Reduction of perioperative blood loss and operating time for arthroscopic rotator cuff repair by intravenous administration of tranexamic acid.

Background: Tranexamic acid (TXA) is widely used in hip and knee arthroplasty to reduce perioperative bleeding. Recently, its use has been expanded to arthroscopic surgery. The purpose of this study was to evaluate the efficacy of preoperative use of TXA in arthroscopic rotator cuff repair (RCR). Methods: A cohort comprising 129 consecutive patients who underwent arthroscopic primary RCR at our institution was retrospectively investigated according to whether they received TXA (April 2018 to December 2020, TXA group, n = 64) or did not receive TXA (April 2016 to March 2018, non-TXA group, n = 65). TXA was administered at a dose of 1 g intravenously. Rotator cuff tears were repaired by the suture bridge technique. Videos of the arthroscopic procedures were reviewed and rated for visual clarity using a 10-point numeric rating scale. Arthroscopic procedures were divided into glenohumeral, resection of bursal tissue and acromioplasty, and RCR steps. Each step was rated separately. Age, sex, body mass index, hemoglobin level before and on days 1 and 7 after surgery, operating time, mean arterial pressure, tear size, and number of anchors used for cuff repair were compared between the two groups. Results: There were no statistically significant differences in the patient demographic data. The operating time was significantly shorter in the TXA group than in non-TXA group (97.8 ± 21.8 min vs 116.2 ± 26.0 min). The clarity of the visual field was similar between the two groups during the glenohumeral phase but was significantly higher in the TXA group during the resection of bursal tissue and acromioplasty and RCR phases. Hemoglobin level was not significantly different between the groups on postoperative day 1 but was significantly higher in the TXA group on day 7. Conclusion: Administration of a single intravenous dose of TXA improved visual clarity in arthroscopic RCR, decreased the total operating time, and reduced hemoglobin loss on postoperative day 7.

Blue light induces apoptosis and autophagy by promoting ROS-mediated mitochondrial dysfunction in synovial sarcoma.

BACKGROUND: Synovial sarcoma (SS) has limited treatment options and there is an urgent need to develop a novel therapeutic strategy to treat SS. Blue light (BL) has been shown to inhibit the growth of several cancer cells. However, the efficacy of BL in soft tissue sarcomas such as SS has not been demonstrated, and the detailed mechanism underlying the antitumor activity of BL is not fully understood. In this study, we investigated the antitumor effect of BL on SS. METHODS: Human SS cell lines were continuously irradiated with BL using light-emitting diodes (LEDs) in an incubator for in vitro analysis. The chicken chorioallantoic membrane (CAM) tumors and xenograft tumors in mice were subjected to daily BL irradiation with LEDs. RESULTS: BL caused growth inhibition of SS cells and histological changes in CAM tumors. BL also suppressed the migration and invasion abilities of SS cells. The type of cell death in SS cells was revealed to be apoptosis. Furthermore, BL induced excessive production of reactive oxygen species (ROS) in mitochondria, resulting in oxidative stress and malfunctioned mitochondria. Reducing the production of ROS using N-acetylcysteine (NAC), a ROS scavenger, attenuated the inhibitory effect of BL on SS cells and mitochondrial dysfunction. In addition, BL induced autophagy, which was suppressed by the administration of NAC. The autophagy inhibitor of 3-methyladenine and small interfering RNA against the autophagy marker light chain 3B facilitated apoptotic cell death. Moreover, BL suppressed tumor growth in a mouse xenograft model. CONCLUSION: Taken together, our results revealed that BL induced apoptosis via the ROS-mitochondrial signaling pathway, and autophagy was activated in response to the production of ROS, which protected SS cells from apoptosis. Therefore, BL is a promising candidate for the development of an antitumor therapeutic strategy targeting SS.

Insufficient Recovery From C5 Palsy Following Anterior Cervical Decompression and Fusion.

