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1.
J Cardiothorac Vasc Anesth ; 36(8 Pt A): 2335-2338, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34756803

RESUMO

OBJECTIVES: This study aimed to investigate whether tracheostomy timing in patients undergoing cardiac surgery had an impact on outcomes. DESIGN: Retrospective, observational study. SETTING: Single-center university hospital. PARTICIPANTS: Patients requiring tracheostomy among a total of 961 patients who underwent cardiovascular surgery via a median sternotomy from January 2014 to March 2021. INTERVENTIONS: Early versus late tracheostomy. MEASUREMENTS AND MAIN RESULTS: During the study period, tracheostomy was performed in 28 patients (2.9%). According to tracheostomy timing, postoperative day seven was chosen as the cutoff to define early (≤seven days) and late (>seven days) tracheostomy. Patients in the early-tracheostomy group had a significantly shorter ventilation time after tracheostomy compared with the late-tracheostomy group (p = 0.039), and early tracheostomy resulted in a reduction in total ventilation time (p = 0.001). The incidence of pressure ulcers was significantly lower in the early-tracheostomy group compared with the late- tracheostomy group. There was a higher tracheal tube removal rate in the early-tracheostomy group compared with the late-tracheostomy group (p = 0.0007). The one-year survival rate in the early- and late-tracheostomy groups was 65% and 31%, respectively. The long-term mortality rate was significantly lower in the early-tracheostomy group compared with the late- tracheostomy group (p = 0.04). CONCLUSIONS: Early tracheostomy (

Assuntos
Cuidados Críticos , Traqueostomia , Cuidados Críticos/métodos , Humanos , Tempo de Internação , Respiração Artificial/métodos , Estudos Retrospectivos , Fatores de Tempo , Traqueostomia/efeitos adversos , Traqueostomia/métodos
3.
Ann Thorac Cardiovasc Surg ; 27(5): 317-321, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34053960

RESUMO

PURPOSE: Unlike loop diuretics, tolvaptan is reported to have a renal protective effect. The purpose of this study was to retrospectively assess the efficacy of tolvaptan administration in chronic kidney disease (CKD) patients following open-heart surgery. METHODS: From February 2017 to August 2020, 75 patients with preoperative CKD stages IIIb-V were enrolled in this study and were divided into two groups: the control group (n = 30) and the tolvaptan group (n = 45). All patients routinely received conventional diuretics starting from postoperative day (POD) 1. Tolvaptan at 7.5-15 mg/day was administered if the patients had persistent fluid retention or poor response to conventional diuretics. RESULTS: Tolvaptan administration was initiated at a mean of POD 2.9 ± 2.2, and the mean dosing period was 4.1 ± 3.0 days. The mean time to return to the preoperative body weight in the control and tolvaptan groups was similar. However, estimated glomerular filtration rate (eGFR) was significantly increased at the time when body weight reached the preoperative level and at discharge in the tolvaptan group than in the control group. CONCLUSION: This study demonstrated the renal protective effect of tolvaptan even in advanced CKD patients after open-heart surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Insuficiência Renal Crônica , Tolvaptan , Humanos , Substâncias Protetoras , Insuficiência Renal Crônica/prevenção & controle , Estudos Retrospectivos , Tolvaptan/uso terapêutico , Resultado do Tratamento
4.
Gen Thorac Cardiovasc Surg ; 69(11): 1467-1475, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33797692

