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1.
J Tissue Viability ; 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38825443

RESUMEN

BACKGROUND: The development of models using deep learning (DL) to assess pressure injuries from wound images has recently gained attention. Creating enough supervised data is important for improving performance but is time-consuming. Therefore, the development of models that can achieve high performance with limited supervised data is desirable. MATERIALS AND METHODS: This retrospective observational study utilized DL and included patients who received medical examinations for sacral pressure injuries between February 2017 and December 2021. Images were labeled according to the DESIGN-R® classification. Three artificial intelligence (AI) models for assessing pressure injury depth were created with a convolutional neural network (Categorical, Binary, and Combined classification models) and performance was compared among the models. RESULTS: A set of 414 pressure injury images in five depth stages (d0 to D4) were analyzed. The Combined classification model showed superior performance (F1-score, 0.868). The Categorical classification model frequently misclassified d1 and d2 as d0 (d0 Precision, 0.503), but showed high performance for D3 and D4 (F1-score, 0.986 and 0.966, respectively). The Binary classification model showed high performance in differentiating between d0 and d1-D4 (F1-score, 0.895); however, performance decreased with increasing number of evaluation steps. CONCLUSION: The Combined classification model displayed superior performance without increasing the supervised data, which can be attributed to use of the high-performance Binary classification model for initial d0 evaluation and subsequent use of the Categorical classification model with fewer evaluation steps. Understanding the unique characteristics of classification methods and deploying them appropriately can enhance AI model performance.

2.
J Craniofac Surg ; 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37830806

RESUMEN

The keystone flap has become an established option that has been utilized recently to close significant myelomeningocele defects. Although the keystone flaps can be adapted to repair myelomeningocele defects of different sizes, the shape of the defect is also an essential factor to consider. In this study, the authors proposed an algorithmic approach for reconstructing significant meningomyelocele defects utilizing different types of keystone flaps based on the shape of the resulting defect. From September 2016 to March 2022, the authors retrospectively reviewed the medical records of 28 patients with meningomyelocele who underwent repair with the keystone flaps. The mean age was 28 days (3 days to 4.5 months). Twenty-one meningomyelocele defects were in the lumbosacral (75%) and 7 in the thoracolumbar regions (25%). The defect sizes ranged from 3.5×5 cm (area, 13.4 cm2) to 9×7 cm (area, 49.5 cm2), with an average of 26.2 cm2. Ten meningomyelocele defects were a vertically oriented oval shape, 16 defects were a transversely oriented oval shape, and 2 defects were circular. In addition, unilateral keystone flap was used in 7.1% of the patients (2 patients), bilateral keystone flap in 28.6% (8 patients), and rotation advancement keystone flaps in 64.3% (18 patients). According to these findings, an algorithm was created based on the defect shape. This algorithmic approach is used as a decision-making guide to select the correct type of keystone flaps to repair myelomeningocele according to the defect shape.

3.
Nagoya J Med Sci ; 85(2): 255-264, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37346845

RESUMEN

In lateral skull base reconstruction, it is necessary to seal the defect in the lateral skull base, fill the dead space, and, sometimes, reconstruct the facial nerve. However, this procedure is difficult to perform with a standard musculocutaneous flap. Therefore, for such cases, an omental flap is used in our hospital because of its flexibility. In this study, we report our experience with the procedure (lateral skull base reconstruction with a free omental flap) and its long-term outcome and facial nerve reconstruction, with special focus on facial nerve recovery. This study is a technical note and a retrospective review. It was conducted in Nagoya University Hospital. Overall, 16 patients (12 women and 4 men; mean age: 55.1 years) underwent lateral skull base reconstruction with a free omental flap after subtotal temporal bone resection or lateral temporal bone resection during 2005-2017. The main outcome measures were postoperative complications and facial nerve recovery: Yanagihara score and House-Brackmann grading system. Complications included partial necrosis and minor cerebrospinal fluid leakage in 2 patients. Facial nerve recovery could be observed more than 12 months after surgery, with a mean Yanagihara score of 19.6 and House-Brackmann grade of 3.60. The free omental flap is a reliable method for lateral skull base reconstruction, especially in cases where facial nerve reconstruction is needed. To the best of our knowledge, this is the first report on facial nerve recovery after lateral skull base reconstruction.

