ELECTROPHYSIOLOGY AFTER MYOCARDIAL INFARCTION

Project: Research project

Project Details

Description

DESCRIPTION: Life-threatening arrhythmias have complex and multifactorial
pathophysiologies, among which are structural predisposing influences, acute
risk factors that trigger fatal arrhythmias, and individual susceptibility
based on genetic determinants. The specific aims of this proposal are to
use an experimental model of healed myocardial infarction (HMI) in cats to
provide understanding of: (1) the mechanisms by which chronic ischemic
heart disease predisposes to life-threatening arrhythmias; (2) the
electrophysiology of transient triggering factors; and (3) individual animal
susceptibility to arrhythmic responses. Three hypotheses will be tested:
(1) regional hypertrophy in hearts with HMI regulates electrophysiology by
altering regional ion channel function in ways similar to changes caused by
global hypertrophy; (2) local changes in ion channel function in areas of
regional hypertrophy cause susceptibility to the generation of
afterdepolarizations and triggered activity, and predispose to reentry by
dispersion of refractoriness; and (3) paired studies of ion channel currents
in myocytes and T-lymphocytes will demonstrate homologous characteristics
and responses to interventions. The latter will allow the use of the
T-lymphocyte as a surrogate for myocytes for screening individual animals
for responses to acute triggers. Conventional patch-clamp techniques will
be used to study four membrane currents (ICa,L, IK, Ito, I K-ATP) in
myocytes and IK -like and Ito -like currents in T-lymphocytes. After
determining baseline regional characteristics in HMI, including epicardial
and endocardial differences, the effect of transient triggering influences,
such as ischemia/reperfusion and proarrhythmic substances on ion channels
will be determined. In parallel, the comparative responses of paired
myocytes and lymphocytes from the same animals will be established. The
goals of this work are to define the mechanisms by which regional
hypertrophy in HMI contributes to electrophysiologic heterogeneity and the
potential for generating arrhythmias, and the development of a method for
screening specific individual animal responses to arrhythmogenic triggering
factors using circulating T-lymphocytes.
StatusFinished
Effective start/end date12/31/895/31/02

Funding

  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.