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1.
Artigo em Inglês | MEDLINE | ID: mdl-38588576

RESUMO

OBJECTIVES: Risk factors for late-term aortic dilation after acute type A aortic dissection repair have not been well examined. The goal of this study was to determine the relationship between the abdominal aortic true lumen location and thoraco-abdominal aortic dilation after surgical repair for acute type A aortic dissection. METHODS: Patients who were preoperatively diagnosed with acute type A aortic dissection between April 2014 and July 2022 were included in this study. We evaluated the renal artery-level dissected aortic morphology and classified the study population into 2 groups: the ventral (those with the true lumen located on the ventral side) and the dorsal (other patients not assigned to the ventral group) groups, based on the location of the true lumen. Aortic dilation was defined as thoraco-abdominal aortic expansion ≥5 mm on 1-year postoperative computed tomography images. RESULTS: We examined 49 surgical patients who were assigned to the ventral (n = 22) and dorsal (n = 27) groups. The number of patients with ≥5 mm thoraco-abdominal aortic dilation after the operation was significantly higher in the ventral group than in the dorsal group (90.9% vs 51.9%, P = 0.009). The multivariable logistic regression analysis showed that the ventral type was an independent prognostic factor for thoraco-abdominal aortic dilation after the operation (odds ratio, 6.01; 95% confidence interval, 1.56-23.77; P = 0.009). CONCLUSIONS: The location of the true lumen of the abdominal aorta in acute type A aortic dissection may be a prognostic factor for thoraco-abdominal aortic dilation after surgical repair.

2.
J Card Surg ; 37(12): 5487-5489, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36168823

RESUMO

BACKGROUND: Reintervention for residual dissection after repaired type A aortic dissection remains challenging. When a frozen elephant trunk (FET) is used, the incidence of distal stent graft-induced new entry (d-SINE) is reportedly high in chronic dissection. AIMS: We report a case of successful redo arch repair using fenestrated and covered FET techniques for chronic residual aortic dissection. METHODS: After the arch was transected proximal to the left subclavian artery (LSCA), and a modified FET prosthesis, in which the distal edge of the FET was covered, was deployed. A fenestration was created in the FET on the LSCA aspect. RESULTS: The postoperative course was uneventful. DISCUSSION: The distal edge of the FET was covered to prevent d-SINE. Creation of a fenestration on the FET eliminates the need to reconstruct the LSCA. CONCLUSION: The fenestrated FET technique simplifies redo arch repair and the covered FET technique can potentially prevent d-SINE.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Humanos , Prótese Vascular , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/métodos , Stents , Resultado do Tratamento , Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Estudos Retrospectivos
3.
J Card Surg ; 37(10): 3101-3109, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35788988

RESUMO

BACKGROUND: We investigated the effects of frozen elephant trunk (FET) implantation on clinical outcomes in patients with acute type A aortic dissection (ATAAD) extending into the renal artery (RA). METHODS: Between May 2016 and April 2021, 136 patients underwent surgery for ATAAD at our hospital. Patients who died within 7 days postoperatively and those without preoperative contrast-enhanced computed tomography (CT) data were excluded from the study. The remaining 125 patients were included in this study. A preoperative CT-documented RA abnormality was found in 53 patients. Clinical outcomes, including renal dysfunction and CT findings, were compared between 29 patients with and 24 patients without the FET prosthesis. RESULTS: Among the 53 patients with RA abnormalities, origin of the RA from the false lumen was the most common type of abnormality. The percentage of men and rate of arch repair were higher, and the operation, cardiopulmonary bypass, and lower body hypothermic circulatory arrest times were longer in the FET than in the non-FET group. Early mortality rates were similar between groups. The incidence of postoperative acute kidney injury (AKI) was lower in the FET group (35% vs. 67%, p = 0.028). Multivariable analysis showed that FET implantation was associated with a low incidence of AKI (odds ratio: 0.28, 95% confidence interval: 0.08-0.96; p = 0.043). Among the 125 patients with or without RA abnormalities, no predictor of AKI was identified. CONCLUSION: FET implantation protected against postoperative AKI in patients with ATAAD extension into the RA.


