and thrombin on a fibrinogen-doped decellularized pericardium. Cardiac injury was generated by abrading and desiccating the epicardial surface of a miniature pig to induce severe postoperative adhesions. The adhesion between the epicardial surface and fibrin hydrogel layer-anchored decellularized pericardial matrix in three different regions (left outer, front, and right outer) was evaluated macroscopically one month after surgery. The fibrin hydrogel layer-anchored decellularized pericardial matrix showed significantly less adhesion than an autologous pericardium (0.2 ± 0.7 in DPM-FHG0.5 and 0.4 ± 0.8 in DPM-FHG1, p < 0.01) and expanded polytetrafluoroethylene (ePTFE) (1.6 ± 0.5, p < 0.05). The fibrin hydrogel concentration had no effect on preventing postoperative adhesion. A thinner fibrin hydrogel layer was observed on the decellularized pericardial matrix one month after surgery; however, the inside of the matrix was filled with fibrin hydrogel. Fibrin hydrogel layer-anchored decellularized pericardial matrix prevented postoperative epicardial adhesions in a miniature pig model. Our findings suggest that pericardial closure using a fibrin hydrogel layer-anchored decellularized pericardial matrix is a promising method for preventing adverse outcomes in reoperative surgeries.

4-Arm PEG-Functionalized Decellularized Pericardium for Effective Prevention of Postoperative Adhesion in Cardiac Surgery.

Postoperative adhesions are a very common and serious complication in cardiac surgery, and the development of an effective anti-adhesion membrane showing resistance to the physical stimulus generated by the pulsation of the heart is desirable. In this study, an anti-adhesion material was developed through amine coupling between decellularized bovine pericardia (dBPCs) and 4-arm poly(ethylene glycol) succinimidyl glutarate (4-arm PEG-NHS) for the postoperative care of cardiac surgical patients. The efficacy of the 4-arm PEG-functionalized dBPCs in the prevention of adhesions after cardiac surgery was investigated in a rabbit heart adhesion model. The dBPCs meet the requirements for biocompatibility, flexibility, and sufficient suturable strength, and the 4-arm PEG moieties provide an anti-adhesion effect by the high excluded volume interactions of the PEG chains with proteins. The 4-arm PEG-functionalized dBPCs had a significantly greater anti-adhesion effect than the other materials tested and showed re-establishment of the mesothelial monolayer. These results suggested that the 4-arm PEG-functionalized dBPCs are a favorable material for an anti-adhesion membrane.

In vivo recellularization of xenogeneic vascular grafts decellularized with high hydrostatic pressure method in a porcine carotid arterial interpose model.

Autologous vascular grafts are widely used in revascularization surgeries for small caliber targets. However, the availability of autologous conduits might be limited due to prior surgeries or the quality of vessels. Xenogeneic decellularized vascular grafts from animals can potentially be a substitute of autologous vascular grafts. Decellularization with high hydrostatic pressure (HHP) is reported to highly preserve extracellular matrix (ECM), creating feasible conditions for recellularization and vascular remodeling after implantation. In the present study, we conducted xenogeneic implantation of HHP-decellularized bovine vascular grafts from dorsalis pedis arteries to porcine carotid arteries and posteriorly evaluated graft patency, ECM preservation and recellularization. Avoiding damage of the luminal surface of the grafts from drying significantly during the surgical procedure increased the graft patency at 4 weeks after implantation (P = 0.0079). After the technical improvement, all grafts (N = 5) were patent with mild stenosis due to intimal hyperplasia at 4 weeks after implantation. Neither aneurysmal change nor massive thrombosis was observed, even without administration of anticoagulants nor anti-platelet agents. Elastica van Gieson and Sirius-red stainings revealed fair preservation of ECM proteins including elastin and collagen after implantation. The luminal surface of the grafts were thoroughly covered with von Willebrand factor-positive endothelium. Scanning electron microscopy of the luminal surface of implanted grafts exhibited a cobblestone-like endothelial cell layer which is similar to native vascular endothelium. Recellularization of the tunica media with alpha-smooth muscle actin-positive smooth muscle cells was partly observed. Thus, we confirmed that HHP-decellularized grafts are feasible for xenogeneic implantation accompanied by recellularization by recipient cells.