RESUMO

OBJECTIVES: Acute type A aortic dissection complicated with brain ischemia is associated with significantly higher mortality risks. Even if rescued with central aortic repair, some patients develop permanent postoperative neurological deficiency postoperatively. We recently introduced direct common carotid artery perfusion for acute type A aortic dissection involving the common carotid artery. This study introduced this technique to prevent postoperative neurological deficiency by comparing brain protection strategies. METHODS: Among 91 acute type A aortic dissection patients treated at our hospital during August 2015-October 2020, the common carotid artery was involved in 19 (21%), which had > 90% stenosis in either of the carotid arteries on preoperative contrast-enhanced computed tomography. Twelve patients underwent conventional selective cerebral perfusion during August 2015-December 2018 and seven patients underwent direct carotid artery perfusion during January 2019-October 2020. We assessed patient characteristics, surgical courses, clinical outcomes, and neurological outcomes. RESULTS: The mean age was 69 (range 39-84) years; 17 patients were male (89%). Eight patients (42%) had neurological symptoms. Concomitant procedures, postoperative neurological symptoms, and late mortality were significantly associated with conventional selective cerebral perfusion. Five selective cerebral perfusion patients experienced worsened neurological symptoms and two died of broad cerebral ischemia. No direct carotid artery perfusion patient died during hospitalization or experienced worsened neurological outcomes. CONCLUSIONS: Direct carotid artery perfusion may be useful in aortic dissection with brain ischemia because it does not aggravate neurological symptoms and is not associated with intraoperative cerebral infarction. However, it may be ineffective when cerebral infarction has already developed.


Assuntos
Dissecção Aórtica , Artéria Carótida Primitiva , Adulto , Idoso , Idoso de 80 Anos ou mais , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Artérias Carótidas , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Perfusão
5.
J Cardiothorac Surg ; 16(1): 37, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33743755

RESUMO

BACKGROUND: Takayasu arteritis (TA) is a chronic inflammatory disease that induces stenosis, occlusion, or aneurysmal degeneration of the aorta and its major branches. Though rarely reported, proximal aneurysmal lesions from the aortic root to the arch are more common in Asian populations than in Western populations. In the surgical treatment of TA, anastomotic aneurysm can be problematic. Furthermore, atherosclerotic complications should be considered in surgical treatment for elderly TA patients. CASE PRESENTATION: Here, we report a case of brachiocephalic artery (BCA) aneurysm with TA for which surgical treatment was successful. Though it was solely a lesion of the brachiocephalic artery, after considering the patient's clinical background and the features of TA, we chose a partial arch replacement. Further, for avoidance of anastomotic aneurysm, both distal and proximal anastomosis were reinforced with Teflon felt strips. Preoperative computed tomography detected severe atherosclerotic changes in the arch vessels. The patient underwent partial arch replacement using isolated cerebral perfusion (ICP) for brain protection and recovered without any neurological deficits. CONCLUSIONS: In avoidance with anastomotic aneurysm, reinforcement of the anastomosis was introduced. ICP was effective for brain protection in case with severe atherosclerotic changes.


Assuntos
Aneurisma/cirurgia , Tronco Braquiocefálico/cirurgia , Circulação Extracorpórea , Arterite de Takayasu/cirurgia , Idoso , Anastomose Cirúrgica , Aneurisma/complicações , Aorta/cirurgia , Aterosclerose , Circulação Cerebrovascular , Humanos , Inflamação , Masculino , Perfusão , Arterite de Takayasu/complicações , Tomografia Computadorizada por Raios X
6.
Clin Case Rep ; 8(12): 3154-3157, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33363897

RESUMO

Few studies have reported resternotomy after an omental flap procedure. We describe the case of a 78-year-old man who received resternotomy after omental flap procedure for deep sternal wound infection and successfully underwent coronary artery bypass grafting. Although preoperative computed tomography showed funnel chest and limited space between the sternum and omentum, resternotomy was performed safely using circular electric sternum saw under partial cardiopulmonary bypass. Because the omentum functioned as cushioning material between the sternum and mediastinal organs, no injuries of the mediastinal organs occurred. An ultrasonic scalpel effectively dissected between the omentum and mediastinal organs, especially above the ascending aorta. The targeted coronary arteries were easily detected. The patient experienced no major cardiac or infectious events for three months. An ultrasonic scalpel is recommended for dissecting between the omentum and mediastinal organs.

