Effects of (-)-epicatechin on myocardial infarct size and left ventricular remodeling after permanent coronary occlusion.
OBJECTIVE
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.
Yamazaki
Katrina Go
KG
Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA.
Taub
Pam R
PR
Barraza-Hidalgo
Maraliz
M
Rivas
Maria M
MM
Zambon
Alexander C
AC
Ceballos
Guillermo
G
Villarreal
Francisco J
FJ
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D002392:Catechin / Q000494:pharmacology*; D003326:Coronary Circulation; D054059:Coronary Occlusion / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000502:physiology*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D011336:Probability; D011859:Radiography; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D015996:Survival Rate; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
D002392:Catechin