4.
ORL J Otorhinolaryngol Relat Spec ; 85(5): 275-283, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37285823

RESUMEN

INTRODUCTION: Free jejunal flap (FJF) reconstruction is a standard procedure for pharyngeal and cervical esophageal defects resulting from head and neck cancer resection. However, improvements in patients' quality of life after surgery require a further statistical approach. METHODS: An observational, retrospective, multivariate analysis was designed to report the incidence of postoperative complications and their association with clinical factors in 101 patients who underwent total pharyngo-laryngo-esophagectomy and FJF reconstruction for head and neck cancer at a university hospital between January 2007 and December 2020. RESULTS: Postoperative complications were observed in 69% of patients. In the reconstructive site, anastomotic leak, observed in 8% of patients was associated with vascular anastomosis in the external jugular vein system (age-adjusted odds ratio [OR]: 9.05, p = 0.044) and anastomotic stricture, observed in 11% of patients was associated with postoperative radiotherapy (age-adjusted OR: 12.60, p = 0.02). Cervical skin flap necrosis was the most common complication (34%) and was associated with vascular anastomosis on the right cervical side (age- and sex-adjusted OR: 4.00, p = 0.005). CONCLUSION: Although FJF reconstruction is a useful procedure, 69% of patients suffer a postoperative complication. We suppose that anastomotic leak is related to the low blood flow resistance of the FJF and inadequate drainage of the external jugular venous system, and anastomotic stricture is related to the vulnerability of the intestinal tissue to radiation. Furthermore, we hypothesized that the location of the vascular anastomosis may affect the mesenteric location of the FJF and the dead space in the neck, leading to the development of cervical skin flap necrosis. These data contribute to increasing our knowledge about postoperative complications related to FJF reconstruction.


Asunto(s)
Neoplasias Esofágicas , Neoplasias de Cabeza y Cuello , Humanos , Esofagectomía/efectos adversos , Fuga Anastomótica/epidemiología , Fuga Anastomótica/etiología , Fuga Anastomótica/cirugía , Estudios Retrospectivos , Constricción Patológica/complicaciones , Constricción Patológica/cirugía , Calidad de Vida , Neoplasias de Cabeza y Cuello/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Necrosis/complicaciones , Necrosis/cirugía , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/complicaciones
5.
Yonago Acta Med ; 66(2): 317-321, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37234222

RESUMEN

When resecting the internal jugular veins bilaterally in surgery for head and neck cancer, it is necessary to perform neck dissection in two stages or to reconstruct the internal jugular veins in one stage. Reconstruction of the internal jugular vein using grafting or direct anastomosis to the external jugular vein have both been reported. We report the case of a 53-year-old man with accidental injury to the left internal jugular vein after resection of the right internal jugular vein for supraglottic cancer. The left internal jugular vein was damaged near the inflow of the subclavian vein, making vein grafting difficult. Therefore, internal jugular venous return was reestablished by end-to-side anastomosis of the left internal jugular vein to the left external jugular vein system. In this surgical procedure, by incising the internal jugular vein obliquely, it was not necessary to match the calibers of the internal jugular vein and the external jugular vein system, and a smooth hemodynamic body was reconstructed. In addition, we were able to reconstruct the internal jugular vein while preserving blood flow in the external jugular vein system. End-to-side anastomosis of the internal jugular vein to the external jugular system is an option for internal jugular vein reconstruction.

7.
Yonago Acta Med ; 66(1): 146-152, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36820288

RESUMEN

Background: There is a need for quick skin blood flow tests that can be performed in the wound healing field. Antera 3D® is a compact scanner using multispectral imaging. It can perform quick assessment of skin conditions. The purpose of the present study was to investigate the ability of the Antera 3D® to assess skin blood flow in comparison with transcutaneous partial pressure of oxygen (TcPO2) measurements. Methods: This study was conducted on 13 patients with a history of lower extremity ulcers. Measurements of hemoglobin average level (hereafter, Hb score) measured by Antera 3D® and TcPO2 measured by a transcutaneous blood gas monitor were obtained at the same sites on the dorsal foot and lower leg. Differences in Hb score and TcPO2 were analyzed by t-test for each measurement site and for the presence of peripheral arterial disease (PAD). The correlation between TcPO2 and Hb score was analyzed by Pearson's correlation coefficient. Results: Twenty-four limbs were tested. Hb score was higher (P < 0.001) and TcPO2 was lower (P = 0.056) in the dorsal foot compared to the lower leg. In the dorsal foot, Hb score was higher (P = 0.023) and TcPO2 was lower (P = 0.046) in patients with PAD compared to those without PAD. A significant negative correlation (r = -0.68; 95% confidence interval -0.85 to -0.38, P < 0.001) between TcPO2 and Hb score was observed in the dorsal foot. Conclusion: The negative correlation between TcPO2 and Hb score may reflect compensatory peripheral vasodilation due to occlusion or stenosis of central arteries. This study showed that Hb score measured by Antera 3D® may be related to skin blood flow.