7.
J Card Surg ; 35(11): 3004-3009, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32840908

RESUMO

BACKGROUND AND AIM: Mesenteric malperfusion is a complication with a higher risk of in-hospital mortality because diagnosing mesenteric ischemia before necrotic change is difficult, and when it occurs, the patient's condition has worsened. Although it contradicts the previous consensus on central repair-first strategy, the revascularization-first strategy was found to be significantly associated with lower mortality rates. This study aimed to present our revascularization-first strategy and the postoperative results for acute aortic dissection involving mesenteric malperfusion. METHODS: Among 58 patients with acute type A aortic dissection at our hospital between January 2017 and December 2019, mesenteric malperfusion was noted in six. Four hemodynamically stable patients underwent mesenteric revascularization with endovascular intervention in a hybrid operation room before central repair, and two hemodynamically unstable patients underwent central repair before mesenteric revascularization. RESULTS: No in-hospital mortality was recorded. All four patients with mesenteric revascularization-first strategy recovered with no symptoms related to mesenteric ischemia. Two patients with central repair-first strategy developed paralytic ileus for 1 week; one of them needed exploratory laparotomy, but no patients needed colon resection. CONCLUSION: No in-hospital mortality was recorded. All four patients with mesenteric revascularization-first strategy recovered with no symptoms related to mesenteric ischemia. Two patients with central repair-first strategy developed paralytic ileus for 1 week; one of them needed exploratory laparotomy, but no patients needed colon resection.


Assuntos
Aneurisma Aórtico/complicações , Aneurisma Aórtico/cirurgia , Dissecção Aórtica/complicações , Dissecção Aórtica/cirurgia , Procedimentos Endovasculares/métodos , Isquemia Mesentérica/etiologia , Isquemia Mesentérica/cirurgia , Doença Aguda , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Pseudo-Obstrução Intestinal/cirurgia , Laparotomia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Risco , Resultado do Tratamento
8.
Interact Cardiovasc Thorac Surg ; 30(5): 792-793, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32068841

RESUMO

We report the successful repair in a 29-year-old man who experienced penetration of the ascending aorta and bronchus by a crossbow bolt. Imaging studies revealed the arrow penetrating the sternum, right lung, ascending aorta and right bronchus, with mediastinal emphysema. The top of the arrow (8 mm in diameter) was deeply embedded in the body of the thoracic vertebra. The arrow was successfully removed while maintaining a stable respiratory condition by performing differential lung ventilation. There was no need for cardiopulmonary bypass. To our knowledge, this is the first case of a through-and-through penetrating ascending aorta injury.


Assuntos
Aorta/lesões , Brônquios/lesões , Esterno/lesões , Vértebras Torácicas/lesões , Ferimentos Penetrantes/etiologia , Ferimentos Penetrantes/cirurgia , Adulto , Humanos , Masculino
9.
Gen Thorac Cardiovasc Surg ; 68(5): 499-502, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31595412

RESUMO

OBJECTIVES: Acute pulmonary thromboembolism is a fatal condition with high mortality rate in patients with hemodynamic collapse. Early diagnosis and aggressive treatment after circulatory collapse due to pulmonary thromboembolism are important. Although catheter-directed therapy or surgical thromboembolectomy could be considered, the prognosis of such cases is poor. METHODS: We reviewed nine consecutive patients who underwent surgical intervention for acute pulmonary thromboembolism requiring cardiopulmonary resuscitation from March 2010 to May 2017. The patients' demographics, risk factors, operative and postoperative outcomes were retrospectively analyzed. All nine patients who experienced cardiopulmonary arrest or pulseless electrical activity had received cardiopulmonary resuscitation, including endotracheal intubation with cardiac massage. Computed tomography revealed massive pulmonary thromboembolism. Percutaneous cardiopulmonary support was initiated in six cases. Pulmonary thromboembolectomy was performed on a beating heart without aortic cross-clamping in all patients RESULTS: The mean operation time was 251.9 ± 74.7 min. Among the six patients who received preoperative percutaneous cardiopulmonary support, three were able to wean off cardiopulmonary bypass during the surgery. The other three cases were able to wean off within 3 days postoperatively. The mean postoperative intubation time was 56.3 h. No mortality was observed. All patients were discharged with New York Heart Association functional class I without any neurological complications. No patients developed major and residual thrombi in the pulmonary artery upon postoperative computed tomography. CONCLUSIONS: Pulmonary thromboembolectomy on a beating heart for acute pulmonary thromboembolism may be beneficial for minimizing right ventricular damage and improving clinical outcomes.


