Project Details
Abstract
Acute myocardial infarction (AMI) continues to be the most important cause of morbidity and
mortality despite the recent advances made in its diagnosis and treatment recent years. As a result
of MI, remodeling takes place in the myocardium. Remodeling includes the thinning and the enlargement
of the necrotic tissue, hypertrophy of the intact myocardial tissue for compensation,
and the dilatation of the chamber as a result. Remodeling of ion-channel and transport processes
cause important changes in cellular electrical activity. One of these changes in post-MI heart failure
is the prolongation of the ventricular action potential due to a reduction of transient outward
current Ito density, which underlies the propensity to arrhythmias. In addition, changes in Ca2+
handling contribute importantly to arrhythmogenesis postinfarction. Accordingly, it is of critical
importance to develop therapeutic strategies that will effectively inhibit the development of electrical
remodeling after MI.
The lipid-lowering HMG-CoA reductase inhibitor, satins, reduced morbidity and mortality in
patients with and without coronary disease and have potential benefit to patients with HF. However,
the potential differences between each member of the statin family necessitate careful and systemic
studies. Rosuvastatin is a new highly effective synthetic hydrophilic statin. Several reports have
documented vascular and cardioprotective actions of rosuvastatin. However, the influence of
rosuvastatrin on the electrical remodeling and calcium handling in post-MI heart failure is
unknown. Curcumin is a natural polyphenolic compound. Numerous reports have indicated
that curcumin possesses cardiovascular protective benefits. Recent studies have shown that
curcumin can reduce cardiac hypertrophy. However, the effects of curcumin on cardiac
electrical remodeling following MI-induced hart failure have never been addressed.
In this project, we intend to examine the chronic treatment with either rosuvastatin or
curcumin or other potential cardioprotective drugs on the electrical remodeling and calcium
handling and to verify the possible mechanisms in the coronary artery ligation-induced MI/heart
failure model. After 5 weeks flollow-up, the influences of treatment on the hemodynamic
parameters will be evaluated with PV catheter system. The electrophysiological properties of
conduction system as well as atrial and ventricular arrhythmia vulnerability will be determined in
isolated hearts. The effects on action potential will be determined in atrial and ventricular tissues.
Besides, the ionic currents and intracellular Ca2+ transient will be measured by patch-clamping and
fluorescent imaging techniques, respectively. The effects of drug treatment on structural
remodeling and the expression of Ca2+ handling and ionic channel mRNA and proteins will also be
determined. We hope that this project can provide the important informations about the preventive
effects of rosuvastatin, curcumin or other cardioprotective drugs on the electrical remodeling and
calcium handling of post infarction heart failure.
Project IDs
Project ID:PC10101-1447
External Project ID:NSC99-2320-B182-005-MY3
External Project ID:NSC99-2320-B182-005-MY3
Status | Finished |
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Effective start/end date | 01/08/12 → 31/07/13 |
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