RESUMO
Homocysteine (Hcy) is an independent risk factor for endothelial dysfunction in cardiovascular diseases. We hypothesized that the eNOS transcription enhancer AVE3085 may protect the endothelial function damaged by Hcy in the human internal mammary artery (IMA). Cumulative concentration-relaxation curves to acetylcholine (-10 to -4.5 log mol/L) or sodium nitroprusside were established in IMA from patients undergoing coronary artery surgery precontracted by U46619 (-8 log mol/L) in the absence/presence of Hcy (100⯵mol/L) with/without AVE3085 (30⯵mol/L) in vitro in a myograph. RT-qPCR and ELISA were used to quantify the mRNA and protein levels of eNOS. Colorimetric assay method was used to detect the production of nitric oxide (NO). Maximal relaxation was significantly attenuated by Hcy in human IMA. Co-incubation with AVE3085 protected endothelium from the impairment by Hcy and increased the production of NO. Exposure to Hcy for 24â¯h downregulated eNOS protein expression (Pâ¯<â¯0.05) whereas it upregulated the expression of eNOS at mRNA levels (Pâ¯<â¯0.05). The presence of AVE3085 in addition to Hcy significantly increased the eNOS protein (Pâ¯<â¯0.05) and slightly decreased the mRNA level. The study for the first time revealed that in the human blood vessels (IMA) the clinically-relevant high concentration of Hcy directly causes endothelial dysfunction by downregulating eNOS protein that may be reversed by AVE3085. These findings not only provide new direction for protecting endothelium during coronary artery bypass grafting and improving long-term patency of the grafts, but also provide evidence to the use of eNOS enhancer in the patients with endothelial dysfunction in various pathological conditions.
Assuntos
Benzodioxóis/farmacologia , Endotélio Vascular/fisiopatologia , Homocisteína/metabolismo , Indanos/farmacologia , Artéria Torácica Interna/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Acetilcolina/farmacologia , Acetilcisteína/farmacologia , Endotélio Vascular/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Homocisteína/farmacologia , Humanos , Artéria Torácica Interna/fisiopatologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Nitroprussiato/farmacologia , Técnicas de Cultura de Órgãos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologiaRESUMO
The long-term patency rate of saphenous vein (SV) grafts is poor compared to arterial grafts. To investigate the effects of surgical preparation (distention) of SV on hydrogen sulfide (H2S) released from the endothelium, human SV segments were harvested from 43 patients during coronary artery bypass surgery (CABG). Acetylcholine (ACh) induced relaxation that was inhibited by NG-nitro-L-arginine + indomethacin and cysteine aminotransferase inhibitor aminooxyacetic acid in the normal SV. In contrast, ACh did not evoke relaxation in the distended SV (DSV). The concentration of H2S quantified by methylene blue assay in DSV was significantly lower than that in control. Transmission electron microscope and immunohistochemistry studies showed that the preparation destroyed the endothelium, smooth muscle, organelle, and vasa vasorum. We conclude that surgical preparation injures the endothelium and smooth muscle of the SV grafts and reduces H2S release from SV. These effects may contribute to the poor long-term patency of the SV graft.