Assuntos
Injúria Renal Aguda , Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Dissecção Aórtica/etiologia , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/métodos , Humanos , Masculino , Artéria Renal/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
4.
Ann Vasc Dis ; 15(1): 37-44, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35432643

RESUMO

Objective: To examine early histologic changes in the aorta exposed to bicuspid flow. Material and Methods: A porcine bicuspid aortopathy model was developed by suturing aortic cusps. Of nine pigs, eight underwent sham surgery (n=3) or bicuspidalization (n=5); one was used as an intact control. Wall shear stress (WSS) was assessed by computational fluid dynamics (CFD). Animals were exposed to normal or bicuspid flow for 48 h and were then euthanized for histologic examinations. Results: No animal died intraoperatively. One animal subjected to bicuspidalization died of respiratory failure during postoperative imaging studies. Echocardiography showed the aortic valve area decreased from 2.52±1.15 to 1.21±0.48 cm2 after bicuspidalization, CFD revealed increased maximum WSS (10.0±5.2 vs. 54.0±25.7 Pa; P=0.036) and percentage area of increased WSS (>5 Pa) in the ascending aorta (30.3%±24.1% vs. 81.3%±13.4%; P=0.015) after bicuspidalization. Hematoxylin-eosin staining and transmission electron microscopy showed subintimal edema and detached or degenerated endothelial cells following both sham surgery and bicuspidalization, regardless of WSS distribution. Conclusion: A bicuspid aortic valve appears to increase aortic WSS. The endothelial damage observed might have been related to non-pulsatile flow (cardiopulmonary bypass). Chronic experiments are needed to clarify the relationship between hemodynamic stress and development of bicuspid aortopathy.

5.
J Card Surg ; 37(7): 2194-2196, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35438808

RESUMO

BACKGROUND: The left subclavian artery (LSCA) is deeply located and difficult to visualize in some cases of total arch replacement. AIMS: We report an end-to-side anastomosis technique that enables safer and easier anatomical reconstruction of the LSCA. MATERIALS AND METHODS: Under Hypothermic circulatory arrest, the origin of the LSCA was ligated and pulled caudally. With clamping the distal LSCA, a graft was anastomosed to the anterior wall of the LSCA and antegrade cerebral perfusion to the LSCA was ensured through the anastomosed graft. Thereafter, distal anastomosis was performed proximal to the LSCA. RESULTS: The postoperative course was uneventful. DISCUSSION: Our reconstruction technique provides excellent exposure of the LSCA by pulling the origin of the LSCA caudally. Hemostasis after reconstruction is feasible, as the anastomosis in the anterior wall of the LSCA is easily visualized. CONCLUSION: The end-to-side anastomosis technique for LSCA reconstruction is a simple alternative in arch repair.


Assuntos
Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Anastomose Cirúrgica , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/métodos , Humanos , Artéria Subclávia/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos
6.
Artigo em Inglês | MEDLINE | ID: mdl-35170721

RESUMO

Distal stent graft-induced new entry is not rare after frozen elephant trunk implantation. We report a case of covered frozen elephant trunk placement for prevention of distal stent graft-induced new entry. Coverage of the rigid distal stent edge using a graft reduces mechanical stress on the intima and radial force of the distal stent; therefore, this technique can potentially prevent distal stent graft-induced new entry.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/métodos , Humanos , Stents , Resultado do Tratamento
7.
Eur J Cardiothorac Surg ; 61(5): 1077-1084, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-34849682

