Assuntos
Cirurgia Torácica/história , Alemanha , História do Século XX , História do Século XXI , HumanosRESUMO
BACKGROUND/OBJECTIVES: The number of adult congenital heart disease (ACHD) patients will be larger in the medium to long term than that of children and adolescents with congenital heart disease. The present structures for the medical care of ACHD patients are not sufficient and need to be improved. Therefore the task force's assignment and objective was to develop recommendations for the structure of the interdisciplinary medical care of adults with congenital heart disease (GUCH). METHODS: The members of the interdisciplinary task force were selected on the basis of their special clinical, scientific and organizational expertise. Initially, a sub-group of the interdisciplinary task force compiled a draft version of these recommendations, with reference to international recommendations. It was circulated and then agreed with all task force members in two joint meetings. The recommendations were then submitted to the relevant committees of all participating societies and groups and approved following detailed discussion. RESULTS: With the publication of this document the interdisciplinary task force considers its first task as completed. CONCLUSIONS: The compiled recommendations for the structure of the interdisciplinary medical care of adults with congenital heart disease (GUCH) should ensure that the structural and medical pre-conditions for comprehensive GUCH medical care are created.
Assuntos
Cardiopatias Congênitas/terapia , Equipe de Assistência ao Paciente/normas , Guias de Prática Clínica como Assunto/normas , Qualidade da Assistência à Saúde/normas , Adulto , Fatores Etários , Cardiopatias Congênitas/diagnóstico , Humanos , Equipe de Assistência ao Paciente/tendências , Qualidade da Assistência à Saúde/tendênciasRESUMO
BACKGROUND: The number of adult congenital heart disease (ACHD) patients will be larger in the medium to long term than that of children and adolescents with congenital heart disease. The present structures for the medical care of ACHD patients are not sufficient and need to be improved. Therefore the Task Force aimed at developing recommendations for adult and paediatric cardiologists to acquire the additional qualification "Adults with Congenital Heart Disease" (ACDH). METHODS: The members of the interdisciplinary Task Force were selected on the basis of their special clinical, scientific and organisational expertise. The leading author submitted a draft version, which was revised by a sub-group of the interdisciplinary Task Force. It was subsequently agreed upon and re-circulated by all the members of the Task Force. The recommendations were then presented to the relevant committees of all participating associations and groups and approved following detailed discussion. RESULTS: A training programme for acquiring an additional qualification in the treatment of adults with congenital heart disease was created successfully. CONCLUSIONS: The medical care of adults with congenital heart disease is a sub-speciality in the border area between adult cardiology and paediatric cardiology. ACHD cardiologists are to be specially trained experts with appropriate knowledge and special skills and experience in the diagnosis and therapy of congenital heart disease in adults. ACHD cardiologists should be able to recognise and treat problems that occur in adulthood in connection with congenital heart disease.
Assuntos
Comitês Consultivos/normas , Cardiologia/normas , Cardiopatias Congênitas/terapia , Pediatria/normas , Médicos/normas , Guias de Prática Clínica como Assunto/normas , Cardiologia/educação , Necessidades e Demandas de Serviços de Saúde/normas , Cardiopatias Congênitas/diagnóstico , Humanos , Pediatria/educação , Recursos HumanosRESUMO
BACKGROUND: Long-segment tracheobronchial malacia may cause life-threatening dysfunction of the airway system at different levels. This study presents the long-term follow-up (1992 through 2008) of patients who received surgical treatment with external tracheal stabilization in our institution. METHODS: Eleven patients fulfilled the inclusion criteria. In surviving patients who presented for reexamination, pulmonary function testing, ergometry, and magnetic resonance imaging (MRI) were performed. RESULTS: All patients could be weaned from the ventilator and discharged. Patients were aged a median 11 months (range, 3 to 48 months) at operation for tracheal compression. Age at follow-up was 9.1 years (range, 0.5 to 16.3 years). Median follow-up was 7.3 years (range, 0.1 to 15.1 years). Postoperatively, 1 patient was lost to follow-up, and 4 died at 2.6 years (range, 0.5 to 6.6 years) of comorbidities. Pulmonary function testing showed a moderate residual airflow restriction, with maximal vital capacity at 75% of normal (range, 45% to 92%). Treadmill exercise testing demonstrated 70% to 89% of the expected normal values for age. Magnetic resonance imaging examination confirmed tracheal patency, but the lumen of the left main bronchus in 2 patients was 50% smaller than on the right. Diaphragmatic motion was normal in all patients. CONCLUSIONS: Children with congenital tracheal stenosis benefit from external tracheal stabilization. Survival in patients after external tracheal stabilization is significantly influenced by concomitant conditions.
