Exenatide reduces infarct size and improves cardiac function in a porcine model of ischemia and reperfusion injury.
J Am Coll Cardiol
; 53(6): 501-10, 2009 Feb 10.
Article
em En
| MEDLINE
| ID: mdl-19195607
ABSTRACT
OBJECTIVES:
This study sought to examine whether exenatide is capable of reducing myocardial infarct size.BACKGROUND:
Exenatide is a glucagon-like peptide (GLP)-1 analogue with insulinotropic and insulinomimetic properties. Because insulin and GLP-1 have been described as reducing apoptosis, exenatide might confer cardioprotection after acute myocardial infarction (MI).METHODS:
Pigs were randomized to exenatide or phosphate-buffered saline (PBS) treatment after 75 min of coronary artery ligation and subsequent reperfusion. Infarct size was assessed with Evans Blue (Sigma-Aldrich, St. Louis, Missouri) and triphenyltetrazolium chloride. Cardiac function was measured with epicardial ultrasound and conductance catheter-based pressure-volume loops. Western blotting, histology, and activity assays were performed to determine markers of apoptosis/survival and oxidative stress.RESULTS:
Exenatide reduced myocardial infarct size (32.7 +/- 6.4% vs. 53.6 +/- 3.9%; p = 0.031) and prevented deterioration of systolic and diastolic cardiac function (systolic wall thickening 47.3 +/- 6.3% vs. 8.1 +/- 1.9%, p < 0.001; myocardial stiffness 0.12 +/- 0.06 mm Hg/ml vs. 0.22 +/- 0.07 mm Hg/ml; p = 0.004). After exenatide treatment, myocardial phosphorylated Akt and Bcl-2 expression levels were higher compared with those after PBS treatment, and active caspase 3 expression was lower. In addition, fewer cells were terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling-positive. In addition, nuclear oxidative stress as assessed with an 8-hydroxydeoxyguanosine staining was reduced in the exenatide treatment arm, and superoxide dismutase activity and catalase activity were increased. Serum insulin levels increased after exenatide treatment, without affecting glucose levels.CONCLUSIONS:
These data identify exenatide as a potentially effective compound to reduce infarct size in adjunction to reperfusion therapy in patients with acute MI.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Peçonhas
/
Traumatismo por Reperfusão Miocárdica
/
Hipoglicemiantes
/
Infarto do Miocárdio
Limite:
Animals
Idioma:
En
Revista:
J Am Coll Cardiol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Holanda