Contents

πŸ“’ Jones 2015

Quantification of the effects of electrical remodeling due to hypertrophic cardiomyopathy on human ventricular electromechanical activity and energetics1

Sciwheel

Introduction to Hypertrophic cardiomyopathy (HCM)

  • increased Ca2+ load
  • impairment of cytosolic ATPases
  • an increase in active Ca2+/calmodulin-dependent kinase II (CaMKII)
  • mitochondria are placed under strain leading to energetic impairment and an increase in reactive oxygen species (ROS) production.
  • Decreased PCr / ATP
  • Decrease in levels of NADPH (antioxidant capacity)

Methods

  • EP: O’Hara-Rudy (ORd) ventricular cell model
  • Contraction: metabolite sensitive formulation by Tran et al.:
  • mitochondrial energetics with ROS: Gauthier et al.
  • ATP and Cr shuttle: ECME model by Cortassa

https://user-images.githubusercontent.com/40054455/86698947-5682ab00-c042-11ea-8b42-8930e391bfec.png

https://user-images.githubusercontent.com/40054455/86698953-584c6e80-c042-11ea-90b6-931e22b6e257.png

Results

https://user-images.githubusercontent.com/40054455/86698955-58e50500-c042-11ea-80aa-562f41e24ba8.png

https://user-images.githubusercontent.com/40054455/86698965-5a163200-c042-11ea-96b9-5916358ebf16.png

  • 14% reduction of the PCr/ATP ratio
  • 26% decrease in mitochondrial NADPH

https://user-images.githubusercontent.com/40054455/86698973-5b475f00-c042-11ea-83e8-a225c52dcf34.png

Discussions

The effects increased Ca2+ sensitivity and electrical remodeling have on the contractile properties of the cell, energetics, and levels of ROS production

References


  1. Jones GM, Colman MA, Zhang H. Quantification of the effects of electrical remodeling due to hypertrophic cardiomyopathy on human ventricular electromechanical activity and energetics. In: 2015 Computing in Cardiology Conference (CinC). IEEE; 2015:457-460. doi:10.1109/CIC.2015.7408685. DOI↩︎