Assuntos
Embolia Pulmonar/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Disfunção Ventricular Direita/complicações , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Ponte Cardiopulmonar , Feminino , Humanos , Intubação Intratraqueal , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Período Pós-Operatório , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
10.
J Cardiothorac Surg ; 14(1): 93, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101055

RESUMO

BACKGROUND: Left ventricular (LV) pseudo-false aneurysm is a rare complication secondary to myocardial infarction and is caused by intramyocardial dissecting hematoma due to fragile myocardium. Very occasionally, intramyocardial dissecting hematoma appears as a neocavitation entirely contained within the myocardial wall (so called "pseudo-false LV") and is an unusual form of subacute cardiac rupture. CASE PRESENTATION: A 38-year-old male experienced chest discomfort 3 weeks ago, which improved within few days. However, after that episode, he presented at our hospital with rapidly deteriorating severe breathlessness in a preshock state with acute heart failure. Emergency coronary angiography revealed an occluded left anterior descending artery. An intra-aortic balloon catheter was inserted because of unstable hemodynamics. Enhanced computed tomography revealed extensive aneurysm formation in the LV anterior wall and contrast leakage from the inner cavity to the LV myocardium, with a moderately accumulated pericardial effusion. Emergency surgery revealed a large aneurysmal sac on the anterior wall, slightly attached to the pericardium. A 5-mm, slit-like, oozing-type, rupture site was detected in the LV after dissecting the pericardium. CONCLUSIONS: To our knowledge, this is the first report of a pseudo-false aneurysm on the LV anterior wall. Subacute rupture of pseudo-false LV aneurysm is rare.


Assuntos
Falso Aneurisma/diagnóstico , Aneurisma Roto/diagnóstico , Infarto Miocárdico de Parede Anterior/diagnóstico , Aneurisma Cardíaco/diagnóstico , Ventrículos do Coração , Adulto , Falso Aneurisma/complicações , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/cirurgia , Aneurisma Roto/complicações , Aneurisma Roto/diagnóstico por imagem , Aneurisma Roto/cirurgia , Infarto Miocárdico de Parede Anterior/complicações , Infarto Miocárdico de Parede Anterior/diagnóstico por imagem , Infarto Miocárdico de Parede Anterior/cirurgia , Angiografia Coronária , Diagnóstico Diferencial , Aneurisma Cardíaco/complicações , Aneurisma Cardíaco/diagnóstico por imagem , Aneurisma Cardíaco/cirurgia , Humanos , Masculino
11.
J Cardiothorac Surg ; 13(1): 83, 2018 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-29970121

RESUMO

BACKGROUND: Massive dilatation of the right atrium with tricuspid regurgitation is frequently diagnosed by accidental recognition of an enlarged cardiac silhouette during routine chest radiography. Although some patients are asymptomatic, enlargement of the right atrium can cause secondary tricuspid regurgitation due to dilatation of the tricuspid annulus, associated with arrhythmias and thrombus formation leading to pulmonary embolism, stroke, and, rarely, sudden death due to left ventricular compression. CASE PRESENTATION: A 76-year-old woman was followed up due to atrial fibrillation and tricuspid regurgitation for 8 years. A follow-up echocardiogram showed progressive dilatation of the right atrium. Because of the development of shortness of breath, right atrial plication and tricuspid valve repair were performed. Tricuspid annuloplasty was performed on the beating heart with the use of a 28-mm Carpentier-Edwards Physio tricuspid annuloplasty ring. Plication of the enlarged right atrium was performed at the interatrial septum, the free right atrium wall including the appendage, and the space between the inferior vena cava and the tricuspid ring. Closure of the left atrial appendage was performed from outside to prevent left atrial thrombus formation. Postoperative X-ray and computed tomography showed reduced cardiac silhouette and right atrial volume. The patient was discharged uneventfully and returned for follow-up visits with improved symptoms. CONCLUSIONS: An adult case of massive dilatation of the right atrium of unknown etiology is reported. The patient's symptoms were relieved by our operative procedure.


