Hydrogen Sulfide Improves Cardiomyocyte Function in a Cardiac Arrest Model

Fecha de publicación: 09/05/2017

Autores de IIS La Fe

• Nahuel Aquiles Garcia

  Autor

• Javier Moncayo Arlandi

  Autor

• Alejandro Vázquez Sánchez

  Autor

• José Millet

  Autor

• Nuria Marti Gutierrez

  Autor

• Cristina Aguado Codina

  Autor

• Iñigo Valiente Alandi

  Autor

• José Anastasio Montero Argudo

  Autor

• Antonio Diez Juan

  Autor

• 

  Pilar Sepúlveda Sanchis

  Autor

Participantes ajenos a IIS La Fe

• Genoves, P
• Calvo, CJ
• Knecht, E

Grupos

• Regeneración y Trasplante Cardíaco

  

  Leader

  Pilar Sepúlveda Sanchis

Abstract

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.

Keywords

• Cardiac Surgical Procedures; Cardioplegic Solutions; Hydrogen Sulfide