Hydrogen Sulfide Improves Cardiomyocyte Function in a Cardiac Arrest Model

[EN] Background: Cardioplegic arrest is a common procedure for many types of cardiac surgery, and different formulations have been proposed to enhance its cardio-protective effect. Hydrogen sulfide is an important signaling molecule that has cardio-protective properties. We therefore studied the cardio-protective effect of hydrogen sulfide in cardiac cell culture and its potential therapeutic use in combination with cardioplegia formulations. Materials/Methods: We added hydrogen sulfide donor GYY4137 to HL-1 cells to study its protective effect in nutrient starved conditions. In addition, we tested the potential use of GYY4137 when it is added into two different cardioplegia formulations: Cardi-Braun (R) solution and del Nido solution in an ex vivo Langendorff perfused rat hearts model. Results: We observed that eight-hour pre-treatment with GYY4137 significantly suppressed apoptosis in nutrient-starved HL-1 cells (28% less compared to untreated cells; p<0.05), maintained ATP content, and reduced protein synthesis. In ex vivo experiments, Cardi-Braun (R) and del Nido cardioplegia solutions supplemented with GYY4137 significantly reduced the pro-apoptotic protein caspase-3 content and preserved ATP content. Furthermore, GYY4137 supplemented cardioplegia solutions decreased the S-(5-adenosyl)-L-methionine/S-(adenosyl)-L-homocysteine ratio, reducing the oxidative stress in cardiac tissue. Finally, heart beating analysis revealed the preservation of the inter-beat interval and the heart rate in del Nido cardioplegia solution supplemented with GYY4137. Conclusions: GYY4137 preconditioning preserved energetic state during starved conditions, attenuating the cardiomyocytes apoptosis in vitro. The addition of GYY4137 to cardioplegia solutions prevented apoptosis, ATP consumption, and oxidative stress in perfused rat hearts, restoring its electrophysiological status after cardiac arrest. These findings suggested that GYY4137 sulfide donor may improve the cardioplegia solution performance during cardiac surgery.Instituto de Salud Carlos III grants (PI10/743, PI13/0414) and RETICS RD12/0019/0025 co-funded by FEDER "Una Manera de Hacer Europa". AG. acknowledges a fellowship from Erasmus Mundus Eurotango Program. ADJ acknowledges support from the Ramon y Cajal program (RYC-2008-02378). P.S. acknowledges support from PI10/743, PI13/414 grants and the Miguel Servet I3SNS and RETICS Program (RD12/0025). We thank Dr Kenneth McCreath for helpful comments on the manuscript.Garcia, NA.; Moncayo-Arlandi, J.; Vázquez Sánchez, A.; Genoves, P.; Calvo Saiz, CJ.; Millet Roig, J.; Martí, N.... (2017). Hydrogen Sulfide Improves Cardiomyocyte Function in a Cardiac Arrest Model. Annals of Transplantation. 22:285-295. https://doi.org/10.12659/AOT.901410S2852952

Reseñas iberoamericanas

Iberoamerican ReviewsReseñas iberoamericana

Cirugía de los aneurismas del arco aórtico

El aneurisma de arco aórtico (AAA) es la dilatación patológica que afecta a la porción horizontal de la aorta intratorácica. En el presente capítulo se analizan los principales aspectos relacionados con la historia natural y las complicaciones de esta enfermedad, fundamentalmente la rotura, así como los métodos diagnósticos, las indicaciones actuales de tratamiento quirúrgico según la evidencia disponible, la valoración del riesgo quirúrgico y el estudio preoperatorio necesario y las principale s variantes técnicas de tratamiento, tanto en cirugía abierta como híbrida

Asistencia mecánica circulatoria de corta duración

El manejo conservador con inotrópicos y vasopresores en el shock cardiogénico ha mostrado ser insuficiente en muchos pacientes para mantener una perfusión adecuada y prevenir el fallo multiorgánico irreversible, lo que ha llevado a la mejora y a la utilización cada vez mayor de diferentes dispositivos de asistencia mecánica circulatoria de corta duración (balón intraaórtico de contrapulsación, TandemHeart, Impella, oxigenación de membrana extracorpórea [ECMO] y CentriMag Levitronix). Por ser la ECMO el dispositivo más versátil —capaz de proporcionar soporte a pacientes con fallo cardíaco, fallo respiratorio o fallo combinado cardiopulmonar durante días a semanas—, sus indicaciones se han ido diversificando, con un uso e interés en adultos creciente durante los últimos años, gracias también al progreso tecnológico y a la mejora en sus resultados. Es por ello esencial familiarizarse con la fisiología, las indicaciones, las estrategias de canulación, los principios de manejo y la evidencia sobre esta terapia, en la que enfatizaremos especialmente en esta revisión