Assuntos
Átrios do Coração/cirurgia , Anuloplastia da Valva Mitral/métodos , Valva Mitral/cirurgia , Pericárdio/transplante , Retalhos Cirúrgicos , Insuficiência da Valva Tricúspide/cirurgia , Valva Tricúspide/cirurgia , Idoso , Função do Átrio Direito , Procedimentos Cirúrgicos Cardíacos/métodos , Dilatação Patológica/complicações , Dilatação Patológica/diagnóstico , Dilatação Patológica/cirurgia , Progressão da Doença , Ecocardiografia , Feminino , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/fisiopatologia , Humanos , Valva Mitral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/complicações , Insuficiência da Valva Tricúspide/diagnóstico
12.
Interact Cardiovasc Thorac Surg ; 26(3): 512-513, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29087491

RESUMO

Postinfarction ventricular septal defect has been a challenge to cardiac surgeons. Recently, a number of reports have recommended ventricular septal defect closure through the right ventricle. However, when inferior myocardial infarction widely extends to the left ventricle, it is necessary to modify a patch-closure technique due to extensive fragile necrotic myocardium. We describe a simplified surgical technique via a right ventricular incision.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Comunicação Interventricular/cirurgia , Ventrículos do Coração/cirurgia , Infarto do Miocárdio/complicações , Técnicas de Fechamento de Ferimentos , Comunicação Interventricular/etiologia , Humanos
13.
Kyobu Geka ; 66(11): 960-4, 2013 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-24105110

RESUMO

The management of an extended aortic arch aneurysm still remains a clinical challenge. Open surgery can be invasive for the patients with comorbidities. Since thoracic endovascular aneurysm repair (TEVAR) was introduced, hybrid therapy has been applied for the extended arch aneurysm. From 1997 to 2013, 379 patients have undergone aortic arch surgery. Of those, 241 patients of non-dissection aneurysm were studied. Open surgical repair with L-shaped thoracotomy was done in 28 patients, frozen elephant trunk( FET) in 30 patients, long elephant trunk( LET) with 2nd TEVAR in 21 patients, debranched TEVAR in 10 patients and standard arch grafting in 152 patients as a control group. The brain infarction rate was high in debranched TEVAR (40%) and L-shaped group (25%). The paraplegia rate was high in FET group( 23.3%). The respiratory failure rate was high in the L-shaped group and the LET group. In-hospital mortality was 0.0% in the L-shaped group, 6.7% in the FET group, 4.8% in the LET group, 20% in the debranched group and 0.7% in the control group. The debranched TEVAR group is our early experience, and the recent outcomes of this procedure have improved. The management of extended aortic arch aneurysm has changed with hybrid approach combined with TEVAR. Open repair is still the gold standard, but hybrid therapy is used for high-risk patients. Off-pump debranched TEVAR tends to be applied for extended arch aneurysm.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Idoso , Feminino , Humanos , Masculino , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Vasculares/métodos
14.
J Artif Organs ; 16(2): 164-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23334448

RESUMO

Definitive endovascular techniques have been developed for pacemaker lead extraction; however, a few patients require immediate secondary open heart surgery because of incomplete transvenous lead extraction. This study examined the safety, effectiveness, and long-term outcome of the removal of cardiovascular implantable electronic device (CIED) via median sternotomy under cardiopulmonary bypass. The removal of CIED was performed in 6 patients (mean age 57 ± 16 years, 5 males and 1 female), from September 2000 to April 2011. The reasons for removal included eradication of an infection in 5 patients and elimination of pacemaker component allergy in 1. Positive culture results, including methicillin-sensitive Staphylococcus aureus (MSSA, n = 2), methicillin-resistant S. aureus (MRSA, n = 1), coagulase-negative staphylococci (CNS, n = 1), and methicillin-resistant S. epidermidis (MRSE, n = 1) were observed in all 5 infected patients. Mitral annuloplasty (n = 1), mitral valvuloplasty (n = 1), tricuspid annuloplasty (n = 3). Implantation of myocardial pacing leads (n = 5) were performed concomitantly (n = 4), or secondarily (n = 1). All 6 patients were alive in good condition at 72 ± 55 months following CIED removal. New device infection occurred in 1 patient during long-term follow up. Complete surgical removal of pacing systems via median sternotomy with cardiopulmonary bypass is, therefore, considered to be safe and feasible with acceptable long term results.


