Effect of PARP inhibition on in vivo infarct size.
LAD was occluded in female Sprague Dawley (SD) rats for 45 min, followed by 2 hr, reperfusion, n = 7/group. SD hearts show infarct size of 33% of ischemic LV tissue, which is reduced to 18% with the PARP inhibitor, 3-aminobenzamide, (10 mg/kg i.v.) and 22% with the PARP inhibitor, 4-aminobenzamide, (10 mg/kg i.v.) when administered just prior to reperfusion. Administration of the novel PARP inhibitor, GPI 6150, (4 mg/kg i.p., Guilford Pharmaceuticals) 2 hr before ischemia reduces infarct size to 16% of ischemic LV tissue. Infarct size in PARP-1−/− mice subjected to global myocardial I/R is decreased by 35% relative to untreated WT mice. WT, wild type; LV, left ventricle; PARP, polyADPribose polymerase; I/R, ischemia-reperfusion; PARP-1−/−, PolyADPribose polymerase-1 knockout.