Assuntos
Próteses e Implantes , Traqueia , Traqueomalácia/congênito , Traqueomalácia/cirurgia , Broncoscopia , Pré-Escolar , Teste de Esforço , Feminino , Seguimentos , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Politetrafluoretileno , Testes de Função Respiratória , Traqueomalácia/diagnóstico , Traqueomalácia/fisiopatologiaRESUMO
BACKGROUND: We present a group of infants and children with pulmonary arterial sling and tracheal stenosis. In some of the patients, the anomalously located pulmonary artery had previously been reimplanted, but without simultaneous repair of the trachea. METHODS: From 1992 to 2007, we reimplanted the left pulmonary artery in 13 children with a pulmonary arterial sling. Their median age was 8 months, with a range from 1 to 72 months. We also performed tracheal resection with end-to-end anastomosis, or complex tracheal reconstructions. In 5 patients, the reoperation was indicated because of persistent tracheal stenosis not treated initially at first correction of the arterial sling. All patients presented with stridor and respiratory distress. Cardiac catheterization, bronchoscopy and multidetecting computer tomography angiography were performed in all cases prior to the operation. All operations were performed under cardiopulmonary bypass. RESULTS: There was no operative or late mortality. The patients were extubated under bronchoscopic control. The mean period of intubation was 18 plus or minus 8 days, and the average follow-up was 8 plus or minus 4 years. The patients showed no signs of tracheal re-stenosis clinically or on bronchoscopy. The group of the patients under reoperations, however, required longer periods of intubation and hospitalization. CONCLUSION: Our experience demonstrates that, in patients with a pulmonary arterial sling, any associated tracheal stenosis should be explored at the initial operation, since decompression of the trachea by reimplanting the anomalously located pulmonary artery fails to provide relief. The funnel trachea, if present, undergoes progressive stenosis, and will require surgical repair. The use of cardiopulmonary bypass permitted extensive mobilization of the tracheobronchial tree, and allowed us to perform a tension-free anastomotic reconstruction of the trachea.
Assuntos
Artéria Pulmonar/anormalidades , Artéria Pulmonar/cirurgia , Estenose Traqueal/etiologia , Estenose Traqueal/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Reoperação , SíndromeRESUMO
AIMS: The EuroSCORE has been proposed to identify patients at high risk for surgical aortic valve replacement (AVR) and estimate for them the risk-benefit of percutaneous valve replacement. The aim of our study was to investigate the validity of this proposal. METHODS AND RESULTS: From 1994 to March 2006, 1545 consecutive patients with aortic stenosis underwent isolated surgical AVR at the Department of Cardiac Surgery of Heidelberg. Both additive and logistic EuroSCOREs were calculated for each patient and summed for expected 30-day mortality. Expected and observed mortalities were compared, particularly with respect to 'high-risk' status and era of operation. Overall, 30-day mortality was low (34/1545, 2.2%) and substantially overestimated by both additive (6.1%) and logistic (9.3%) EuroSCOREs. Although both EuroSCOREs stratified patients monotonically with respect to mortality risk, high-risk patients had a 3.6% mortality (29/833), whereas additive and logistic EuroSCOREs predicted 8.3 and 14.8%. Indeed, none of the 71 patients with a EuroSCORE of 11-20 (extremely high risk) died. The more recent the era of operation, the more pronounced was the discrepancy between expected and observed mortalities. CONCLUSION: Although the EuroSCORE still successfully stratifies patients undergoing surgical AVR relative to 30-day mortality, it has become increasingly uncalibrated with absolute risk, resulting in overestimation of 30-day mortality. Inaccurately predicted mortality, especially in 'high-risk' patients, renders it unsuitable for assessing risk reduction of percutaneous valve replacement.
