Acute Coronary Syndromes AMPLIFICATION OF THE MYOCARDIAL INFARCT SIZE LIMITING EFFECTS OF EXENATIDE WITH CILOSTAZOL, A PHOSPHODIESTERASE III INHIBITOR

Asrac Caegor: 6. Acue Coroar Sromes: Basicreseaio umer: 1177-583Auhors: Yochai Birnbaum, Alexander C. Castillo, Ling Shukuan, Mandeep Bajaj, Jose R. Perez-Polo, Yumei Ye, University of Texas Medical Branch, Galveston, TX, USA, Baylor Collge of Medicine, Houston, TX, USABackground: Glucago-lie eie (G1) aalogues reuce mocarial ifarc size (IS) i oiaeic aimals. Ischemic a harmacological recoiioig of iaeic aimals is limie. Acivaio of he G1 receors icreases iracellular cAM wih owsream acivaio of roei iase A (KA). Cilosazol (CI), a hoshoieserase III ihiior reves he egraaio of cAM a augmes he IS-limiig effecs of sais. We assesse wheher CI augmes he IS-limiig effecs of exeaie (EX), a G1 aalogue, icreasig iracellular cAM i mice wih e-2 iaees mellius. Methods: D/D mice fe a Weser Die receive oral CI (10 mg/g) or vehicle oral gavage 24h efore surger. Oe hour efore surger mice receive S.C. EX (1 mcg/g) or vehicle. Aiioal mice receive H89, a KA ihiior, aloe or wih CI+EX. Mice were sujece o 30 mi coroar arer occlusio a 24h reerfusio. Ischemic area a ris (AR) was assesse lue e a IS TTC. Results: Bo weigh, lef vericular weigh a he size of he AR were comarale amog grous. Boh EX a CI reuce IS. IS was he smalles i he CI+EX grou (Figure). IS i he H89 grou was 48.2±4.6% of he AR a i he CI+EX+H89 45.8±1.4% (=.117). Boh EX a CI icrease cAM. cAM levels were sigiical higher i he CI+EX grou. Conclusion: EX a CI have aiive IS-limiig effecs i iaeic mice. The aiive effecs are relae o cAM iuce KA acivaio, as H89 loce he effec of CI+EX.