[Rabbit Model for Evaluation of Anti-adhesive Materials after Open Heart Surgery].

Surgical trauma to the pericardial mesothelium during open heart procedures has formation of fibrovascular adhesions. Surgeons are confronted with cardiac adhesions, leading to an increased surgical risk such as intractable bleeding and possible catastrophic hemorrhage. In order to solve the problem, the anti-adhesion membrane has been developed and used. However, their performances are far from perfect, so it has been expected to develop a novel anti-adhesive material. For preparing an anti-adhesive material, there is 1 serious problem, a lack of golden standard of animal model for evaluation of anti-adhesivity. In this study, we tried to establish a standard system for evaluation of the performance of anti-adhesive materials for the chest-area surgery using rabbit. Setting the condition of the damage to heart, the objective evaluation system was established. And we performed experimental study to evaluate prevention of adhesions with pericardial substitutes and our product under development based on this model.

Evaluation of small-diameter vascular grafts reconstructed from decellularized aorta sheets.

Following small-diameter vascular grafting, blood vessels fail to retain excellent antithrombotic function and therefore require application of antithrombogenic drugs. We have previously reported early attachment of endothelial cells to the luminal surface of high hydrostatic pressure (HHP)-decellularized arteries after transplantation. In addition, the graft retained antithrombotic function by endothelialization and remained open for several weeks. To fabricate tube grafts of optimal size and shape for small-diameter vascular grafting, we evaluated decellularized porcine aorta sheets as a suitable antithrombogenic material. Porcine aortic sheets were decellularized using detergent-based or HHP methods. The HHP-, but not detergent-based-, decellularized aortic sheets were verified to be acellular, and the mechanical properties of the native aortic sheet remained intact. To fabricate vascular grafts, the decellularized aortic sheets were rolled into tubes and secured using fibrin glue bonding. After implantation into a rat carotid artery model, the tubular grafts withstood normal blood pressure, mechanical beating, and pulsatile flow. After 3 weeks, the tubular grafts remained patent and recipient cell infiltration and cell attachment were observed on the luminal surface. These results indicate that HHP-decellularized aortic sheets may be useful as an antithrombogenic material for tubular vascular grafts. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1293-1298, 2017.

Histological structure affects recellularization of decellularized arteries.

Decellularized arteries were prepared to evaluate the in vivo recellularization of biological material after implantation. Porcine aortas and radial arteries were decellularized using high-hydrostatic pressure to form materials with histologically-different structures. Successful removal of cells from decellularized arteries was evaluated by hematoxylin-eosin staining and measurement of residual DNA. Cell remnants were eliminated completely from the decellularized arteries, and histological structures were preserved. Cells adhered to all decellularized artery samples, but infiltration of cells was observed only from the adventitial side of the decellularized radial artery. Rats were implanted subcutaneously with a decellularized aorta or radial artery to evaluate in vivo performance. Decellularized aortic tissue prevented cell infiltration better than that of the decellularized radial artery, suggesting that the elastin lamina in decellularized tissues prevents cell infiltration and suppresses recellularization.

[New Intracoronary Shunt Cannula in Off-pump Coronary Artery Bypass Grafting].

In off-pump coronary artery bypass grafting(OPCAB), a bloodless operative field has great influence on the quality of anastomosis. In addition, maintenance of distal coronary flow during anastomosis stabilizes hemodynamics. We introduced a new intracoronary shunt cannula, Mini Shunt Pro (MSP). MSP adopts the step-tip, which allows easy insertion and reduces the risk of intimal injury. The distal and proximal sides of the tips of MSP are 0.25 mm different in diameter, which improves its fitness to the coronary artery and enhances a bloodless operative field. This new shunt cannula is considered to be safe and useful for high-quality anastomosis in OPCAB.

