RESUMEN
BACKGROUND: The extracellular matrix plays an important role in heart valve function. To improve the processing of porcine pulmonary valves for clinical use, we have studied the influence of cryopreservation, decellularization, and irradiation on extracellular matrix components. METHODS: Decellularization was carried out followed by DNAseI/RNAseA digestion and isotonic washout. Valves were cryopreserved in 10% DMSO/10% fetal bovine serum, and then subjected to 25-40 kGy γ-radiation. Extracellular matrix constituents were evaluated by histologic staining, immunohistochemistry, transmission electron microscopy, and liquid chromatography/mass spectrometry. RESULTS: Histologic, immunohistochemical, ultrastructural, and biochemical analyses demonstrated a marked reduction in the expression of extracellular matrix components particularly in the valves that had been γ-irradiated following decellularization and cryopreservation. In this group, histology and immunohistochemistry showed an obvious reduction in staining for chondroitin sulphates, versican, hyaluronan, and collagens. Transmission electron microscopy revealed the smallest fibril diameter of collagen, shortest D-period, and loss of compactness of collagen fiber packaging and fragmentation of elastic fibers. Biochemical analysis showed loss of collagen and elastin crosslinks. Decellularization followed by cryopreservation showed some reduction in staining for collagens and versican, smaller diameter, shorter D-period in collagen fibers, and ridges in elastic fibers. Cryopreservation alone showed minimal changes in ECM staining intensity, collagen, and elastin ultrastructure and biochemistry. CONCLUSION: γ-Irradiated valves that have been decellularized and cryopreserved produces significant changes in the expression of ECM components, thus providing useful information for improving valve preparation for clinical use and also some indication as to why irradiated human heart valves were not clinically successful.
Asunto(s)
Criopreservación/métodos , Matriz Extracelular/efectos de la radiación , Rayos gamma/efectos adversos , Válvula Pulmonar/efectos de la radiación , Válvula Pulmonar/trasplante , Animales , Colágeno/metabolismo , Seno Coronario/efectos de la radiación , Seno Coronario/ultraestructura , Reactivos de Enlaces Cruzados/metabolismo , Elastina/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/ultraestructura , Glicosaminoglicanos/metabolismo , Humanos , Espectrometría de Masas , Microscopía Electrónica de Transmisión , Miocitos del Músculo Liso/efectos de la radiación , Miocitos del Músculo Liso/ultraestructura , Válvula Pulmonar/ultraestructura , Porcinos , Trasplante Heterólogo , Versicanos/metabolismoRESUMEN
BACKGROUND: With the increasing population of patients with prior mediastinal irradiation, cardiac surgeons will encounter patients with radiation-induced damage to the heart and the great vessels. Awareness of the pathology and the surgical management is essential to provide optimal care for these patients. METHODS: Eight patients with radiation-induced heart disease were encountered in the last 10 years. After a brief clinical presentation, the surgical management of radiation-induced heart disease is reviewed. RESULTS: Radiation can affect all the structures in the heart, including the coronary arteries, the valves, and the conduction system. The pericardium is the most commonly involved, and the conduction system is the least involved. Pericardiectomy is quite effective in patients with symptomatic pericardial effusion or constriction. The coronary lesions are located predominantly in the ostial or proximal regions of the epicardial vessels. Percutaneous transluminal coronary angioplasty alone appears to have a high rate of restenosis. Surgical revascularization has good long-term results, and the internal mammary artery should be used if it is satisfactory. The aortic and mitral valves are more commonly involved than the tricuspid and pulmonary valves. Myocardial dysfunction predominantly affects the right ventricle and requires particular attention during cardiopulmonary bypass and in the postoperative period. Restoration of sinus rhythm is essential in view of stiffness of the ventricles. Flexibility in the surgical approach with selective use of thoracotomy will facilitate the surgical procedure in certain patients. CONCLUSIONS: Surgeons should be well versed in all the manifestations and the management of radiation-induced heart disease.
Asunto(s)
Cardiopatías/cirugía , Traumatismos por Radiación/cirugía , Adulto , Anciano , Angioplastia Coronaria con Balón , Válvula Aórtica/efectos de la radiación , Válvula Aórtica/cirugía , Arritmias Cardíacas/etiología , Arritmias Cardíacas/cirugía , Puente Cardiopulmonar , Enfermedad Coronaria/etiología , Enfermedad Coronaria/cirugía , Enfermedad Coronaria/terapia , Vasos Coronarios/efectos de la radiación , Femenino , Sistema de Conducción Cardíaco/efectos de la radiación , Cardiopatías/etiología , Enfermedades de las Válvulas Cardíacas/etiología , Enfermedades de las Válvulas Cardíacas/cirugía , Humanos , Anastomosis Interna Mamario-Coronaria , Estudios Longitudinales , Masculino , Neoplasias del Mediastino/radioterapia , Persona de Mediana Edad , Válvula Mitral/efectos de la radiación , Válvula Mitral/cirugía , Planificación de Atención al Paciente , Derrame Pericárdico/etiología , Derrame Pericárdico/cirugía , Pericardiectomía , Pericarditis Constrictiva/etiología , Pericarditis Constrictiva/cirugía , Pericardio/efectos de la radiación , Válvula Pulmonar/efectos de la radiación , Traumatismos por Radiación/etiología , Radioterapia/efectos adversos , Recurrencia , Neoplasias Torácicas/radioterapia , Toracotomía , Resultado del Tratamiento , Válvula Tricúspide/efectos de la radiación , Disfunción Ventricular Derecha/etiología , Disfunción Ventricular Derecha/cirugíaRESUMEN
It is well known that radiation therapy to the anterior mediastinum may induce lesions of all cardiac structures. The pericardium is most frequently involved, but atrioventricular conduction disorders, cardiomyopathy, coronary stenosis may also be produced. Aortic, mitral and tricuspid lesions have been described. However, clinical evidence of pulmonic valve involvement has not been reported. Only at necropsy has fibrotic thickening of the pulmonic cusps occasionally been found. We report a case of infective endocarditis of the pulmonic valve in a 53-year-old patient who had undergone thoracic radiation therapy for Hodgkin's disease 31 years previously. Four years prior to the endocarditis he had also been submitted to myocardial revascularisation for critical lesions of the left main and right coronary ostia, and to aortic valve replacement because of stenosis and insufficiency. At that time, the pulmonic valve was fibrotic on echo examination. It is noteworthy that, of all the cardiac valves, the infective process involved only the pulmonic one, which is seldom the target of an infection. To our knowledge this is the first case of bacterial endocarditis of a heart valve that had been previously damaged by radiation therapy.
Asunto(s)
Endocarditis Bacteriana/etiología , Enfermedad de Hodgkin/radioterapia , Válvula Pulmonar/efectos de la radiación , Radioterapia/efectos adversos , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Enfermedad Coronaria/cirugía , Ecocardiografía Doppler , Endocarditis Bacteriana/diagnóstico por imagen , Prótesis Valvulares Cardíacas , Humanos , Masculino , Persona de Mediana Edad , Revascularización Miocárdica , Factores de TiempoRESUMEN
A case of infundibular pulmonary stenosis occurring years after a mediastinal radiation for Hodgkin's disease is reported. As far as the literature is known to us, a similar case has not yet been described. It is most likely that the development of the stenosis is due to the radiation therapy, since a murmur was not heard before radiation and a mild stenosis was proved several years after radiation. Now, a high gradient with the typical signs of an infundibular pulmonary stenosis was present. Unfortunately the patient refused the operation. Further possibilities for acquired pulmonary stenosis and cardial complications after mediastinal radiation for Hodgkin's disease will be discussed.