STUDY DESIGN: Retrospective study. OBJECTIVE: To determine the risk factors for insufficient recovery from C5 palsy (C5P) following anterior cervical decompression and fusion (ADF). SUMMARY OF BACKGROUND DATA: Postoperative C5P is a frequent but unsolved complication following cervical decompression surgery. Although most patients gradually recover, some recover only partially. When we encounter new-onset C5P following ADF, the question that often arises is whether the palsy will sufficiently resolve. METHODS: We retrospectively reviewed consecutive patients who underwent ADF at our institution. We defined C5P as postoperative deterioration of deltoid muscle strength by two or more grades determined by manual muscle testing (MMT). We evaluated the following demographic data: patient factors, surgical factors, and radiological findings. C5P patients were divided into two groups: sufficient recovery (MMT grade≧4) and insufficient recovery (MMT grade < 4). Each parameter was compared between the two groups. RESULTS: Of 839 patients initially included in the study, 57 experienced new-onset C5P (6.8%). At the final follow-up (mean, 55 ±â€Š17 months), 41 patients experienced sufficient recovery, whereas 16 (28%) still exhibited insufficient recovery. Compared with the sufficient recovery group, patients with insufficient recovery exhibited a higher decompression combination score, a larger anterior shift in preoperative cervical sagittal balance, less lordosis of the pre- and postoperative C4/C5 segment, more frequent stenosis at the C3/C4 segment, lower deltoid strength at C5P onset, more frequent co-occurrence of biceps weakness, greater postoperative expansion of the dura mater, and more frequent presence of postoperative T2 high-intensity areas. Multivariate analysis revealed that co-occurrence of biceps muscle weakness, less lordosis at the preoperative C4/C5 segment, and postoperative expansion of the dura mater were independent predictors of insufficient recovery. CONCLUSION: The combination of unfavorable conditions, such as potential spinal cord disorder, cervical malalignment, and excessive expansion of the dura mater after corpectomy, predicts insufficient recovery from C5P.Level of Evidence: 4.

Partial thickness tear of the supraspinatus at the musculotendinous junction in a softball catcher.

We report a rare case of a partial thickness tear of the supraspinatus at the musculotendinous junction in a softball catcher. Preoperative magnetic resonance images of the shoulder showed high signal intensity areas at the musculotendinous junction, along with discontinuity of the articular side of the supraspinatus. Arthroscopic examination revealed articular-side partial tear at the musculotendinous junction. The patient was able to return to playing softball 20 weeks after arthroscopic side-to-side repair. J. Med. Invest. 68 : 386-388, August, 2021.

Intramyocardial Transplantation of Human iPS Cell-Derived Cardiac Spheroids Improves Cardiac Function in Heart Failure Animals.

The severe shortage of donor hearts hampered the cardiac transplantation to patients with advanced heart failure. Therefore, cardiac regenerative therapies are eagerly awaited as a substitution. Human induced pluripotent stem cells (hiPSCs) are realistic cell source for regenerative cardiomyocytes. The hiPSC-derived cardiomyocytes are highly expected to help the recovery of heart. Avoidance of teratoma formation and large-scale culture of cardiomyocytes are definitely necessary for clinical setting. The combination of pure cardiac spheroids and gelatin hydrogel succeeded to recover reduced ejection fraction. The feasible transplantation strategy including transplantation device for regenerative cardiomyocytes are established in this study.

Association Between C5 Palsy and the Anterior Decompression Procedures, Corpectomy and Discectomy.

