Short- and long-term effects of (-)-epicatechin on myocardial ischemia-reperfusion injury.
Epidemiological studies have shown a correlation between flavonoid-rich diets and improved cardiovascular prognosis. Cocoa contains large amounts of flavonoids, in particular flavanols (mostly catechins and epicatechins). Flavonoids possess pleiotropic properties that may confer protective effects to tissues during injury. We examined the ability of epicatechin to reduce short-and long-term ischemia-reperfusion (I/R) myocardial injury. Epicatechin (1 mg.kg(-1).day(-1)) pretreatment (Tx) was administered daily via oral gavage to male rats for 2 or 10 days. Controls received water. Ischemia was induced via a 45-min coronary occlusion. Reperfusion was allowed until 48 h or 3 wk while Tx continued. We measured infarct (MI) size (%), hemodynamics, myeloperoxidase activity, tissue oxidative stress, and matrix metalloproteinase-9 (MMP-9) activity in 48-h groups. Cardiac morphometry was also evaluated in 3-wk groups. With 2 days of Tx, no reductions in MI size occurred. After 10 days, a significant approximately 50% reduction in MI size occurred. Epicatechin rats demonstrated no significant changes in hemodynamics. Tissue oxidative stress was reduced significantly in the epicatechin group vs. controls. MMP-9 activity demonstrated limited increases in the infarct region with epicatechin. By 3 wk, a significant 32% reduction in infarct size was observed with Tx, accompanied with sustained hemodynamics and preserved chamber morphometry. In conclusion, epicatechin Tx confers cardioprotection in the setting of I/R injury. The effects are independent of changes in hemodynamics, are sustained over time, and are accompanied by reduced levels of indicators of tissue injury. Results warrant the evaluation of cocoa flavanols as possible therapeutic agents to limit ischemic injury.
Department of Medicine, UCSD Cardiology, 9500 Gilman Dr. 0613J, BSB 4028, La Jolla, CA 92093, USA.
Katrina Go
KG
Yamazaki
Diego
D
Romero-Perez
Maraliz
M
Barraza-Hidalgo
Michelle
M
Cruz
Maria
M
Rivas
Brenda
B
Cortez-Gomez
Guillermo
G
Ceballos
Francisco
F
Villarreal
D000284:Administration, Oral; D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002392:Catechin / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D002317:Cardiovascular Agents; D002392:Catechin; D009195:Peroxidase; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9