Assuntos
Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Seleção de Pacientes , Idoso , Estenose da Valva Aórtica/mortalidade , Feminino , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/métodos , Implante de Prótese de Valva Cardíaca/mortalidade , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Medição de Risco/métodos , Medição de Risco/normas , Taxa de Sobrevida , Resultado do TratamentoAssuntos
Causas de Morte , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/mortalidade , Complicações Pós-Operatórias/mortalidade , Guias de Prática Clínica como Assunto , Bioprótese , Feminino , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/mortalidade , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Incidência , Masculino , Prognóstico , Falha de Prótese , Infecções Relacionadas à Prótese/mortalidade , Medição de Risco , Análise de SobrevidaRESUMO
Aortic root motion was previously identified as an additional risk factor for aortic dissection. This study analyzed if the magnitude of aortic root motion changed in patients after aortic valve replacement (AVR) and acute proximal aortic dissection. An institutional database (1984-2005) was used to measure the downward motion of the aortic root (perpendicular to the plane of the sinotubular junction) in contrast injections in 48 patients with aortic insufficiency (AI), aortic stenosis (AS) and proximal aortic dissection pre- and postoperatively, when available. Postoperative aortic root motion was significantly reduced after AVR for AI, while it was significantly increased after AVR for AS. By contrast, aortic root motion was unchanged when functional AI due to paravalvular leak was present post-AVR for AI. In patients with acute aortic dissection, both aortic root motion and aortic diameter were unchanged from pre-dissection. However, in patients who dissected again, aortic root motion was significantly smaller than pre-dissection, and the aortic diameter was significantly less than at first dissection. Removal of aortic stenosis was associated with increased aortic root motion, theoretically heightening the threat of dissection posed to the aortic wall by mechanical stress, although this was not confirmed by our study of dissection patients. Yet, mechanical principles command to include higher magnitude of aortic root motion during follow-up of patients after AVR as an additional risk factor for dissection.
Assuntos
Aneurisma Aórtico/cirurgia , Dissecção Aórtica/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Idoso , Dissecção Aórtica/etiologia , Dissecção Aórtica/fisiopatologia , Aneurisma Aórtico/etiologia , Aneurisma Aórtico/fisiopatologia , Valva Aórtica/fisiopatologia , Insuficiência da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/fisiopatologia , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Recidiva , Fatores de Tempo , Resultado do TratamentoRESUMO
A child with severe respiratory distress, previously operated on at age 4 months for pulmonary sling and atrial septal defect, underwent reoperation at age 4 years because of long-segment congenital tracheal stenosis complicated by an abnormal branching of the trachea-bridging bronchus. We review the anatomy of that rare pathomorphology and describe a slide tracheoplasty that uses the bridging bronchus for treatment of this complex anomaly.
Assuntos
Brônquios/cirurgia , Estenose Traqueal/cirurgia , Pré-Escolar , Humanos , Procedimentos Cirúrgicos Torácicos/métodos , Estenose Traqueal/patologiaRESUMO
BACKGROUND: We asked whether aortic valve replacement using a mechanical prosthesis would allow normalization of left ventricular function and structure in children and young adults. METHODS: We performed a clinical follow-up examination in 30 patients with aortic valve replacement at 25 years of age or younger, including conventional and tissue Doppler echocardiography and magnetic resonance imaging. RESULTS: Aortic valve replacement was performed at the median age of 14.3 years (range, 7.6 to 24.3 years) using a mechanical prosthesis (St. Jude Medical; median diameter, 23 mm; range, 17 to 27 mm). Indications were severe aortic stenosis in 6 of 30 patients, aortic regurgitation in 20 of 30 patients, or a combination of aortic stenosis and regurgitation (4 of 30 patients). Aortic valve replacement was a reoperation in 12 of 30 patients who primarily underwent aortic valvotomy at a median of 7.1 years (range, 1.0 to 11.3 years). In-hospital mortality was 0%. Follow-up was a median of 6 years (range, 1.2 to 14.5 years). Twenty-nine of 30 patients were in New York Heart Association functional class I without thromboembolic complications, cerebrovascular accidents, or major bleeding on oral anticoagulation. Left ventricular dilatation before aortic valve replacement was present in 20 of 30 patients but normalized in all but 4 patients on follow-up. Most patients showed a normal end-diastolic volume on magnetic resonance imaging, and 23 of 26 patients showed a normal left ventricular ejection fraction (median, 0.53; range, 0.33 to 0.75). Peak systolic strain of the left ventricular myocardium was a median of -13.3% (range, -0.5% to -31%), and was normal in 28 of 30 patients. CONCLUSIONS: Aortic valve replacement in children and young adults offers a good treatment option and may lead to normalization of left ventricular size and function in most patients.
