**2. PDE-5 Inhibitors preserve myocardial function following infarction**

A number of pioneering investigations from our laboratory have demonstrated that PDE-5 inhibitors attenuate ischemic injury in animal and cell models (Ockaili et al., 2002; Salloum et al., 2003). In animal models, sildenafil and vardenafil exerted an infarct-sparing effect when given before ischemia (Ockaili et al., 2002; Salloum et al., 2003; Salloum et al., 2006) or at the time of reperfusion (Salloum et al., 2007). Furthermore, chronic treatment with sildenafil immediately after permanent occlusion of the left descending coronary artery (LAD) in mice attenuated ischemic cardiomyopathy (Salloum et al., 2008a). These cardioprotective effects are mediated by activation of protein kinase G (PKG), increased expression of endothelial and inducible nitric oxide synthase (eNOS & iNOS), and augmented Bcl-2/Bax ratio. Due to their powerful anti-ischemic effects, PDE-5 inhibitors became promising candidates for the preservation of cardiac function following AMI. In fact, several studies demonstrated that PDE-5 inhibition preserved left ventricular (LV) function in failing hearts as discussed in the following sections.