Assuntos
Ponte Cardiopulmonar , Remoção de Dispositivo , Endocardite Bacteriana/microbiologia , Marca-Passo Artificial , Infecções Relacionadas à Prótese/microbiologia , Adulto , Idoso , Endocardite Bacteriana/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Marca-Passo Artificial/microbiologia , Desenho de Prótese , Infecções Relacionadas à Prótese/terapia , Esternotomia , Resultado do Tratamento
15.
Mol Ther ; 21(3): 662-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23319053

RESUMO

Direct intracardiac cell injection for heart repair is hindered by numerous limitations including: cell death, poor spreading of the injected cells, arrhythmia, needle injury, etc. Tissue-engineered cell sheet implantation has the potential to overcome some of these limitations. We evaluated whether the transplantation of a muscle-derived stem cell (MDSC) sheet could improve the regenerative capacity of MDSCs in a chronic model of myocardial infarction. MDSC sheet-implanted mice displayed a reduction in left ventricle (LV) dilation and sustained LV contraction compared with the other groups. The MDSC sheet formed aligned myotubes and produced a significant increase in capillary density and a reduction of myocardial fibrosis compared with the other groups. Hearts transplanted with the MDSC sheets did not display any significant arrhythmias and the donor MDSC survival rate was higher than the direct myocardial MDSC injection group. MDSC sheet implantation yielded better functional recovery of chronic infarcted myocardium without any significant arrhythmic events compared with direct MDSC injection, suggesting this cell sheet delivery system could significantly improve the myocardial regenerative potential of the MDSCs.


Assuntos
Arritmias Cardíacas/prevenção & controle , Células Musculares/citologia , Infarto do Miocárdio/fisiopatologia , Transplante de Células-Tronco , Células-Tronco/citologia , Engenharia Tecidual , Animais , Arritmias Cardíacas/fisiopatologia , Capilares/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Mioblastos/citologia , Mioblastos/metabolismo , Mioblastos/transplante , Infarto do Miocárdio/terapia , Miocárdio/citologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Função Ventricular Esquerda
16.
Stem Cells ; 31(2): 305-16, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23165704

RESUMO

Human microvascular pericytes (CD146(+)/34(-)/45(-)/56(-)) contain multipotent precursors and repair/regenerate defective tissues, notably skeletal muscle. However, their ability to repair the ischemic heart remains unknown. We investigated the therapeutic potential of human pericytes, purified from skeletal muscle, for treating ischemic heart disease and mediating associated repair mechanisms in mice. Echocardiography revealed that pericyte transplantation attenuated left ventricular dilatation and significantly improved cardiac contractility, superior to CD56+ myogenic progenitor transplantation, in acutely infarcted mouse hearts. Pericyte treatment substantially reduced myocardial fibrosis and significantly diminished infiltration of host inflammatory cells at the infarct site. Hypoxic pericyte-conditioned medium suppressed murine fibroblast proliferation and inhibited macrophage proliferation in vitro. High expression by pericytes of immunoregulatory molecules, including interleukin-6, leukemia inhibitory factor, cyclooxygenase-2, and heme oxygenase-1, was sustained under hypoxia, except for monocyte chemotactic protein-1. Host angiogenesis was significantly increased. Pericytes supported microvascular structures in vivo and formed capillary-like networks with/without endothelial cells in three-dimensional cocultures. Under hypoxia, pericytes dramatically increased expression of vascular endothelial growth factor-A, platelet-derived growth factor-ß, transforming growth factor-ß1 and corresponding receptors while expression of basic fibroblast growth factor, hepatocyte growth factor, epidermal growth factor, and angiopoietin-1 was repressed. The capacity of pericytes to differentiate into and/or fuse with cardiac cells was revealed by green fluorescence protein labeling, although to a minor extent. In conclusion, intramyocardial transplantation of purified human pericytes promotes functional and structural recovery, attributable to multiple mechanisms involving paracrine effects and cellular interactions.


