Cardiac Fibrillation: Mechanisms and Therapy

  • Chen, Peng-Sheng (PI)
  • Zhilin, Qu (PI)
  • John, Scott (PI)
  • Garfinkel, Alan (PI)
  • Olcese, Riccardo (PI)
  • Weiss, James (PI)

Project: Research project

Description

DESCRIPTION (provided by applicant): Ventricular fibrillation (VF) is the most common cause of sudden death, accounting for over 300,000 deaths annually in the US alone. The objective of this proposed Program Project is to develop a rational approach to the therapy of sudden cardiac death (SCO) through understanding the pathogenesis of VF at the mechanistic level. The proposal represents a continuation of our efforts, which began with our SCOR in Sudden Cardiac Death in 1995, to address this objective by combining mathematical biology with experimental biology to integrate information at the molecular, cellular, tissue and systems levels. The theme of this proposed Program Project is that dynamic wave instability (regulated by electrical restitution, intracellular Cai cycling, cardiac memory and diffusive currents) interacts synergistically with increased electrical and structural tissue heterogeneity in the diseased heart to increase the risk of VF and SCO, and that by developing molecular interventions designed to decrease dynamic wave instability, VF and SCO can be prevented. The four projects and three cores will address this theme using experimental approaches including patch clamping, optical mapping with fluorescent dyes, molecular biology, adenoviral gene transfer, and theoretical approaches including mathematical modeling, computer simulations and nonlinear dynamics. Studies ranging from isolated myocytes to intact normal and diseased ventricles, both in vivo and in silico, will be conducted interactively through this Program Project to evaluate comprehensively dynamic factors controlling wave stability as therapeutic targets for prevention of VF and SCO.
StatusFinished
Effective start/end date1/1/055/31/16

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Ventricular Fibrillation
Cardiac Arrhythmias
Heart Diseases
Rabbits
Action Potentials
Calcium
Sudden Cardiac Death
Sarcoplasmic Reticulum
Cardiomyopathies
Maintenance
Research Personnel
Apamin
Membranes
Papillary Muscles

ASJC

  • Medicine(all)