STUDY DESIGN: This is a retrospective study. OBJECTIVE: The aim was to evaluate the influence of various decompression procedures on the incidence of C5 palsy (C5P). SUMMARY OF BACKGROUND DATA: C5P is a well-known but unsolved complication of cervical spine surgery. Among anterior cervical decompressive procedures, both corpectomy and discectomy are important surgical methods, whose effects on the incidence of C5P are unknown. METHODS: We retrospectively analyzed 818 patients (529 men; mean age: 59.2±11.6 y) who underwent anterior cervical decompression and fusion. The surgical choice to use corpectomy, discectomy, or hybrid decompression was based on standard treatment strategies depending on local compressive pathology and presenting clinical symptoms. We introduced an original "decompression combination score" as a means of quantifying the effects of the procedures on the development of C5P. The scores were based on the relative severity of various risk factors associated with the eventual development of C5P and were assigned as follows: C4 corpectomy, 1 point; C5 corpectomy, 1 point; C3 corpectomy successive to C4 corpectomy, 0.5 point; C6 or C7 corpectomy successive to C5 corpectomy, 0.5 point; C4/5 discectomy, 0.5 point; discectomy at another segment, 0 point. Each patient's decompression combination score was then comprised of the sum of these points. RESULTS: C5P occurred in 55 (47 men, mean age: 65.7±8.7 y) of the 818 (6.7%) patients. A larger number of operated disc segments was significantly associated with C5P. Higher decompression combination score was significantly associated with C5P. Multivariate analysis revealed that male sex, higher decompression combination score, and older age were significant risk factors. CONCLUSIONS: Corpectomy increased the incidence of C5P, while discectomy decreased the risk. The lower incidence of postoperative C5P after discectomy may be because of minimizing tethering effect to the C5 nerve root. As a preventive measure against C5P, corpectomy should be avoided, while discectomy is recommended as much as possible. LEVEL OF EVIDENCE: Levels of Evidence: Step IV-Oxford Center for Evidence-Based Medicine 2011.

[Cardiac Surgery for Mitral Regurgitation Associated with Essential Thrombocythemia].

An 80-year-old woman with essential thrombocythemia was diagnosed with severe mitral regurgitation and moderate tricuspid regurgitation. Preoperatively, she had been treated with hydroxycarbamide and low-dose aspirin since her platelet count was high( 96.2×104/µl). After the platelet count was reduced to 46.2×104/µl, she underwent mitral valve repair and tricuspid valve annuloplasty. Atypical heparin resistance was noted intraoperatively. After initial heparin infusion, the activated clotting time(ACT) increased as expected. However, it decreased after initiation of cardiopulmonary bypass, despite additional heparin infusion and heparin concentration maintenance. A correlation between platelet factor 4 and heparin resistance was suggested. On discharge, she had no complications. We should consider the possibility of heparin resistance in essential thrombocythemia even when platelet count is adequately controlled.

Quadricuspid aortic valve repair by neo-cuspidization of an accessory cusp using autologous pericardium.

We present a successful case of the management of a 46-year-old woman with an abnormal aortic valve formed by four cusps (three equal large cusps and one smaller cusp; type B according to the Hurwitz and Roberts classification) with a marked loss of coaptation that caused a severe aortic insufficiency (AI). The patient underwent an aortic valvuloplasty of the defect using the glutaraldehyde (GA)-pretreated autologous pericardium, restoring the subnormal function and competency of the aortic valve. The postoperative course was unremarkable. The early follow-up showed a trivial AI and a significant reduction of regurgitant volume was identified in a cardiac magnetic resonance imaging (MRI) when compared to the preoperative state (27.2 vs. 2.1 ml). The follow-up transthoracic echocardiography 1 year after the surgery showed mild AI.

Preoperative Planning for Physician-Modified Endografts Using a Three-Dimensional Printer.

The medical uses of three-dimensional (3D) printing are evolving at a rapid pace. The current roles and the future outlooks of this technology for physician-modified endovascular graft (PMEG) in patients with juxtarenal aneurysm are discussed. Fenestrations of PMEG are designed taking into account the geometry of the stent graft. Designing of such stent grafts is extremely complicated, especially when PMEG is planned for the angulated portion of the aorta. A 3D model enables the designing of branch fenestrations, with consideration for the geometrical adaptation of the stent graft in a complex aortic anatomy. With the aid of 3D-printing technology, patients with juxtarenal aortic pathologies can be treated using fenestrated stent grafts, preserving the vital organ circulation and securing a robust length of proximal sealing zone.