8.
Ann Plast Surg ; 90(2): 171-179, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36688861

RESUMEN

ABSTRACT: Platelet-rich plasma (PRP) and adipose-derived stem cells (ADSCs) are known to secrete angiogenic factors that contribute to the treatment of intractable ulcers. The combination of PRP and ADSCs may enhance their angiogenic effects. However, it remains unclear whether treatment of ADSCs with PRP influences angiogenesis. We studied whether the conditioned medium from PRP-treated ADSCs under hypoxic conditions exerts angiogenic effects. Although PRP stimulated the proliferation of ADSCs obtained from rats, it decreased the mRNA levels of vascular endothelial growth factor, hepatocyte growth factor, and TGF-ß1, but not of basic fibroblast growth factor, under hypoxia. The conditioned medium of PRP-treated ADSCs inhibited endothelial nitric oxide synthase phosphorylation, decreased NO production, and suppressed tube formation in human umbilical vein endothelial cells. Transplantation of ADSCs alone increased both blood flow and capillary density of the ischemic limb; however, its combination with PRP did not further improve blood flow or capillary density. This suggests that both conditioned medium of ADSCs treated with PRP and combination of PRP with ADSCs transplantation may attenuate the phosphorylation of endothelial nitric oxide synthase and angiogenesis.


Asunto(s)
Plasma Rico en Plaquetas , Factor A de Crecimiento Endotelial Vascular , Humanos , Ratas , Animales , Medios de Cultivo Condicionados/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Óxido Nítrico Sintasa de Tipo III , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Neovascularización Fisiológica , Células Madre/metabolismo , Plasma Rico en Plaquetas/metabolismo , Tejido Adiposo/metabolismo , Células Cultivadas
9.
Yonago Acta Med ; 65(4): 296-302, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36474904

RESUMEN

Background: In free flap transfer, size discrepancy between the vascular pedicle and recipient vessel can create a problem for microsurgeons and sometimes induces postoperative thrombus formation. When there is a major difference between the diameters of the vascular pedicle and the recipient vessel, the larger vessel is often tapered to perform the anastomosis properly. However, the decision on the tapering angle used depends mostly on the operator's experience. In this study, computational fluid dynamics (CFD) was used to investigate the optimum tapering angle. Methods: Using ANSYS ICEM 16.0 (ANSYS Japan, Tokyo, Japan), simulated vessels of diameters 1.5 mm and 3.0 mm were designed and then used to produce four anastomosis models with the 3.0-mm vessel tapered at angles of 15º, 30º, 60º, and 90º (no tapering). Venous perfusion with a mean value of 13.0 mL/min was simulated, and this was passed through the four anastomosis models in both the forward direction (F), from the smaller to the larger vessel, and the retrograde direction (R), from the larger to the smaller vessel. The velocity, wall shear stress (WSS), and oscillatory shear index (OSI) were measured in these eight patterns and then analyzed using OpenFOAM version 5. Results: The decrease in velocity was limiting. The WSS was greater in the R direction than the F direction at every tapering angle. The OSI also tended to be almost the same in the F direction, and lower at smaller tapering angles in the R direction. And, it was greater in the F direction than in the R direction at every tapering angle. The OSI values for 15º and 30º were almost identical in the R direction. Conclusion: The risk of thrombus formation is thought to be lower when tapering is used for anastomosis if the direction of flow is from the larger to the smaller vessel, rather than vice versa. These results also suggest that the optimum tapering angle is approximately 30º in both directions.