RESUMO

OBJECTIVES: Although a tear-oriented strategy has contributed to improving short-term surgical outcomes of acute type A aortic dissection (ATAAD), long-term clinical influences of residual entry tear in the downstream aorta have not been fully investigated. The goal of this study was to assess the long-term surgical outcomes of ATAAD with or without a residual entry tear in the downstream aorta. METHODS: Medical records of 1107 patients with ATAAD who underwent emergency surgery between 1990 and 2018 were retrospectively reviewed. A tear-oriented paradigm was adopted for the baseline strategy. The 837 patients in whom the entry tears were resected comprised the resected group, and the 270 patients with a residual entry tear comprised the residual group. Of these patients, 252 in each group were analysed using propensity score matching, and long-term outcomes were compared with or without residual entry. RESULTS: Hospital deaths were lower in the resected group (3.2% vs 8.3%; P = 0.020). The survival rate was not significantly different between the groups: It was 83.8% and 68.5% in the resected group and 80.2% and 66.5% in the residual group at 5 and 10 years, respectively (P = 0.600). However, residual entry in the downstream aorta affected the distal aortic event-free survival rate (90.4% and 80.6% in the resected group and 82.3% and 67.4% in the residual group at 5 and 10 years, respectively; P = 0.003). Furthermore, multivariable risk analysis of 1107 patients confirmed that a residual entry in the downstream aorta was a risk factor for distal aortic events. CONCLUSIONS: The tear-oriented strategy remains the gold standard for high-risk patients; however, the extensive operation might be considered for stable patients to reduce long-term aortic events.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Lacerações , Doença Aguda , Aorta Torácica/cirurgia , Implante de Prótese Vascular/efeitos adversos , Progressão da Doença , Humanos , Lacerações/etiologia , Lacerações/cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento
8.
Gen Thorac Cardiovasc Surg ; 69(2): 346-349, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32720243

RESUMO

A 38-year-old man underwent thoracic endovascular aortic repair for impending rupture of acute type B aortic dissection. Computed tomography revealed abscess formation around the proximal descending aorta 4 weeks after endovascular treatment. He underwent one-stage total arch and descending aorta replacement and omental wrapping via left thoracotomy. At the 6-month follow-up, his postoperative course was uneventful.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Adulto , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/efeitos adversos , Humanos , Masculino , Reimplante , Toracotomia , Resultado do Tratamento
9.
Eur J Cardiothorac Surg ; 59(4): 765-772, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33284961

RESUMO

OBJECTIVES: We investigated the outcomes of a fenestrated frozen elephant trunk (FET) technique performed without reconstruction of one or more supra-aortic vessels for aortic repair in patients with acute type A aortic dissection. METHODS: We investigated 22 patients who underwent the fenestrated FET technique for acute type A aortic dissection at our hospital between December 2017 and April 2020. The most common symptom was chest pain and/or back pain. Nine patients presented with malperfusion and 1 with cardiac arrest, preoperatively. A FET was deployed under hypothermic circulatory arrest and manually fenestrated under direct vision. Single fenestration was made in the FET in 15 patients, 2 fenestrations in 5 patients and a total fenestrated technique in 2 patients. Concomitant procedures were performed in 5 patients. RESULTS: The cardiopulmonary bypass, aortic cross-clamp and hypothermic circulatory arrest times were 181 ± 49, 106 ± 43 and 37 ± 7 min, respectively. In-hospital mortality, stroke, or recurrent nerve injury did not occur in any patient. One patient developed paraparesis, which completely recovered at discharge. During the follow-up period (mean 18 ± 7 months), 1 patient died of heart failure. Fenestration site occlusion did not occur. Follow-up computed tomography (mean 12 ± 6 months postoperatively) revealed that the maximal aortic diameter remained unchanged at the levels of the distal end of the FET, the 10th thoracic vertebra and the coeliac artery; however, the aortic diameter was significantly reduced at the level of the pulmonary artery bifurcation. CONCLUSIONS: The fenestrated FET technique is a simple, safe and effective procedure for selected patients with acute type A aortic dissection.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Humanos , Estudos Retrospectivos , Stents , Resultado do Tratamento
10.
Asian Cardiovasc Thorac Ann ; 28(9): 577-582, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32819152

