Effects of Statin, Curcumin and Cardioprotective Agents on Atrial and Ventricular Electrical Remodeling and Calcium Handling in Infracted Rat

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

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:PC9907-2527
External Project ID:NSC99-2320-B182-005-MY3
StatusFinished
Effective start/end date01/08/1031/07/11

Keywords

  • Myocardial infarction
  • Heart failure
  • Electrical remodeling
  • Calcium handling
  • Ionic channels
  • Atorvastatin
  • Curcumin

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