1 / 8

Lulu Chu & Chenhong Zhu 08 - 02- 12 CHSL

CCB Final Project Proposal : Investigating the Roles of SERCA and NCX in Heart Failure Using Minimal Models of Ca 2+ Oscillation and Traveling Wave. Lulu Chu & Chenhong Zhu 08 - 02- 12 CHSL. Rationale: Nonlinear Functional Changes in Aortic Banding Heart Failure Animal Model.

aziza
Download Presentation

Lulu Chu & Chenhong Zhu 08 - 02- 12 CHSL

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. CCB Final Project Proposal: Investigating the Roles of SERCA and NCX in Heart Failure Using Minimal Models of Ca2+ Oscillation and Traveling Wave Lulu Chu & Chenhong Zhu 08-02-12 CHSL

  2. Rationale: Nonlinear Functional Changes in Aortic Banding Heart Failure Animal Model

  3. Project Objective 1 and Method • Objective: To understand how functional changes in SERCA or NCX influence the Caioscillation and the transient amplitude/frequency in a compartmental model using parametric studies and bifurcation analysis based on experimental data • Method: • Identify a good minimal ODE model for Ca dynamics including targets of interest and simulate in XPP • Include realistic buffering effect in cytosol and SR (Greenstein & Winslow 2006) • Replace PMCA with NCX formulation from Luo&Rudy 1994 or Weber et al. 2001 • Parametric studies of SERCA, NCX, and determine which has a more profound impact on Ca oscillation amplitude and frequency in heart failure conditions

  4. Preliminary Results: Calcium Dynamics Cytosol LCC RyR Model replication SR Leak PMCA/NCX SERCA

  5. Preliminary Results normal CaivsvSERCA Reduced SERCA normal Increased Extrusion CaivsvPMCA Normal normal

  6. Project Objective 2 and Method • Objective: Better understand Cai traveling wave in 1D spacewith the fire-diffuse-fire model and investigate how SERCA or NCX or RyR changes results in wave propagation failure. • Method: • Derive a new 1D PDE for Cai which includes the buffering effect in cytosol based on rapid buffer approximation (RBA) and fluxes of interests • Implement the model using finite difference scheme in XPP or Matlab to do numerical integrations with new parameters set from the first objective • Parametric studies of SERCA and NCX functions and investigate how they change normal behavior of Cai wave speed and propagation

  7. Model Plan for 1D Ca Traveling Model • RBA • Treat all the fluxes as point sources • Use finite difference method

  8. Anticipated Difficulties • XPP numerics issue • Implementation with 1D PDE model and position of Ca reaction (influx/efflux)

More Related