One Technique to Modulate a Device Implantation Path in a Short Treatment Length Using the Gore IBE Device.

The GORE EXCLUDER Iliac Branch Endoprosthesis (IBE; W. L. Gore and Associates, Flagstaff, AZ, USA) applicability is limited by the aorto-iliac length (AOL). The shortage may be a major exclusion criterion. An 85-year-old male presented with an abdominal aortic and left common iliac arterial aneurysm. The left-side AOL was 146-mm, which was deemed 19-mm too short for IBE usage. To increase implantation length, the contra-lateral connection stent graft was deployed along the implantation line, wound half-circumferentially around the ipsilateral limb. Any form of endoleak, limb occlusion, and device migration has not been observed for twelve months.

[Aortic Valve-preserving Root Remodeling in a Patient with Bicuspid Aortic Valve and Severe Annulo-aortic Ectasia].

A 48-year-old man underwent aortic root remodeling for a giant aneurysm of sinus of Valsalva, 98 mm in diameter, as well as a bicuspid aortic valve. The aortic valve was defined as type 0(L-R) according to Sievers classification and the aortic annulus was highly dilated up to 35 mm. Geometric height of the left and right cusps were 22 mm and 32 mm in diameter, respectively. Dacron straight graft of 24 mm was chosen and each tongue was then created in a 180°fashion. After completion of root reconstruction, external circular suture annuloplasty using CV-0 expanded polytetrafluoroethylene (ePTFE) was made to adjust the annulus down to 22 mm in diameter. The free margin of both cusps were centrally plicated to raise the effective height to 9 mm. Postoperative echocardiography at 2 year showed trivial aortic regurgitation but no root re-dilatation. Remodeling with external circular suture annuloplasty is a reproducible and reliable method to stabilize the root, even for the patient with a giant aneurysm of sinus of Valsalva.

Development of a transplant injection device for optimal distribution and retention of human induced pluripotent stem cell‒derived cardiomyocytes.

BACKGROUND: Induced pluripotent stem cell (iPSC)‒based regenerative therapy is a promising strategy for cardiovascular disease treatment; however, the method is limited by the myocardial retention of grafted iPSCs. Thus, an injection protocol that efficiently introduces and retains human iPSC-derived cardiomyocytes (hiPSC-CMs) within the myocardium is urgently needed. The objective of the present study was to develop a method to improve the retention of hiPSCs in the myocardium for cardiac therapy. METHODS: We efficiently produced hiPSC-CM spheroids in 3-dimensional (3D) culture using microwell plates, and developed an injection device for optimal 3D distribution of the spheroids in the myocardial layer. Device biocompatibility was assessed with purified hiPSC-CM spheroids. Device effectiveness was evaluated in 10- to 15-month-old farm pigs (n = 15) and 5- to 24-month-old micro-minipigs (n = 20). The pigs were euthanized after injection, and tissues were harvested for retention and histologic analysis. RESULTS: We demonstrated an injection device for direct intramyocardial transplantation of hiPSC-CM spheroids from large-scale culture. The device had no detrimental effects on cell viability, spheroid shape, or size. Direct epicardial injection of spheroids mixed with gelatin hydrogel into beating porcine hearts using this device resulted in better distribution and retention of transplanted spheroids in a layer within the myocardium than did conventional needle injection procedures. CONCLUSIONS: The combination of the newly developed transplant device and spheroid formation promotes the retention of transplanted CMs. These findings support the clinical application of hiPSC-CM spheroid‒based cardiac regenerative therapy in patients with heart failure.

Surgical strategies and outcomes for intradural lipomas over the past 20 years.

