Background: Sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, has endothelium protective
and angiogenic effects.
Objectives: To test if sildenafil improves tissue perfusion and neovascularization and downregulates proinflammatory
molecules following limb ischemia.
Methods: 30 ApoE-/- male mice, bred with cholesterol rich diet for 4 weeks, were anesthetized and underwent
unilateral hind-limb ischemia with ligation of the left femoral artery. Mice were randomized in 2
groups: sildenafil (1 mg/Kg for 7 days intraperitoneally, i.p.) or normal saline (0.4 ml for 7 days, i.p.).
Bilateral hind-limb perfusion was estimated by laser Doppler imaging after surgery on days 0, 7 and 28.
Results: Sildenafil significantly reduced at day 28 compared with day 0 levels of soluble intracellular
adhesion molecule-1(sICAM-1) [2.24(1.81-2.41) vs. 1.29(0.87-1.45) ng/ml, p=0,01], soluble E-selectin
(sE-Selectin) [5.52 (3.67-6.14) vs 1.71 (1.42-2.86) ng/ml, p=0.02] and tissue plasminogen activator inhibitor-
1 (tPAI-1) [0.13(0.07-0.21) vs 0.08 (0.04-0.10) ng/ml, p=0.01] while normal saline had no effect
on the levels of sICAM-1, sE-Selectin and tPAI-1. Treatment with sildenafil was associated with increased
perfusion in the ischemic limb compared with controls.
Conclusion: Sildenafil exerts significant beneficial effects on tissue perfusion and inflammatory status
after limb ischemia, a finding implying neovascularization and potential vascular protective properties of