Assuntos
Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Miocárdio/patologia , Pericitos/transplante , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Técnicas de Cultura de Células , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Fibrose/prevenção & controle , Expressão Gênica , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Fator Inibidor de Leucemia/genética , Fator Inibidor de Leucemia/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/genética , Miocárdio/metabolismo , Neovascularização Fisiológica , Pericitos/fisiologia , Proteínas Proto-Oncogênicas c-sis/genética , Proteínas Proto-Oncogênicas c-sis/metabolismo , Regeneração/fisiologia , Transplante Heterólogo , Ultrassonografia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Tissue Eng Part A ; 18(11-12): 1101-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22280442

RESUMO

Stem cell therapy for tissue repair is a rapidly evolving field and the factors that dictate the physiological responsiveness of stem cells remain under intense investigation. In this study we hypothesized that the mechanical loading history of muscle-derived stem cells (MDSCs) would significantly impact MDSC survival, host tissue angiogenesis, and myocardial function after MDSC transplantation into acutely infarcted myocardium. Mice with acute myocardial infarction by permanent left coronary artery ligation were injected with either nonstimulated (NS) or mechanically stimulated (MS) MDSCs. Mechanical stimulation consisted of stretching the cells with equibiaxial stretch with a magnitude of 10% and frequency of 0.5 Hz. MS cell-transplanted hearts showed improved cardiac contractility, increased numbers of host CD31+ cells, and decreased fibrosis, in the peri-infarct region, compared to the hearts treated with NS MDSCs. MS MDSCs displayed higher vascular endothelial growth factor expression than NS cells in vitro. These findings highlight an important role for cyclic mechanical loading preconditioning of donor MDSCs in optimizing MDSC transplantation for myocardial repair.


Assuntos
Infarto do Miocárdio/terapia , Transplante de Células-Tronco , Células-Tronco/citologia , Estresse Mecânico , Animais , Fenômenos Biomecânicos , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular , Cicatriz/patologia , Cicatriz/fisiopatologia , Modelos Animais de Doenças , Testes de Função Cardíaca , Precondicionamento Isquêmico Miocárdico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Neovascularização Fisiológica , Estresse Oxidativo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
Mol Ther ; 20(1): 138-45, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22068427

RESUMO

Identification of cells that are endowed with maximum potency could be critical for the clinical success of cell-based therapies. We investigated whether cells with an enhanced efficacy for cardiac cell therapy could be enriched from adult human skeletal muscle on the basis of their adhesion properties to tissue culture flasks following tissue dissociation. Cells that adhered slowly displayed greater myogenic purity and more readily differentiated into myotubes in vitro than rapidly adhering cells (RACs). The slowly adhering cell (SAC) population also survived better than the RAC population in kinetic in vitro assays that simulate conditions of oxidative and inflammatory stress. When evaluated for the treatment of a myocardial infarction (MI), intramyocardial injection of the SACs more effectively improved echocardiographic indexes of left ventricular (LV) remodeling and contractility than the transplantation of the RACs. Immunohistological analysis revealed that hearts injected with SACs displayed a reduction in myocardial fibrosis and an increase in infarct vascularization, donor cell proliferation, and endogenous cardiomyocyte survival and proliferation in comparison with the RAC-treated hearts. In conclusion, these results suggest that adult human skeletal muscle-derived cells are inherently heterogeneous with regard to their efficacy for enhancing cardiac function after cardiac implantation, with SACs outperforming RACs.


