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PRE-CLINICAL RESEARCH

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

Katrina Go Yamazaki, PhD^_*, Pam R. Taub, MD^_*, Maraliz Barraza-Hidalgo, BS^_*, Maria M. Rivas, BS^_*, Alexander C. Zambon, PhD^_*, Guillermo Ceballos, MD, PhD and Francisco J. Villarreal, MD, PhD^_*,_*

^_* Departments of Medicine and Pharmacology, University of California, San Diego, La Jolla, California
Escuela Superior de Medicina del Instituto Politécnico Nacional, Seccion de Posgrado, Mexico City, Mexico

Manuscript received September 1, 2009; revised manuscript received January 7, 2010, accepted January 12, 2010.

^_* Reprints requests and correspondence: Dr. Francisco Villarreal, Department of Cardiology, University of California, San Diego, 9500 Gilman Drive, 0613J, BSB 4028, La Jolla, California 92093 (Email: fvillarr{at}ucsd.edu).

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.

Key Words: cardioprotection • catechins • flavanols • infarction • ischemia

Abbreviations and Acronyms   AKT = protein kinase B   CVD = cardiovascular disease   ERK = extracellular signal-related kinase   IR = ischemia–reperfusion   LV = left ventricle/ventricular   MI = myocardial infarction   PCO = permanent coronary occlusion   RISK = reperfusion injury salvage kinase

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