RESUMO

BACKGROUND: Decision-making regarding the operability of thoracic aortic disease in nonagenarian patients remains controversial because outcomes of open surgical repair of the thoracic aorta are unclear. We investigated the surgical and nonsurgical outcomes of acute thoracic aortic syndrome treatment in nonagenarians. METHODS: After evaluating data in our institute from April 2016 to March 2020, we included 10 nonagenarians who needed surgical intervention on the thoracic aorta via a median sternotomy for acute thoracic aortic syndrome. The mean age of the cohort was 91.9 ± 2.1 years. Five patients underwent open surgical repair of the thoracic aorta (surgical group), and 5 refused surgery (nonsurgical group). All patients in the surgical group performed activities of daily living independently, with a mean clinical frailty scale of 3.2 ± 0.4. The surgical group included 4 patients with type A aortic dissection and one with a ruptured thoracic aortic aneurysm. Hemiarch replacement was performed in 3 patients and total arch replacement in 2. The mean follow-up period was 17.8 ± 5.1 months. RESULTS: Hospital mortality rates were 0% in the surgical and 80% in the nonsurgical group. The mean length of hospitalization was 28.4 ± 6.7 days in the surgical group. The 1-year survival rates were 100% in the surgical group and 20% in the nonsurgical group. CONCLUSION: Open surgical repair for acute thoracic aortic syndrome via median sternotomy is a reasonable treatment option even in nonagenarians. Involvement of family members is important for decision-making to devise the optimal treatment strategy (surgical vs. medical).


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Ruptura Aórtica/cirurgia , Implante de Prótese Vascular , Esternotomia , Fatores Etários , Idoso de 80 Anos ou mais , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/mortalidade , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/mortalidade , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/mortalidade , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Tomada de Decisão Clínica , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Seleção de Pacientes , Complicações Cognitivas Pós-Operatórias/mortalidade , Medição de Risco , Fatores de Risco , Esternotomia/efeitos adversos , Esternotomia/mortalidade , Síndrome , Fatores de Tempo , Resultado do Tratamento
12.
J Card Surg ; 35(2): 467-469, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31765018

RESUMO

BACKGROUND: An aortic pseudoaneurysm after cardiovascular surgery can be fatal. METHODS/RESULTS: Here, we describe the staged successful treatments of three pseudoaneurysms in a 77-year-old female patient who underwent total arch replacement and coronary artery bypass grafting 5 years ago. Computed tomography revealed three pseudoaneurysms: in the distal anastomosis of the total arch replacement, in the anastomosis of the left common carotid artery, and in the proximal anastomosis of the saphenous vein graft. Endovascular treatment and surgical repair were performed to treat these three pseudoaneurysms. DISCUSSION: An aortic pseudoaneurysm is a rare complication after cardiac or aortic surgery. Here, we present a case of combined endovascular and surgical repairs of three pseudoaneurysms in one patient.


Assuntos
Falso Aneurisma/cirurgia , Aorta Torácica/cirurgia , Doenças da Aorta/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares/métodos , Complicações Pós-Operatórias/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Idoso , Ponte de Artéria Coronária , Feminino , Humanos , Resultado do Tratamento
13.
Gen Thorac Cardiovasc Surg ; 67(12): 1007-1013, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31049816