Intradural lipoma is an extremely rare spinal tumor. The boundary between the spinal cord and the lipoma is usually unclear, with adhesions being firm. Thus, total resection of the tumor is difficult and the neurological prognosis after total resection is poor. Information on the management of this type of tumor is scarce owing to the limited studies that have been conducted and the low sample sizes reported. Here, we report a case and provide a review of the literature on intradural lipomas over the past 20 years. In addition to describing our case, we reviewed reports published in Pubmed and CiNii. The demographic data of the patients included in these studies were extracted and the surgical procedures were assessed, along with their corresponding postoperative outcomes. There were 57 primary cases and 4 cases of recurrence. Among the primary cases, the neurological symptoms were persistent in 54 (95%) after surgery. The postoperative outcomes after excessive (>60% tumor resection) or total resection were significantly poor. In the recurrence cases, the mean period from initial surgery to recurrence was 11 years and all initial surgical procedures involved only partial resection surgery. This report is, to the best of our knowledge, the most exhaustive analysis of cases of intradural lipomas and recurrences. The optimal treatment for lipoma necessitates both partial resection and duraplasty.

Efficient Large-Scale 2D Culture System for Human Induced Pluripotent Stem Cells and Differentiated Cardiomyocytes.

Cardiac regenerative therapies utilizing human induced pluripotent stem cells (hiPSCs) are hampered by ineffective large-scale culture. hiPSCs were cultured in multilayer culture plates (CPs) with active gas ventilation (AGV), resulting in stable proliferation and pluripotency. Seeding of 1 × 106 hiPSCs per layer yielded 7.2 × 108 hiPSCs in 4-layer CPs and 1.7 × 109 hiPSCs in 10-layer CPs with pluripotency. hiPSCs were sequentially differentiated into cardiomyocytes (CMs) in a two-dimensional (2D) differentiation protocol. The efficiency of cardiac differentiation using 10-layer CPs with AGV was 66%-87%. Approximately 6.2-7.0 × 108 cells (4-layer) and 1.5-2.8 × 109 cells (10-layer) were obtained with AGV. After metabolic purification with glucose- and glutamine-depleted and lactate-supplemented media, a massive amount of purified CMs was prepared. Here, we present a scalable 2D culture system using multilayer CPs with AGV for hiPSC-derived CMs, which will facilitate clinical applications for severe heart failure in the near future.

Anatomic Feasibility of Next-Generation Stent Grafts for the Management of Type A Aortic Dissection in Japanese Patients.

BACKGROUND: The aims of the present study were to analyze the anatomical characteristics of type A aortic dissections (TAAD) in Japanese patients and evaluate the feasibility of 3 next-generation stent grafts dedicated to ascending/arch aortic lesions.Methods and Results:We analyzed 172 consecutive patients surgically treated for TAAD at 2 institutions between 2007 and 2015. Computed tomography (CT) images and operative records were used to identify the location of entry tear (ET). The anatomical feasibility of the Zenith Ascend, Zenith A-branch, and TAG Thoracic Branch Endoprosthesis (TBE) was evaluated using the manufacturers' instructions for use (IFU). In total, 131 patients were included in the final analysis. Dissection was present at the sinotubular junction (STJ) in 107 patients (81.7%), and the mean diameter of the STJ was 39.4±6.0 mm. The ET was at the STJ (n=33), ascending aorta (n=47), aortic arch (n=30), and descending aorta (n=21). The mean lengths from STJ to innominate artery and STJ to ET were 79.5±11.4 mm and 57.8±52.1 mm, respectively. When we applied the IFU to each anatomical measurement, we identified 0 patients as candidates for Zenith Ascend, 9 (6.9%) for Zenith A-branch, and 60 (45.8%) for TAG TBE. CONCLUSIONS: Endovascular treatment for TAAD was not feasible for most of this study population, with risk of stent graft-induced new entry in 81.7% of patients, despite the use of next-generation stent grafts.

Surgical results and complications of anterior decompression and fusion as a revision surgery after initial posterior surgery for cervical myelopathy due to ossification of the posterior longitudinal ligament.