Assuntos
Insuficiência da Valva Aórtica/diagnóstico , Insuficiência da Valva Aórtica/cirurgia , Bioprótese , Implante de Prótese de Valva Cardíaca/métodos , Adolescente , Adulto , Cateterismo Cardíaco , Ponte Cardiopulmonar , Criança , Estudos de Coortes , Ecocardiografia Doppler/métodos , Seguimentos , Humanos , Modelos Lineares , Imageamento por Ressonância Magnética/métodos , Probabilidade , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVE: Timing of the operation for exchange of right ventricular (RV) to pulmonary artery (PA) conduits is a matter of considerable debate. We aimed to study the course of right ventricular dimension in patients undergoing conduit exchange. PATIENTS AND METHODS: We retrospectively studied all patients who underwent implantation and or replacement of RV/PA conduits during the time period between 1990 and 2005. Clinical and echocardiographic data were recorded as obtained at follow-up visits. RESULTS: A total of 229 (144 boys and 85 girls) underwent surgery for implantation and or replacement of RV/PA conduits during the study period. Patients were assigned to three age groups including 37 infants, 125 children aged 1-10 years and 67 patients more than 10 years of age. 185 pulmonary (81%) and 44 aortic homografts (19%) were implanted. Fifty-eight of these 185 patients (25%) required exchange of conduits after a median time of 6.4 (8 months-12 years) (median (range)). The follow-up was 7.55 (0.1-17) years. The survival of the patients after homograft change was 98%. Freedom from failure for aortic and pulmonary homografts at an interval of 10 years for all patients was 38.5% for aortic and 56.2% for pulmonary homografts (P = 0.018; Mann-Whitney). Age at conduit exchange (coefficient: -4.917; P < 0.001) and right ventricular end-diastolic dimension (RVDD) before conduit exchange (coefficient: 8.255; P < 0.001) were related to RVDD as measured by M-mode echocardiography at follow-up ("best subset" regression analysis; R squared = 0.746). RVDD decreased in 48/58 patients, remained unchanged in 8/58 and increased in 2/59 patients at follow-up. An increased RVDD was positively correlated to the duration of artificial ventilation after the operation for conduit exchange (R = 0.56; P < 0.001). CONCLUSIONS: Reoperation for exchange of degenerated conduits should be performed early to prevent the development of irreversible structural myocardial changes and persistence of right ventricular dilatation.
Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Artéria Pulmonar/cirurgia , Obstrução do Fluxo Ventricular Externo/cirurgia , Adolescente , Antropometria/métodos , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/métodos , Criança , Pré-Escolar , Ventrículos do Coração/anatomia & histologia , Humanos , Lactente , Tempo de Internação , Estudos Longitudinais , Seleção de Pacientes , Artéria Pulmonar/diagnóstico por imagem , Reoperação , Respiração Artificial , Estudos Retrospectivos , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Ultrassonografia , Função Ventricular Direita , Obstrução do Fluxo Ventricular Externo/diagnóstico por imagemRESUMO
We studied the effect of chronic endothelin A receptor blockade by atrasentan on the pulmonary endothelin-1 system and vascular endothelial growth factor (VEGF) expression in piglets with high pulmonary blood flow. Twenty-five 4-week-old piglets with high pulmonary blood flow were randomized to three groups: sham operated (n = 8), placebo (water) (n = 7), or treatment with atrasentan (2 mg/kg per day) (n = 10). After 3 months, mean pulmonary arterial pressure (PAP) was higher in the placebo group than in the sham group [18 +/- 2 mm Hg versus 14 +/- 1 mm Hg; P < 0.05 (ANOVA)]. Atrasentan treatment was associated with lower cardiac output, PAP (14 +/- 1 mm Hg), and medial wall thickness of pulmonary arteries (diameter: 50-150 microM) compared with placebo [13.6 +/- 3.0% versus 18.1 +/- 4.2%; P < 0.05 (ANOVA)]. Quantitative real-time polymerase chain reaction for endothelin-1, endothelin B receptor, and endothelin-converting enzyme-1 mRNA in lung tissue did not differ. However, immunostaining as well as mRNA for VEGF were lower in atrasentan-treated animals (relative gene expression: atrasentan versus placebo: 0.8 +/- 0.3 versus 1.5 +/- 0.3; P = 0.009). Atrasentan treatment effectively reduces medial hypertrophy in piglets with chronic pulmonary hyperperfusion. Chronic endothelin A receptor blockade by atrasentan may interfere with the expression of VEGF.