10.
Yonago Acta Med ; 65(3): 215-225, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36061574

RESUMEN

Background: Although head and neck reconstruction using free flaps has become a common procedure, flap complications remain a concern. This study aimed to analyze the risk factors of free flap complications and to identify the causes of these complications. Methods: We studied 97 patients with head and neck cancer with intraoral defects who underwent reconstruction using free flaps at Tottori University Hospital between 2011 and 2020. We used a retrospective cohort study design to investigate whether flap complications, including flap necrosis (total and partial) and flap dehiscence, were related to various factors, including the underlying disease condition, treatment status, and surgical factors. Results: Of the 97 patients analyzed, total flap necrosis was observed in one patient (1.0%). The incidence rate of flap complications, including flap necrosis and flap dehiscence, was 29.9%. When the time taken to perform one vascular anastomosis, including preparation of the recipient vessel and flap vessel, exceeded 30 min, the incidence rates of flap necrosis (total and partial) (odds ratio, 8.30; 95% confidence interval, 1.91-36.00; P = 0.005) and flap dehiscence (odds ratio, 3.46; 95% confidence interval, 1.05-11.36; P = 0.041) increased significantly. Conclusion: The time taken to perform one vessel anastomosis was the factor that contributed the most to the incidence of flap complications. Reconstructive surgeons should reduce the incidence of flap complications by keeping the known risk factors of the surgery in mind and by aiming to complete a vascular anastomosis time, including the time taken for the preparation of vessels, of ≤ 30 min per vessel during surgery.

11.
Ann Plast Surg ; 89(1): 77-81, 2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35502970

RESUMEN

INTRODUCTION: Myelomeningocele is the most common form of neural tube anomalies. Early reliable skin coverage should be achieved to reduce central nervous system infections. The keystone flaps are gaining popularity for myelomeningocele defect reconstruction. However, the use of a traditional keystone flap is limited in very wide or transversely oriented myleomeningocele defects with inadequate lateral tissue laxity. In this study, we present our successful experience using modified rotation advancement keystone flaps for closure of the transversely oriented myelomeningocele defects. PATIENTS AND METHODS: Between April 2019 and April 2020, the modified rotation advancement keystone flap was used for reconstruction of transversely oriented myelomeningocele defect in 7 patients (5 males and 2 females) with average age of 14 days. The localization of the lesions was lumbosacral in 5 patients and thoracolumbar in 2 patient. The average myelomeningocele defect width was 6.4 cm, whereas the average defect length was 5.7 cm. The following information was evaluated: the flap dimensions, operative time, and postoperative complications. RESULTS: All patients had uneventful operations, except for 1 case of superficial epidermolysis over flap tip, which settled with conservative wound management. Immediate venous congestion was detected in 2 patients that completely resolved. Otherwise, all wounds healed without any evidence of complications. The mean follow-up was 4 months. CONCLUSIONS: Although the conventional keystone flap seems to have geometric constraints to close a transversally oriented myelomeningocele defect, the modified rotation advancement keystone flap serves as a superior alternative and effective option for closure transversally oriented defect.


Asunto(s)
Meningomielocele , Procedimientos de Cirugía Plástica , Adolescente , Femenino , Humanos , Masculino , Meningomielocele/cirugía , Tempo Operativo , Procedimientos de Cirugía Plástica/métodos , Colgajos Quirúrgicos/cirugía , Resultado del Tratamiento
12.
J Tissue Viability ; 31(3): 552-556, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35504795

RESUMEN

OBJECTIVE: Pressure injuries in people with spinal cord injury or dysfunction (SCI/D) are known to have a high recurrence rate. As a countermeasure, we perform surgery after adjusting the wheelchair and cushion with the intervention of a seating expert. The effectiveness of seating interventions in postsurgical recurrence prevention was examined. MATERIALS AND METHODS: In this retrospective analysis, the participants were 19 patients with SCI/D who underwent pressure injury surgical treatment in the gluteal region from 2005 to 2018. The patients with conventional rehabilitation were assigned to Group 1 (n = 8), and those with seating intervention by experts in addition to conventional rehabilitation were assigned to Group 2 (n = 11). The main outcome measure was the presence or absence of recurrence 3 years after the surgery. The recurrence rate was compared between the two groups. RESULTS: The recurrence rates were 18% with seating intervention and 75% without; there was a significant difference (p = 0.025). The recurrence odds ratio was 13.5. CONCLUSION: This study suggests that presurgical seating evaluation and assessment by experts, postsurgical rehabilitation based on presurgical evaluation and assessment, and routine follow-up and seating adjustment according to changes are efficacious for preventing postsurgical pressure injury recurrence in patients with SCI/D.