OBJECTIVE Ossification of the posterior longitudinal ligament (OPLL) is a progressive disease. An anterior cervical decompression and fusion (ACDF) procedure for cervical OPLL is theoretically feasible, as the lesion exists anteriorly; however, such a procedure is considered technically demanding and is associated with serious complications. Cervical laminoplasty is reportedly an effective alternative procedure with few complications; it is recognized as a comparatively safe procedure, and has been widely used as an initial surgery for cervical OPLL. After posterior surgery, some patients require revision surgery because of late neurological deterioration due to kyphotic changes in cervical alignment or OPLL progression. Here, the authors retrospectively investigated the surgical results and complications of revision ACDF after initial posterior surgery for OPLL. METHODS This was a single-center, retrospective study. Between 2006 and 2013, 19 consecutive patients with cervical OPLL who underwent revision ACDF at the authors' institution after initial posterior surgery were evaluated. The mean age at the time of revision ACDF was 66 ± 7 years (± SD; range 53-78 years). The mean interval between initial posterior surgery and revision ACDF was 63 ± 53 months (range 3-235 months). RESULTS The mean follow-up period after revision ACDF was 41 ± 26 months (range 24-108 months). Before revision ACDF, the mean maximum thickness of the ossified posterior longitudinal ligament was 7.2 ± 1.5 mm (range 5-10 mm), and the mean C2-7 angle was 1.3° ± 14° (range -40° to 24°). The K-line was plus (OPLL did not exceed the K-line) in 8 patients and minus in 11 (OPLL exceeded the K-line). The mean Japanese Orthopaedic Association score improved from 10 ± 3 (range 3-15) before revision ACDF to 11 ± 4 (range 4-15) at the last follow-up, and the mean improvement rate was 18% ± 18% (range 0%-60%). A total of 16 surgery-related complications developed in 12 patients (63%). The main complication was an intraoperative CSF leak in 8 patients (42%). Neurological function worsened in 5 patients (26%). The deterioration was due to spinal cord herniation through a defective dura mater in 1 patient, unidentified in 1 patient, and C-5 palsy that gradually recovered in 3 patients. Reintubation, delirium, and hoarseness were observed in 1 patient each (5%). No patient required reoperation for reconstruction failure, and all patients eventually had a solid bony fusion. CONCLUSIONS ACDF as revision surgery after initial posterior surgery for cervical myelopathy due to OPLL is associated with a high incidence of intraoperative CSF leakage and an extremely low improvement rate. The authors think that while the use of revision ACDF must be limited, it is indispensable in special cases, such as progressing myelopathy following posterior surgery due to a very large beak-type OPLL that exceeds the K-line. Postoperative OPLL progression and/or kyphotic changes can possibly cause later neurological deterioration. Fusion should be recommended at the initial surgery for many cases of cervical OPLL to prevent such a challenging revision surgery.

Postoperative Stroke after Debranching with Thoracic Endovascular Aortic Repair.

OBJECTIVES: This study aimed to analyze the perioperative stroke rate, stroke lesions, outcome, risk factors, and stroke prevention following debranching with thoracic endovascular aortic repair (TEVAR). DESIGN: Retrospective study. METHODS: Between February 2011 and February 2015, 74 consecutive patients underwent debranching with TEVAR at our institution. Of these, the TEVAR proximal landing zone was "zone 0" in 23 patients, "zone 1" in 28, and "zone 2" in 23. Left subclavian artery (LSA) occlusion with coil embolization, balloon occlusion, or vascular plugging was performed in 27 patients. Mean follow-up time was 19.2 months (range 2-52 months). RESULTS: The in-hospital mortality rate was 4.1%. Stroke developed in 7 patients (9.5%), zone 0 in 4 patients, zone 1 in 2, and zone 2 in 1. Six of these patients had stroke lesions arising from the vertebral/basilar artery. Univariate analysis revealed a significant increase in the risk of postoperative stroke in patients with intraluminal atheroma (P = 0.001), those who underwent prior percutaneous transluminal coronary angioplasty or coronary artery bypass graft (P = 0.002), and those with a long operative duration (P = 0.001). Additionally, LSA occlusion significantly decreased the incidence of stroke (P = 0.041). The postsurgical 1- and 2-year cumulative survival rates were 87.3% and 77.0%, respectively, in those without stroke, and 68.6% and 22.9%, respectively, in those with stroke (P = 0.012). CONCLUSIONS: Stroke after debranching with TEVAR was associated with a high mortality. To prevent stroke, careful patient selection and protection of the vertebral artery are important. Prophylactic LSA occlusion at the time of stent-graft deployment might reduce the risk of perioperative stroke.