Effect of decellularized tissue powders on a rat model of acute myocardial infarction.

Many research groups are currently investigating new treatment modalities for myocardial infarction. Numerous aspects need to be considered for the clinical application of these therapies, such as low cell integration and engraftment rates of cell injection techniques. Decellularized tissues are considered good materials for promoting regeneration of traumatic tissues. The properties of the decellularized tissues are sustained after processing to powder form. In this study, we examined the use of decellularized tissue powder in a rat model of acute myocardial infarction. The decellularized tissue powders, especially liver powder, promoted cell integration and neovascularization both in vitro and in vivo. Decellularized liver powder induced neovascularization in the infarct area, resulting in the suppression of myocardial necrosis. The results of this study suggest that decellularized liver powder has good potential for application as a blood supply material for the treatment of myocardial infarction.

[An ascending graft replacement surgery in acute aortic dissection with preoperative cerebral infarction responding to postoperative external and internal decompression; report of a case].

We report a case of a 71-year-old woman who had extensive cerebral infarction associated with acute type A aortic dissection. We urgently performed ascending aortic graft replacement. Postoperative computed tomography of the brain taken immediately after the aortic surgery showed further aggravation of the right cerebral edema and a midline shift. The patient underwent emergent internal and external decompression of the brain. Eventually, consciousness recovered to normal level though preoperative left paraplegia persisted. She was discharged 150 days after the operation. We conclude that immediate internal and external cerebral decompression after surgery for acute type A dissection with preoperative cerebral malperfusion can prevent postoperative higher brain dysfunction.

Repeat conduit replacement in the pulmonary position without sternal resplitting for the patient with repaired Tetralogy of Fallot and the absent inferior caval vein.

Recently, sternal reentry has been performed with low perioperative mortality and morbidity. In some patients, however, there are specific problems leading to life-threatening events during sternal reentry. A 27-year-old woman with repaired Tetralogy of Fallot and the absent inferior caval vein was referred to our department for pulmonary conduit replacement. Preoperative computed tomography disclosed the dominant right coronary artery and the ascending aorta longitudinally running just beneath the midline of the sternum. Therefore, we selected bilateral antero-lateral thoracotomy as the alternative approach to avoid the injury of these vital organs. The left axillar and right femoral artery were used for arterial perfusion sites. Venous drainage could be obtained from the left superior caval vein and the isolated hepatic vein via the left antero-lateral thoracotomy, and the right superior caval vein via the right antero-lateral thoracotomy. We successfully performed the repeat conduit replacement via the right antero-lateral thoracotomy.

Endovascular stent-grafting of anastomotic pseudoaneurysms following thoracic aortic surgery.

PURPOSE: Anastomotic pseudoaneurysm is a rare but life-threatening complication after thoracic aortic surgery. Endovascular stent-grafting is a less invasive treatment for thoracic aortic aneurysm; however, its clinical usefulness for anastomotic pseudoaneurysms following thoracic aortic surgery is unclear. METHODS: A series of 12 anastomotic pseudoaneurysms in 10 patients, which occurred following thoracic aortic surgery, underwent endovascular stent-grafting in our university hospital. Eight emergent endovascular stent-grafting cases were included in this study. A hand-made stent-graft, reconstructed by suturing graft material to an endoskeleton of modified Gianturco Z stents, was used in all cases. RESULTS: The delivery success rate was 91.7%, and the hospital mortality rate was 25.0%. Two cases were converted to open surgery during the postoperative phase because of a type I endoleak. Complete absorption or shrinkage of the anastomotic pseudoaneurysm was observed in seven of nine cases. CONCLUSION: Endovascular stent-grafting for patients with anastomotic pseudoaneurysms of the thoracic aorta following thoracic aortic surgery has become a possible optimal treatment. However, long-term outcome remains unclear, and periodical follow-up is required.