Asunto(s)
Lesiones por Aplastamiento , Úlcera por Presión , Traumatismos de la Médula Espinal , Silla de Ruedas , Humanos , Oportunidad Relativa , Estudios Retrospectivos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/cirugía , Silla de Ruedas/efectos adversos
14.
Yonago Acta Med ; 64(1): 107-112, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33642909

RESUMEN

BACKGROUND: Subcutaneous injection of tumescent solution, which contains local anesthetic, adrenaline, and saline, before split-thickness skin graft harvesting, shows a significant hemostatic effect. This method can reduce the initial bleeding from the donor site. The aim of this study is to assess the benefits of controlling the bleeding from donor sites by tumescent injection. A randomized, controlled trial was performed to compare the wound healing of split-thickness skin graft donor sites treated with or without tumescent injection. METHODS: This randomized, controlled trial examined donor site healing days as the main measure of outcome. postoperative pain, donor site ulceration, and scar quality were evaluated as secondary outcome measures. Patients planned for split-thickness skin graft harvest were randomly assigned to receive either pre-harvest subcutaneous injection of local anesthetic, adrenaline, and saline solution (tumescent solution) (Group 1) or post-harvest application of adrenaline solution-soaked gauze to the skin graft donor sites (Group 2). Donor sites were treated with calcium alginate dressings after graft harvesting. On the 10th postoperative day, the dressings were removed and donor site healing were measured. Follow-up evaluation of scar quality was performed 6 months after surgery. Postoperative pain was evaluated on the 1st day after operating. RESULTS: Forty-five patients (26 males; average age 61.8 years) completed the late follow-up evaluation (6 months postoperatively), with 26 patients in group 1 and 19 in group 2. There were no significant differences between the two groups in any of the outcome measures. CONCLUSION: Tumescent technique provides sufficient hemostasis in split skin graft donor sites, especially the initial bleeding just after graft harvesting, without any negative effects. Larger series should be studied to evaluate the effect in donor site wound healing.

15.
Yonago Acta Med ; 63(4): 308-312, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33253341

RESUMEN

BACKGROUND: Technical issues in free flap transfer, such as the selection of recipient vessels and the positioning and method of anastomosis of the vascular pedicle, have been the subject of vigorous debate. Recent developments in computational fluid dynamics (CFD) have enabled the analysis of blood flow within microvessels. In this study, CFD was used to analyze hemodynamics in a microanastomosis. METHODS: In the fluid calculation process, the fluid domain modelizes microvessels with anastomosis. The inlet flow conditions were measured as venous waveform, and the fluid is simulated as blood. Streamlines (SL), wall shear stress (WSS), and oscillatory shear index (OSI) at the anastomosis were visualized and analyzed for observing effects from the flow field. RESULTS: Some flow disruption was evident as the SL passed over the sutures. The maximum recorded WSS was 13.37 Pa where the peak of a suture was exposed in the lumen. The local maximum value of the OSI was 0.182, recorded at the base of the anastomosis on the outflow side. CONCLUSION: In the ideal anastomosis, the SL is disrupted as little as possible by the sutures. The WSS indicated that thrombus formation is unlikely to occur at suture peaks, but more likely to occur at the base of sutures, where the OSI is high. Tight suture knots are important in microanastomosis.

16.
Yonago Acta Med ; 63(2): 127-131, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32494219

RESUMEN

Reconstruction of bone and soft-tissue defects in the forearm is a surgery that often proves unsuccessful. Free fibular osteocutaneous flaps are a useful material for reconstruction that enable simultaneous reconstruction of bone, skin, and soft tissues. However, in free fibular osteocutaneous flaps, the fibula, skin, and vascular pedicle are tightly bound together by the posterior intermuscular septum and the perforators that pass through the septum, giving the disadvantage of a low degree of freedom when setting these structures in place. We take into account the 3-dimensional structure of the free skin flap when selecting which lower leg to use as the donor. We report here the case of a 61-year-old man with defects in the radius, skin, and soft tissues after resection of spindle cell carcinoma of the right forearm, which was reconstructed using a free fibular osteocutaneous flap harvested from the left lower leg. Two years postoperatively, recovery has been uneventful with no complications. Donor-side selection of free fibular osteocutaneous flap is an important factor for safely completing composite radius reconstruction.

