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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.

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Lulu Chu & Chenhong Zhu 08 - 02- 12 CHSL

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  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)

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