Phosphodiesterase-5 (PDE-5) inhibitors sildenafil (SIL) and vardenafil (VAR) induce powerful cardioprotection against ischemia/reperfusion injury (I/R) in male animal models. Since the impact of PDE-5 inhibitors on the female cardiovascular system following ischemia remains unknown, we interrogated the effect of SIL and VAR on I/R in female mice. Methods: Adult female mice were pretreated (ip, bid) with SIL (0.71 mg/kg), VAR (0.14 mg/kg) or saline one hr before left coronary artery ligation for

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... 30 min and reperfusion for 24 hr. At the end of reperfusion, infarct size (IS) was measured using TTC staining and apoptosis was measured using TUNEL assay. Left ventricular (LV) function was evaluated using echocardiography. Results: Myocardial IS (mean ± SE) was reduced with SIL (9.1 ± 1.0%) and VAR (8.8±1.1%) as compared to saline (39.9±4.5%, P<0.05). The apoptotic index was 9.0 ± 3.3% for saline, 1.9 + 0.9% and 2.4 ± 0.9% for SIL and VAR, respectively. LV end-diastolic and end-systolic diameters increased 7 days post MI with saline. In contrast, no dilatation was detected in SIL and VAR groups. Moreover, fractional shortening (FS) decreased 7 days post MI with saline, but was well preserved with SIL and VAR (Table) . Furhtermore, survival rate was lower with saline (57%) as compared to SIL (95%) and VAR (100%). Conclusions: PDE-5 inhibitors induce powerful cardioprotection in female mice. We propose that PDE-5 inhibition may be a novel therapeutic strategy against I/R in women with coronary artery disease.