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Endotelina-1/antagonistas & inibidores , Hipertensão Pulmonar/tratamento farmacológico , Circulação Pulmonar , Pirrolidinas/farmacologia , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Animais , Atrasentana , Débito Cardíaco/efeitos dos fármacos , Doença Crônica , Modelos Animais de Doenças , Antagonistas do Receptor de Endotelina A , Endotelina-1/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hipertensão Pulmonar/fisiopatologia , Hipertrofia/tratamento farmacológico , Imuno-Histoquímica , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , RNA Mensageiro/metabolismo , Distribuição Aleatória , Receptor de Endotelina B/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Suínos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
In this model of pulmonary vascular disease, high pulmonary blood flow was created by an anastomosis between the left subclavian artery and the main pulmonary artery [Blalock-Taussig (BT) shunt] in 4-week-old piglets (n = 6). Additional ligation of the left pulmonary artery (LPA) was used to increase pulmonary artery pressure (n = 6). Seven piglets were sham-operated. After 3 months, mean pulmonary artery pressure was higher in animals with BT shunt and LPA ligation (22 +/- 5; mean+/-SD) compared to sham-operated animals (15 +/- 2). In addition, thickening of the medial coat (20.1 +/- 2.8% versus 13.6 +/- 3.1% wall thickness) and increased immunostaining for vascular endothelial growth factor A (VEGF-A) were observed. Relative gene expression for endothelin-converting enzyme-1 (ECE-1) mRNA was 1.8 times higher, and VEGF-A mRNA was 2.5 times higher in pigs with BT shunt and LPA ligation compared with sham-operated animals. VEGF receptor-1 and VEGF receptor-2 mRNA was lower in shunted animals and in animals with additional ligation of LPA. Upregulation of ECE-1 and VEGF-A, as well as changes in VEGFR expression in the pulmonary hypertensive lung, may contribute to pulmonary vascular changes.
Assuntos
Pressão Sanguínea , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Artéria Pulmonar/patologia , Circulação Pulmonar , Animais , Animais Recém-Nascidos , Ácido Aspártico Endopeptidases/genética , GMP Cíclico/sangue , Endotelina-1/sangue , Enzimas Conversoras de Endotelina , Hipertensão Pulmonar/metabolismo , Imuno-Histoquímica/métodos , Isoenzimas/genética , Pulmão/metabolismo , Metaloendopeptidases/genética , Nitratos/sangue , Nitritos/sangue , Artéria Pulmonar/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Coloração e Rotulagem , Suínos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND: Multiple wavelets and rotors are accused of maintaining atrial fibrillation (AF). However, snake-like excitation patterns have recently been observed in AF. So far, computer models have investigated AF in a simplified anatomical model. In this work, pulmonary vein firing is simulated to investigate the initiation and maintenance of AF in a realistic anatomical model. METHODS AND RESULTS: Thirty-five ectopic foci situated around all pulmonary veins were simulated by a unidirectional conduction block. The excitation propagation was simulated by an adaptive cellular automaton on a realistic 3-dimensional atrial anatomy. Atrial fibrillation was initiated in 65.7% of the simulations. Stable excitation patterns were broken up in anatomically heterogeneous regions, creating a streak-like excitation pattern similar to snakes. Multiple wavelets and rotors could be observed in anatomically smooth areas at the atria's roofs. CONCLUSIONS: The influence of macroscopic anatomical structures on the course of AF seems to play an important role in the excitation propagation in AF. The computer simulations indicate that multiple mechanisms contribute to the maintenance of AF.