Hypoxia-inducible factor 1 alpha contributes to cardiac healing in mesenchymal stem cells-mediated cardiac repair

12 p.-6 fig.-1 tab.Mesenchymal stem cells (MSC) are effective in treating myocardial infarction (MI) and previous reports demonstrated that hypoxia improves MSC self-renewal and therapeutics. Considering that hypoxia-inducible factor- 1 alpha (HIF-1a) is a master regulator of the adaptative response to hypoxia, we hypothesized that HIF-1a overexpression in MSC could mimic some of the mechanisms triggered by hypoxia and increase their therapeutic potential without hypoxia stimulation. Transduction of MSC with HIF-1a lentivirus vectors (MSC-HIF) resulted in increased cell adhesion and migration, and activation of target genes coding for paracrine factors. When MSC-HIF were intramyocardially injected in infarcted nude rats, significant improvement was found (after treatment of infarcted rats with MSC-HIF) in terms of cardiac function, angiogenesis, cardiomyocyte proliferation, and reduction of fibrotic tissue with no induction of cardiac hypertrophy. This finding provides evidences for a crucial role of HIF-1a on MSC biology and suggests the stabilization of HIF-1a as a novel strategy for cellular therapies.This work was supported in part by grants from the Instituto de Salud Carlos III for the Regenerative Medicine Program of Valencian Community to Centro de Investigación Principe Felipe, KUTXA founding and from the FIS (PI07/784, CP08/80 and PI10/00743).Peer reviewe

III Registro Nacional del Procedimiento de Ross en España (2004)

Tras más de 10 años desde las primeras aplicaciones de la operación de Ross en España describimos el grado de implantación y sus resultados. Métodos: Anualmente los centros nacionales que realizan esta intervención envían sus datos al coordinador. Analizamos morbimortalidad, disfunción de auto y homoinjerto, y necesidad de reintervención. Resultados: Desde febrero de 1991 hasta mayo de 2004 se han incluido 281 pacientes. La etiología más frecuente fue la congénita (166, 59,4%). La insuficiencia aórtica fue el tipo de lesión predominante (126, 44,83%). Nueve (3,2%) pacientes requirieron balón de contrapulsación intraaórtico. La mortalidad a 30 días fue del 3,2% (n = 7). El seguimiento está completo en el 98,2%, con una media de 46,08 ± 33,09 meses (rango 1–159), estando el 28,89% (n = 84) de los pacientes seguidos más de 4 años. Respecto al estatus del autoinjerto, el 82,91% (233) se encuentra sin insuficiencia, presentando 12 (4,27%) insuficiencia moderada y cuatro (1,42%) insuficiencia grave (96,73 ± 1,2% libres de reintervención). El homoinjerto se encuentra normofuncionante o con disfunción leve en 255 pacientes (90,74%), presentando siete (2,49%) estenosis grave. Cuatro (1,42%) pacientes han requerido alguna reintervención sobre el tracto de salida del ventrículo derecho. La supervivencia a 48 meses es de 96,3 ± 1,05%. Conclusiones: 1. El número de pacientes incluidos de forma anual tiende a mantenerse y crecer. 2. El número de centros implicados continúa en aumento pero la mayor actividad se concentra en un grupo reducido de centros. 3. La morbimortalidad inicial es baja. 4. El índice de disfunción del homo y/o autoinjerto es aceptable

Heart failure induces significant changes in nuclear pore complex of human cardiomyocytes.