[Myocardial Ischemia in Acute Type A Aortic Dissection; Coronary Artery Dissection and Functional Ischemia].

Myocardial ischemia due to acute type A dissection is a fatal complication. This study was undertaken to evaluate the surgical results of acute type A aortic dissection with myocardial ischemia. Between 1986 and 2014, 364 patients were treated for acute type A dissection in our hospital. Twenty-four patients were underwent myocardial revascularization. Preoperative coronary artery stent placement was involved in 2, coronary-artery bypass grafting (CABG) 18 (right 12, left 4, both 2), reCABG 2, and Carrel patch with coronary orifice restoration 2. Seven of CABG group had no symptom of myocardial ischemia, but right coronary artery was circumferentially detached from the intimal ostia. Hospital mortality was 20.1% in patients who underwent CABG. Sixteen patients with significant electrocardiogram ischemic change were not undertaken with CABG, because coronary artery was not involved by dissection. In these cases, acute aortic valve regurgitation, loss of backward pressure from distal aorta, or valve formation by intimal tear in ascending aorta might decrease diastolic pressure at aortic root and make myocardial ischemia.

Arthroscopic excision of unstable os acromiale associated with impingement syndrome: a case report.

Os acromiale is a rare anatomical variant that is caused by failure of fusion of the acromial apophysis and is usually asymptomatic. We report a case of impingement syndrome of the left shoulder secondary to unstable os acromiale, which was initially overlooked and confirmed only during arthroscopic examination. Arthroscopic excision of the unstable fragment was successful without residual dysfunction of the deltoid muscle.

Heterotopic transplantation of a decellularized and recellularized whole porcine heart.

OBJECTIVES: One of the final treatments for end-stage heart failure is heart transplantation. However, a shortage of donor hearts has created a long waiting list and limited benefits. Our ultimate goal is to create a whole beating heart fabricated on an organ scaffold for human heart transplantation. Here, we successfully performed the first transplantation using a decellularized whole porcine heart with mesenchymal stem cells. METHODS: A porcine heart was harvested following cardiac arrest induced by a high-potassium solution and stored at -80°C for 24 h. The porcine heart was completely decellularized with 1% sodium dodecyl sulphate and 1% Triton X-100 under the control of perfusion pressure (100 mmHg) and maintained at 37°C. A decellularized whole-heart scaffold was sterilized with gamma irradiation. Cultured mesenchymal stem cells were collected and either infused into the ascending aorta or injected directly into the left ventricular wall. Finally, recellularized whole-heart scaffolds were transplanted into pigs under systemic anticoagulation treatment with heparin. Coronary artery angiography of the transplanted heart graft was performed. RESULTS: In our decellularization method, all cellular components were removed, preserving the heart extracellular matrix. Heterotopic transplantations were successfully performed using a decellularized heart and a recellularized heart. The scaffolds were well perfused, without bleeding from the surface or anastomosis site. Coronary angiography revealed a patent coronary artery in both scaffolds. The transplanted decellularized heart was harvested on Day 3. Haematoxylin and eosin staining showed thrombosis in the coronary arteries and migrated inflammatory cells. Haematoxylin and eosin staining of the transplanted recellularized heart showed similar findings, with the exception of injected mesenchymal stem cells. CONCLUSIONS: To the best of our knowledge, this is the first report of heterotopic transplantation of a decellularized whole porcine heart with mesenchymal stem cells. The scaffolds endured surgical procedures. We detected short-term coronary artery perfusion in the transplanted scaffolds by angiography. Future studies should analyse the histological features of transplanted decellularized scaffolds and optimize the system for recellularization to apply this unique technology clinically.