RESUMO

OBJECTIVE: Postoperative atrial fibrillation (POAF) after open heart surgery is associated with a high risk of mortality and morbidity. Although oral ß-blockers are usually recommended to prevent POAF, the efficacy of a transdermal ß-blocker patch in preventing POAF is unclear. We compared the incidence of POAF between users of oral and transdermal bisoprolol. METHODS: We investigated 108 patients who underwent cardiac and/or thoracic aortic surgery between April 2016 and February 2018. We compared perioperative clinical and hemodynamic variables between 49 patients treated with a transdermal bisoprolol patch and 59 patients treated with an oral bisoprolol fumarate. RESULTS: POAF occurred in 24% of patients in the transdermal and in 46% of patients in the oral bisoprolol groups (p = 0.027). No intergroup difference was observed in in-hospital mortality, perioperative blood pressures and heart rates, and other morbidities. Multivariable logistic regression analysis revealed that the use of transdermal bisoprolol was independently associated with a lower rate of POAF (odds ratio 0.21, 95% confidence interval 0.05-0.84, p = 0.027). CONCLUSIONS: A transdermal bisoprolol patch is an effective and safe ß-blocker drug delivery system. The incidence of POAF in this group was lower than that in users of oral bisoprolol.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Fibrilação Atrial/epidemiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Administração Oral , Idoso , Fibrilação Atrial/tratamento farmacológico , Bases de Dados Factuais , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Adesivo Transdérmico
16.
J Thorac Cardiovasc Surg ; 157(3): 1071-1079.e3, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30139644

RESUMO

OBJECTIVE: Sarcopenia, age-related loss of muscle mass, is an objective and comprehensive marker of frailty. We aimed to clarify the influence of sarcopenia on the outcomes after heart valve surgery. METHODS: We retrospectively reviewed 1119 patients who underwent valve surgery via median sternotomy at our institution from June 2009 to December 2013. Patients aged <70 years, urgent/emergent cases, and patients without preoperative computed tomography of the abdomen were excluded. The remaining 428 patients were included in this study. Psoas muscle area, a validated measure of sarcopenia, was measured on preoperative computed tomography. Sarcopenia was defined as the lowest sex-specific quartile in psoas muscle area. The mean follow-up period was 3.4 years. RESULTS: Overall in-hospital mortality did not differ between the sarcopenia and nonsarcopenia patient groups. However, the incidence of stroke and intra-aortic balloon pump/percutaneous cardiopulmonary support use was greater in the sarcopenia group than in the nonsarcopenia group. The patients with sarcopenia had significantly decreased long-term survival and decreased freedom from major adverse cardiac and cerebrovascular events. Multivariable analysis and inverse probability weighting revealed that sarcopenia was an independent predictor for decreased survival (hazard ratio, 2.22; 95% confidence interval, 1.26-3.92; P = .006). CONCLUSIONS: Preoperative sarcopenia defined from the psoas muscle area was associated with long-term outcomes after valve surgery. Thus, the measurement of psoas muscle area can help facilitate more accurate risk scoring in elderly patients.

17.
Interact Cardiovasc Thorac Surg ; 28(3): 499-501, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30289458

RESUMO

Ventricular septal rupture is an uncommon fatal complication of acute myocardial infarction. In rare cases, the rupture can extend into the right ventricular free wall and cause intramyocardial dissection. We describe the case of a patient who developed postinfarction right ventricular free wall dissection with left-to-right shunting and successfully underwent patch repair.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Ruptura Cardíaca Pós-Infarto/diagnóstico , Ventrículos do Coração/diagnóstico por imagem , Idoso de 80 Anos ou mais , Angiografia Coronária , Ecocardiografia , Feminino , Ruptura Cardíaca Pós-Infarto/cirurgia , Ventrículos do Coração/cirurgia , Humanos , Tomografia Computadorizada por Raios X
19.
Ann Thorac Surg ; 105(1): 137-143, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29054307