AIMS: The objectives of this study were to analyse the effect of heart failure (HF) on several proteins of nuclear pore complex (NPC) and their relationship with the human ventricular function. METHODS AND RESULTS: A total of 88 human heart samples from ischemic (ICM, n = 52) and dilated (DCM, n = 36) patients undergoing heart transplant and control donors (CNT, n = 9) were analyzed by Western blot. Subcellular distribution of nucleoporins was analysed by fluorescence and immunocytochemistry. When we compared protein levels according to etiology, ICM showed significant higher levels of NDC1 (65%, p<0.0001), Nup160 (88%, p<0.0001) and Nup153 (137%, p = 0.004) than those of the CNT levels. Furthermore, DCM group showed significant differences for NDC1 (41%, p<0.0001), Nup160 (65%, p<0.0001), Nup153 (155%, p = 0.006) and Nup93 (88%, p<0.0001) compared with CNT. However, Nup155 and translocated promoter region (TPR) did not show significant differences in their levels in any etiology. Regarding the distribution of these proteins in cell nucleus, only NDC1 showed differences in HF. In addition, in the pathological group we obtained good relationship between the ventricular function parameters (LVEDD and LVESD) and Nup160 (r = -0382, p = 0.004; r = -0.290, p = 0.033; respectively). CONCLUSIONS: This study shows alterations in specific proteins (NDC1, Nup160, Nup153 and Nup93) that compose NPC in ischaemic and dilated human heart. These changes, related to ventricular function, could be accompanied by alterations in the nucleocytoplasmic transport. Therefore, our findings may be the basis for a new approach to HF management

Heart failure induces significant changes in nuclear pore complex of human cardiomyocytes.

AIMS: The objectives of this study were to analyse the effect of heart failure (HF) on several proteins of nuclear pore complex (NPC) and their relationship with the human ventricular function. METHODS AND RESULTS: A total of 88 human heart samples from ischemic (ICM, n = 52) and dilated (DCM, n = 36) patients undergoing heart transplant and control donors (CNT, n = 9) were analyzed by Western blot. Subcellular distribution of nucleoporins was analysed by fluorescence and immunocytochemistry. When we compared protein levels according to etiology, ICM showed significant higher levels of NDC1 (65%, p<0.0001), Nup160 (88%, p<0.0001) and Nup153 (137%, p = 0.004) than those of the CNT levels. Furthermore, DCM group showed significant differences for NDC1 (41%, p<0.0001), Nup160 (65%, p<0.0001), Nup153 (155%, p = 0.006) and Nup93 (88%, p<0.0001) compared with CNT. However, Nup155 and translocated promoter region (TPR) did not show significant differences in their levels in any etiology. Regarding the distribution of these proteins in cell nucleus, only NDC1 showed differences in HF. In addition, in the pathological group we obtained good relationship between the ventricular function parameters (LVEDD and LVESD) and Nup160 (r = -0382, p = 0.004; r = -0.290, p = 0.033; respectively). CONCLUSIONS: This study shows alterations in specific proteins (NDC1, Nup160, Nup153 and Nup93) that compose NPC in ischaemic and dilated human heart. These changes, related to ventricular function, could be accompanied by alterations in the nucleocytoplasmic transport. Therefore, our findings may be the basis for a new approach to HF management

Heart Failure Induces Significant Changes in Nuclear Pore Complex of Human Cardiomyocytes

Aims: The objectives of this study were to analyse the effect of heart failure (HF) on several proteins of nuclear pore complex (NPC) and their relationship with the human ventricular function. Methods and results: A total of 88 human heart samples from ischemic (ICM, n = 52) and dilated (DCM, n = 36) patients undergoing heart transplant and control donors (CNT, n = 9) were analyzed by Western blot. Subcellular distribution of nucleoporins was analysed by fluorescence and immunocytochemistry. When we compared protein levels according to etiology, ICM showed significant higher levels of NDC1 (65%, p<0.0001), Nup160 (88%, p<0.0001) and Nup153 (137%, p = 0.004) than those of the CNT levels. Furthermore, DCM group showed significant differences for NDC1 (41%, p<0.0001), Nup160 (65%, p<0.0001), Nup153 (155%, p = 0.006) and Nup93 (88%, p<0.0001) compared with CNT. However, Nup155 and translocated promoter region (TPR) did not show significant differences in their levels in any etiology. Regarding the distribution of these proteins in cell nucleus, only NDC1 showed differences in HF. In addition, in the pathological group we obtained good relationship between the ventricular function parameters (LVEDD and LVESD) and Nup160 (r = -0382, p = 0.004; r = -0.290, p = 0.033; respectively). Conclusions: This study shows alterations in specific proteins (NDC1, Nup160, Nup153 and Nup93) that compose NPC in ischaemic and dilated human heart. These changes, related to ventricular function, could be accompanied by alterations in the nucleocytoplasmic transport. Therefore, our findings may be the basis for a new approach to HF management