Assuntos
Potenciais de Ação , Fibrilação Atrial/fisiopatologia , Relógios Biológicos , Mapeamento Potencial de Superfície Corporal/métodos , Sistema de Condução Cardíaco/fisiopatologia , Modelos Cardiovasculares , Veias Pulmonares/fisiopatologia , Simulação por Computador , HumanosRESUMO
PURPOSE: We investigated in a surgical rat model of vascular injury the potential role of the peroxynitrite - poly(ADPribose) polymerase (PARP) pathway in inflammatory response and apoptosis induction after vascular gamma irradiation. METHODS: Male Sprague-Dawley rats underwent left carotid endarterectomy with removal of intima: control (n = 10) and were irradiated with 15 Gray (n = 13) or 20 Gray (n = 10) postoperatively and compared with sham-operated rats (n = 10). Additional animals were solely irradiated with 15 Gy (n = 10) and with 20 Gy (n = 10) to distinguish between primary effects of vascular injury and secondary effects due to irradiation. RESULTS: After 21 days, neointima formation was significantly suppressed after irradiation (control: 0.07 mm(2) +/- 0.04 mm(2), 15 Gy: 0.003 mm(2) +/- 0.004 mm(2), 20 Gy: 0.001 mm(2) +/- 0.0006 mm(2), P< 0.0001). However, a significant inflammation of the vessel wall with focal wall necrosis was detected (control: 0.2 +/- 0.15, 15 Gy: 0.82 +/- 1.2, 20 Gy: 1.25 +/- 0.86, P= 0.003). Immunohistochemistry showed significant staining for nitrotyrosine, poly(ADP-ribose) and nuclear translocation of apoptosis-inducing factor in the neointima of the control group. In the irradiated groups these stainings were significantly higher in the media and adventitia compared to the non-irradiated groups. CONCLUSION: Activation of the peroxynitrite-PARP pathway was demonstrated during neointima proliferation in a rat model of surgical vascular injury. Vascular irradiation suppressed neointima formation, but induced significant activation of the peroxynitrite - PARP pathway in the outer vessel wall layers concomitant to inflammation and focal wall necrosis. This may contribute to adverse effects of vascular irradiation such as fibrosis and constrictive remodeling.
Assuntos
Apoptose/efeitos da radiação , Vasos Sanguíneos/efeitos da radiação , Raios gama/efeitos adversos , Poli(ADP-Ribose) Polimerases/metabolismo , Túnica Íntima/efeitos da radiação , Animais , Vasos Sanguíneos/lesões , Vasos Sanguíneos/patologia , Modelos Animais de Doenças , Endarterectomia das Carótidas/efeitos adversos , Imuno-Histoquímica , Masculino , Ácido Peroxinitroso/metabolismo , Lesões Experimentais por Radiação , Ratos , Ratos Sprague-Dawley , Túnica Íntima/lesões , Túnica Íntima/patologia , Doenças Vasculares/etiologiaRESUMO
PURPOSE: In a rat model of endarterectomy we investigated the potential role of the peroxynitrite-poly(ADP-ribose) polymerase (PARP) pathway in neointima formation and the effects of irradiation, pharmacologic inhibition of PARP, or combined pharmacologic inhibition of PARP and irradiation on vascular remodeling. METHODS AND MATERIALS: Carotid endarterectomy was performed by incision of the left carotid artery with removal of intima in Sprague-Dawley rats. Six groups were studied: sham-operated rats (n = 10), control endarterectomized rats (n = 10), or endarterectomized rats irradiated with 15 Gy (n = 10), or treated with PARP inhibitor, INO-1001 (5 mg/kg/day) (n = 10), or with combined treatment with INO-1001 and irradiation with 5 Gy (n = 10) or with 15 Gy (n = 10). After 21 days, neointima formation and vascular remodeling were assessed. RESULTS: Neointima formation after endarterectomy was inhibited by postoperative irradiation with 15 Gy and was attenuated by PARP inhibition. However, in parallel to inhibition of neointimal hyperplasia, activation of the peroxynitrite-PARP pathway in the outer vessel wall layers was triggered by postoperative irradiation. Combined pharmacologic PARP inhibition and irradiation with 15 Gy significantly reduced both neointimal hyperplasia and activation of the peroxynitrite-PARP pathway in the outer vessel wall layers. Combination of PARP inhibition and irradiation with 5 Gy was less effective than both PARP inhibition or irradiation with 15 Gy alone. CONCLUSIONS: We conclude, that combined PARP inhibition and irradiation with 15 Gy may be a new dual strategy for prevention of restenosis after surgical vessel reconstruction: combining the strong antiproliferative effect of irradiation and ameliorating irradiation-induced side effects caused by excessive PARP activation.