title: Sildenafil citrate (viagra) induces cardioprotective effects after ischemia/reperfusion injury in infant rabbits.
abstract: Infants undergoing surgery for congenital heart disease are at risk for myocardial ischemia during cardiopulmonary bypass, circulatory arrest, or low-flow states. The purpose of this study was to demonstrate the effects of sildenafil, a selective phosphodiesterase-5 (PDE-5) inhibitor on myocardial functional improvement and infarct size reduction during ischemia/reperfusion injury in infant rabbits. Infant rabbits (aged 8 wk) were treated with sildenafil citrate (0.7 mg/kg i.v.) or normal saline 30 min before sustained ischemia for 30 min and reperfusion for 3 h. Transesophageal echocardiography (TEE) was used to assess left ventricular cardiac output (LVCO) and aortic velocity time integral (VTI). After ischemia/reperfusion, risk area was demarcated by Evan's blue dye and infarct size determined by computer morphometry of triphenyltetrazolium chloride-stained sections. The sildenafil-treated group had preservation and elevation in LVCO (143% of baseline, p < 0.05) and an elevated aortic VTI (145% of baseline, p < 0.05) after 30 min of ischemia compared with the control group LVCO (72% of baseline, p < 0.05) and aortic VTI (73% of baseline, p < 0.05). This is a statistically significant increase in LVCO and aortic VTI in the sildenafil group compared with controls (n = 6/group, p < 0.05). The sildenafil-treated group had significant reduction in infarct size (15.5 +/- 1.2 versus 33 +/- 2.3 in the saline group, % risk area, mean +/- SEM, n = 10-15/group, p < 0.05). For the first time, we have shown that sildenafil citrate promotes myocardial protection in infant rabbits as evidenced by postischemic preservation and elevation in LVCO and aortic VTI and reduction in infarct size.
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics, Virginia Commonwealth University Health System, Richmond, VA 23298, USA.
authors.forename: Yvonne A
authors.initials: YA
authors.lastname: Bremer
authors.forename: Fadi
authors.initials: F
authors.lastname: Salloum
authors.forename: Ramzi
authors.initials: R
authors.lastname: Ockaili
authors.forename: Eric
authors.initials: E
authors.lastname: Chou
authors.forename: William B
authors.initials: WB
authors.lastname: Moskowitz
authors.forename: Rakesh C
authors.initials: RC
authors.lastname: Kukreja
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000818:Animals; D001011:Aorta / Q000473:pathology; D002302:Cardiac Output; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004452:Echocardiography / Q000379:methods; D005070:Evans Blue / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000188:drug therapy; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy*; D000068677:Sildenafil Citrate; D013450:Sulfones; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology; D016277:Ventricular Function, Left
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D005070:Evans Blue; D000068677:Sildenafil Citrate; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5