RESUMO

BACKGROUND: Although surgical outcomes of acute type A aortic dissection (ATAAD) have improved, it is still a high-risk procedure for octogenarians. This study analyzed early and late outcomes of surgical repair of ATAAD among octogenarians. METHODS: From 1990 through 2016, 1,260 consecutive patients with ATAAD were emergently admitted to Jichi Medical University Hospitals. Of them, 1,026 patients who underwent emergency surgery for ATAAD within 48 hours of symptom onset were included in this retrospective study. Of these, 112 were aged 80 years or more (mean, 83.1 ± 2.7) and formed the octogenarian group; and 914 were aged less than 80 years (mean, 62.0 ± 11.4) and formed the control group. Early and late outcomes were compared. RESULTS: The inhospital mortality rate was 6.3% for the octogenarian group and 7.4% for the control group (p = 0.85). No significant difference was observed in the causes of hospital death. Although the overall postoperative complication rate was not different (24.1% versus 23.0%), pneumonia was more frequent among octogenarians (p = 0.03). Multivariate analysis of hospital mortality did not indicate age 80 years or more as a risk factor. Overall postoperative survival for the octogenarian group was 84.6%, 70.5%, and 57.1% at 1, 3, and 5 years, respectively. For the control group, the rates were 89.1%, 85.6%, and 82.1%, respectively. Pneumonia and decrepitude were the major causes of remote death for the octogenarian group. CONCLUSIONS: No significant difference in the hospital mortality rate or the complication rate was observed between the groups. Emergency surgery for ATAAD in octogenarians could be performed with the same low risk observed for younger patients.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Doença Aguda , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Dissecção Aórtica/classificação , Aneurisma da Aorta Torácica/classificação , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
20.
Am J Physiol Lung Cell Mol Physiol ; 314(1): L93-L106, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28882814

RESUMO

We recently demonstrated that blue light induces vasorelaxation in the systemic mouse circulation, a phenomenon mediated by the nonvisual G protein-coupled receptor melanopsin (Opsin 4; Opn4). Here we tested the hypothesis that nonvisual opsins mediate photorelaxation in the pulmonary circulation. We discovered Opsin 3 (Opn3), Opn4, and G protein-coupled receptor kinase 2 (GRK2) in rat pulmonary arteries (PAs) and in pulmonary arterial smooth muscle cells (PASMCs), where the opsins interact directly with GRK2, as demonstrated with a proximity ligation assay. Light elicited an intensity-dependent relaxation of PAs preconstricted with phenylephrine (PE), with a maximum response between 400 and 460 nm (blue light). Wavelength-specific photorelaxation was attenuated in PAs from Opn4-/- mice and further reduced following shRNA-mediated knockdown of Opn3. Inhibition of GRK2 amplified the response and prevented physiological desensitization to repeated light exposure. Blue light also prevented PE-induced constriction in isolated PAs, decreased basal tone, ablated PE-induced single-cell contraction of PASMCs, and reversed PE-induced depolarization in PASMCs when GRK2 was inhibited. The photorelaxation response was modulated by soluble guanylyl cyclase but not by protein kinase G or nitric oxide. Most importantly, blue light induced significant vasorelaxation of PAs from rats with chronic pulmonary hypertension and effectively lowered pulmonary arterial pressure in isolated intact perfused rat lungs subjected to acute hypoxia. These findings show that functional Opn3 and Opn4 in PAs represent an endogenous "optogenetic system" that mediates photorelaxation in the pulmonary vasculature. Phototherapy in conjunction with GRK2 inhibition could therefore provide an alternative treatment strategy for pulmonary vasoconstrictive disorders.


Assuntos
Quinase 2 de Receptor Acoplado a Proteína G/antagonistas & inibidores , Hipertensão Pulmonar/radioterapia , Fototerapia , Artéria Pulmonar/efeitos da radiação , Opsinas de Bastonetes/fisiologia , Vasodilatação/efeitos da radiação , Animais , Células Cultivadas , Quinase 2 de Receptor Acoplado a Proteína G/genética , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/patologia , Hipóxia/complicações , Luz , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efeitos da radiação , Óxido Nítrico/metabolismo , Artéria Pulmonar/citologia , Artéria Pulmonar/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Guanilil Ciclase Solúvel/genética , Guanilil Ciclase Solúvel/metabolismo , Vasodilatação/fisiologia
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