Assuntos
Ponte de Artéria Coronária/efeitos adversos , Endotélio Vascular/transplante , Oclusão de Enxerto Vascular/etiologia , Sulfeto de Hidrogênio/metabolismo , Músculo Liso Vascular/transplante , Veia Safena/transplante , Coleta de Tecidos e Órgãos/efeitos adversos , Lesões do Sistema Vascular/etiologia , Idoso , Endotélio Vascular/lesões , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Oclusão de Enxerto Vascular/metabolismo , Oclusão de Enxerto Vascular/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/lesões , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/fisiopatologia , Veia Safena/lesões , Veia Safena/metabolismo , Veia Safena/fisiopatologia , Transdução de Sinais , Grau de Desobstrução Vascular , Lesões do Sistema Vascular/metabolismo , Lesões do Sistema Vascular/fisiopatologiaRESUMO
OBJECTIVES: The strategies of repair of tetralogy of Fallot change with the age of patients. In children older than 4 years and adults, the optimal strategy may be to use different method of reconstruction of the right ventricular outflow tract from those followed in younger children, so as to avoid, or reduce, the pulmonary insufficiency that is increasingly known to compromise right ventricular function. METHODS: From April, 2001, through May, 2008, we undertook complete repair in 312 patients, 180 male and 132 female, with a mean age of 11.3 years +/-0.4 years, and a range from 4 to 48 years, with typical clinical and morphological features of tetralogy of Fallot, including 42 patients with the ventriculo-arterial connection of double outlet right ventricle. The operation was performed under moderate hypothermia using blood cardioplegia. The ventricular septal defect was closed with a Dacron patch. When it was considered necessary to resect the musculature within the right ventricular outflow tract, or perform pulmonary valvotomy, we sought to preserve the function of the pulmonary valve by protecting as far as possible the native leaflets, or creating a folded monocusp of autologous pericardium. RESULTS: The repair was achieved completely through right atrium in 192, through the right ventricular outflow tract in 83, and through the right atrium, the outflow tract, and the pulmonary trunk in 36 patients. A transjunctional patch was inserted in 169 patients, non-valved in all but 9. There were no differences regarding the periods of aortic cross-clamping or cardiopulmonary bypass. Of the patients, 5 died (1.6%), with no influence noted for the transjunctional patch. Of those having a non-valved patch inserted, three-tenths had pulmonary regurgitation of various degree, while those having a valved patch had minimal pulmonary insufficiency and good right ventricular function postoperatively, this being maintained after follow-up of 8 to 24-months. CONCLUSIONS: Based on our experience, we suggest that the current strategy of repair of tetralogy of Fallot in older children and adults should be based on minimizing the insertion of transjunctional patches, this being indicated only in those with very small ventriculo-pulmonary junctions. If such a patch is necessary, then steps should be taken to preserve the function of the pulmonary valve.
Assuntos
Procedimentos Cirúrgicos Cardiovasculares/métodos , Pericárdio/transplante , Valva Pulmonar/cirurgia , Tetralogia de Fallot/cirurgia , Adolescente , Adulto , Fatores Etários , Ponte Cardiopulmonar , Procedimentos Cirúrgicos Cardiovasculares/efeitos adversos , Procedimentos Cirúrgicos Cardiovasculares/mortalidade , Criança , Pré-Escolar , China , Ecocardiografia Transesofagiana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polietilenotereftalatos , Tetralogia de Fallot/diagnóstico por imagem , Tetralogia de Fallot/fisiopatologia , Transplante Autólogo , Resultado do Tratamento , Função Ventricular Direita/fisiologia , Adulto JovemAssuntos
Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Endotélio Vascular/fisiologia , Sulfeto de Hidrogênio/farmacologia , Artéria Torácica Interna/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Vasodilatação/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Masculino , Artéria Torácica Interna/efeitos dos fármacos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Functional tricuspid regurgitation (TR) occurs in patients with rheumatic mitral valve disease even after mitral valve surgery. The aim of this study was to analyze surgical results of TR after previous successful mitral valve surgery. METHODS: From September 1996 to September 2008, 45 patients with TR after previous mitral valve replacement underwent second operation for TR. In those, 43 patients (95.6%) had right heart failure symptoms (edema of lower extremities, ascites, hepatic congestion, etc.) and 40 patients (88.9%) had atrial fibrillation. Twenty-six patients (57.8%) were in New York Heart Association (NYHA) functional class III, and 19 (42.2%) in class IV. Previous operations included: 41 for mechanical mitral valve replacement (91.1%), 4 for bioprosthetic mitral valve replacement (8.9%), and 7 for tricuspid annuloplasty (15.6%). RESULTS: The tricuspid valves were repaired with Kay's (7 cases, 15.6%) or De Vega technique (4 cases, 8.9%). Tricuspid valve replacement was performed in 34 cases (75.6%). One patient (2.2%) died. Postoperative low cardiac output (LCO) occurred in 5 patients and treated successfully. Postoperative echocardiography showed obvious reduction of right atrium and ventricle. The anterioposterior diameter of the right ventricle decreased to 25.5 ± 7.1 mm from 33.7 ± 6.2 mm preoperatively (P < 0. 05). CONCLUSION: TR after mitral valve replacement in rheumatic heart disease is a serious clinical problem. If it occurs or progresses late after mitral valve surgery, tricuspid valve annuloplasty or replacement may be performed with satisfactory results. Due to the serious consequence of untreated TR, aggressive treatment of existing TR during mitral valve surgery is recommended.