📒 Jones 2015
Quantification of the effects of electrical remodeling due to hypertrophic cardiomyopathy on human ventricular electromechanical activity and energetics1
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)
- 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
- 14% reduction of the PCr/ATP ratio
- 26% decrease in mitochondrial NADPH
The effects increased Ca2+ sensitivity and electrical remodeling have on the contractile properties of the cell, energetics, and levels of ROS production