Effects of (-)-Epicatechin on Myocardial Infarct Size and Left Ventricular Remodeling After Permanent Coronary Occlusion

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:55

Article

Yamazaki, Katrina Go^1,2  Taub, Pam R.^1,2  Barraza-Hidalgo, Maraliz^1,2  Rivas, Maria M.^1,2  Zambon, Alexander C.^1,2  Ceballos, Guillermo³  Villarreal, Francisco J.^1,2 

[1] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

[3] Inst Politecn Nacl, Secc Posgrad, Escuela Super Med, Mexico City, DF, Mexico

关键词: cardioprotection;    catechins;    flavanols;    infarction;    ischemia;   

DOI  :  10.1016/j.jacc.2010.01.055

来源: Elsevier

【 摘 要 】

Objectives We examined the effects of the flavanol (-)-epicatechin on short-and long-term infarct size and left ventricular (LV) structure and function after permanent coronary occlusion (PCO) and the potential involvement of the protective protein kinase B (AKT)/extracellular signal-related kinase (ERK) signaling pathways. Background (-)-epicatechin reduces blood pressure in hypertensive patients and limits infarct size in animal models of myocardial ischemia-reperfusion injury. However, nothing is known about its effects on infarction after PCO. Methods (-)-epicatechin (1 mg/kg daily) treatment was administered via oral gavage to 250 g male rats for 10 days before PCO and was continued afterward. The PCO controls received water. Sham animals underwent thoracotomy and treatment in the absence of PCO. Immunoblots assessed AKT/ERK involvement 2 h after PCO. The LV morphometric features and function were measured 48 h and 3 weeks after PCO. Results In the 48-h group, treatment reduced infarct size by 52%. There were no differences in hemodynamics among the different groups (heart rate and aortic and LV pressures). Western blots revealed no differences in AKT or ERK phosphorylation levels. At 3 weeks, PCO control animals demonstrated significant increases in LV end-diastolic pressure, heart and body weight, and LV chamber diameter versus sham. The PCO plus (-)-epicatechin group values were comparable with those of the sham plus (-)-epicatechin group. Treatment resulted in a 33% decrease in myocardial infarction size. The LV pressure-volume curves demonstrated a right shift in control PCO animals, whereas the (-)-epicatechin curves were comparable with those of the sham group. The LV scar area strains were significantly improved with (-)-epicatechin. Conclusions These results demonstrate the unique capacity of (-)-epicatechin to confer cardioprotection in the setting of a severe form of myocardial ischemic injury. Protection is sustained over time and preserves LV structure and function. The cardioprotective mechanism(s) of (-)-epicatechin seem to be unrelated to AKT or ERK activation. (-)-epicatechin warrants further investigation as a cardioprotectant. (J Am Coll Cardiol 2010; 55: 2869-76) (C) 2010 by the American College of Cardiology Foundation

【 授权许可】

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