17.
Biochem Biophys Rep ; 18: 100645, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31193220

RESUMEN

In the present study, we have established a novel transgenic mouse and transgenic rats with dual reporters of EGFP and ELuc. In these transgenic (Tg) rodents, both GFP fluorescent and luciferase luminescent signals were ubiquitously detected in the heart, liver, kidney and testis, while only the GFP signal was detected in the brain. This expression system is based on a P2A linked EGFP/ELuc protein allowing both signals to be generated simultaneously. Microscopy experiments, FCM, and luciferase assays showed strong expression in freshly isolated ADSCs from Tg rodents upon transplantation of Tg rat-derived ADSCs into wild-type-mice. The ELuc transgene signal was observed and traced in vivo, and EGFP positive cells could be recovered from ELuc positive tissues in engraftment sites of wild-type mice for multiple analysis. These dual reporter Tg rodents are a useful reconstituted model system of regenerative medicine and are a valuable tool to study stem cells.

18.
JPRAS Open ; 19: 121-124, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32158865

RESUMEN

OBJECTIVES: Liposuction is now applied to harvest autologous adipose-derived regenerative cells in the regenerative medicine. Although liposuction is highly safe for females who generally have larger fat deposits, liposuction has some potential risks for donor-site complications in the case of aged male patients. The purpose of our study was to review the complications of liposuction of the aged male patients who have undergone cell therapy for stress urinary incontinence. METHODS: Sixteen male patients (mean age, 74 years old) with persistent stress urinary incontinence were included in this study. Approximately 250 mL of adipose tissue was harvested using a syringe attached to the cannula. Postoperative complications were recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. RESULTS: Average liposuction time was 57.4 min. No major complications were observed. However, there were some minor complications: bruising, numbness, contour irregularities, firmness, and scarring. These complications were CTCAE Grade 1 in all cases. The complications, except for the scarring, became unnoticeable within 6 months in all cases. CONCLUSION: Liposuction takes time and has some minor donor-site complications for stem cell therapy in aged male stress urinary incontinence patients.

19.
Regen Ther ; 9: 79-88, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30525078

RESUMEN

INTRODUCTION: Cell sheets using myoblasts have been developed for the treatment of heart failure after myocardial infarction (MI) bridging to heart transplantation. Stem cells are supposed to be better than myoblasts as a source of cells, since they possess a potential to proliferate and differentiate into cardiomyocytes, and also have capacity to secrete angiogenic factors. Adipose-derived stem cells (ASCs) obtained from fat tissues are expected to be a new cell source for ASC sheet therapies. Administration of angiotensin II receptor blockers (ARBs) is a standard therapy for heart failure after MI. However, it is not known whether ARBs affect the cell sheet therapy. This study aimed to examine ameliorating effects of ASC sheets on heart failure and remodeling after MI, and how pretreatment with ARBs prior to the creation of MI and ASC sheet transplantation modifies the effects of ASC sheets. METHODS: ASCs were isolated from fat tissues of wild-type rats, and ASC sheets were engineered on temperature-responsive dishes. In in vitro studies using cultured cells, mRNA levels of vascular endothelial growth factor (VEGF) in ASCs were determined by RT-PCR in the presence of angiotensin II and/or an ARB, irbesartan, under normoxia and hypoxia; mRNA and protein levels of angiotensin II receptor type 1a (AT1aR), type 1b (AT1bR) and type 2 (AT2R) were also determined by RT-PCR and western blotting. In in vivo studies using a rat MI model, effects of transplanted ASC sheets and/or irbesartan on cardiac functions and remodeling after MI were evaluated by echocardiography, histological analysis and molecular biological techniques. RESULTS: In the in vitro studies, ASCs expressed higher levels of VEGF mRNA under hypoxia. They also expressed mRNA and protein of AT1aR but not AT1bR or AT2R. Under normoxia, angiotensin II increased the level of VEGF mRNA in ASCs, which was abolished by irbesartan. Under hypoxia, irbesartan reduced the level of VEGF mRNA in ASCs regardless of whether angiotensin II was present or not. In the in vivo studies, ASC sheets improved cardiac functions after MI, leading to decreased interstitial fibrosis and increased capillary density in border zones. These effects of ASC sheets were abolished by oral administration of irbesartan before MI and their transplantation. CONCLUSIONS: ASC sheets ameliorated cardiac dysfunctions and remodeling after MI via increasing VEGF expression, which was abolished by pretreatment with irbesartan before the creation of MI and transplantation.

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