Assuntos
Fibras Musculares Esqueléticas/transplante , Isquemia Miocárdica/terapia , Estresse Fisiológico , Adolescente , Idoso , Animais , Apoptose/genética , Adesão Celular , Diferenciação Celular , Proliferação de Células , Sobrevivência Celular/genética , Cicatriz/patologia , Perfilação da Expressão Gênica , Humanos , Imunofenotipagem , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/metabolismo , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Neovascularização Fisiológica , Estresse Oxidativo
19.
Mol Ther ; 19(4): 790-6, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21304494

RESUMO

Wnt signaling plays a crucial role in regulating cell proliferation, differentiation and inducing cardiomyogenesis. Skeletal muscle-derived stem cells (MDSCs) have been shown to be multipotent; however, their potential to aid in the healing of the heart after myocardial infarction appears to be due to the paracrine effects they impart on the host environment. The goal of this study was to investigate whether Wnt11 could promote the differentiation of MDSCs into cardiomyocytes and enhance the repair of infarcted myocardium. MDSCs transduced with a lentivirus encoding for Wnt11 increased mRNA and protein expression of the early cardiac markers NK2 transcription factor related 5 (NKx2.5) and Connexin43 (Cx43) and also led to an increased expression of late-stage cardiac markers including: α, ß-myosin heavy chain (MHC) and brain natriuretic protein (BNP) at the mRNA level, and MHC and Troponin I (TnI) at the protein level. We also observed that Wnt11 expression significantly enhanced c-jun N-terminal kinase activity in transduced MDSCs, and that some of the cells beat spontaneously but are not fully differentiated cardiomyocytes. Finally, lentivirus-Wnt11-transduced MDSCs showed greater survival and cardiac differentiation after being transplanted into acutely infarct-injured myocardium. These findings could one day lead to strategies that could be utilized in cardiomyoplasty treatments of myocardial infarction.


Assuntos
Diferenciação Celular/fisiologia , Vetores Genéticos/genética , Lentivirus/genética , Fibras Musculares Esqueléticas/citologia , Células-Tronco/citologia , Células-Tronco/metabolismo , Proteínas Wnt/metabolismo , Animais , Western Blotting , Diferenciação Celular/genética , Imuno-Histoquímica , Masculino , Camundongos , Camundongos SCID , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas Wnt/genética
20.
Biomaterials ; 31(30): 7678-83, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20674011

RESUMO

Injectable biomaterials have been recently investigated as a therapeutic approach for cardiac repair. Porcine-derived small intestinal submucosa (SIS) material is currently used in the clinic to promote accelerated wound healing for a variety of disorders. In this study, we hypothesized that gels derived from SIS extracellular matrix would be advantageous as an injectable material for cardiac repair. We evaluated 2 forms of SIS gel, types B (SIS-B) and C (SIS-C), for their ability to provide a therapeutic effect when injected directly into ischemic myocardium using a murine model of an acute myocardial infarction. Echocardiography analysis at both 2 and 6 weeks after infarction demonstrated preservation of end-systolic left ventricular geometry and improvement of cardiac contractility in the hearts injected with SIS-B when compared with control hearts injected with saline. However, the SIS-C gel provided no functional efficacy in comparison with control. Histological analysis revealed that SIS-B reduced infarct size and induced angiogenesis relative to control, whereas injection of SIS-C had minimal effect on these histological parameters. Characterization of both gels revealed differential growth factor content with SIS-B exhibiting higher levels of basic fibroblast growth factor than SIS-C, which may explain, at least in part, the differential histological and functional results. This study suggests that SIS gel offers therapeutic potential as an injectable material for the repair of ischemic myocardium. Further understanding of SIS gel characteristics, such as biological and physical properties, that are critical determinants of efficacy would be important for optimization of this biomaterial for cardiac repair.


Assuntos
Materiais Biocompatíveis , Géis , Mucosa Intestinal/química , Intestino Delgado/anatomia & histologia , Infarto do Miocárdio/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Ecocardiografia , Géis/química , Géis/farmacologia , Géis/uso terapêutico , Coração/efeitos dos fármacos , Injeções , Masculino , Teste de Materiais , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Infarto do Miocárdio/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Suínos , Resultado do Tratamento
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