Abstract
The aim of this study was to determine, in an animal model, the effects of tadalafil on myocardial infarct size (IS), hemodynamics and regional myocardial blood flow after myocardial ischemia and reperfusion. Patients with erectile dysfunction (ED) often have risk factors for coronary artery disease. Tadalafil, a long-acting inhibitor of the enzyme phosphodiesterase-5 (PDE5), is used for the treatment of ED; there are no previous data regarding tadalafil in the setting of coronary artery occlusion (CAO). Sprague–Dawley male rats were treated with tadalafil or vehicle (10 mg/kg, by gastric gavage), 2 h before a 30 min CAO. Heart rate was comparable between tadalafil and control groups. Tadalafil reduced mean arterial pressure (P=0.009), systolic (P=0.035) and diastolic (P=0.009) blood pressures during ischemia/reperfusion. Tadalafil significantly reduced IS (42±2%) versus controls (54±3%) (P=0.006). For the first time, we showed that the PDE5 inhibitor, tadalafil, was well tolerated and cardioprotective in the setting of an experimental myocardial infarction, by substantially reducing ischemic cell death.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 8 print issues and online access
$259.00 per year
only $32.38 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB . Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 1994; 151: 54–61.
Laumann EO, Paik A, Rosen RC . Sexual dysfunction in United States: prevalence and predictors. JAMA 1999; 281: 537–544.
Blumentals WA, Gomez-Caminero A, Joo S, Vannappaggari V . Should erectile dysfunction be considered as a marker for acute myocardial infarction? Results from a retrospective cohort study. Int J Impot Res 2004; 16: 350–353.
Kaiser DR, Billups K, Mason C, Wetterling R, Lundberg JL, Bank AJ . Impaired brachial artery endothelium-dependent and -independent vasodilation in men with erectile dysfunction and no other clinical cardiovascular disease. J Am Coll Cardiol 2004; 43: 179–184.
Kloner RA, Jarow JP . Erectile dysfunction and sildenafil citrate and cardiologists. Am J Cardiol 1999; 83: 576–582.
Aversa A, Pili M, Fabbri A, Spera E, Spera G . Erectile dysfunction: expectations beyond phosphodiesterase type-5 inhibition. J Endocrinol Invest 2004; 27: 192–206.
Kloner RA . Cardiovascular effects of the 3 phosphodiesterase-5 inhibitors approved for the treatment of erectile dysfunction. Circulation 2004; 110: 3149–3155.
Jackson G, Kloner RA, Costigan TM, Warner MR, Emmick JT . Update on clinical trials of tadalafil demonstrates no increased risk of cardiovascular adverse effects. J Sex Med 2004; 1: 161–167.
Kloner RA, Padma-Nathan H . Erectile dysfunction in patients with coronary artery disease. Int J Impot Res 2005; 17: 209–215.
Kukrejia RC, Ockaili R, Salloum F, Yin C, Hawkins J, Das A et al. Cardioprotection with phosphodiesterase-5 inhibition – a novel preconditioning strategy. J Mol Cell Cardiol 2003; 36: 165–173.
Rosano GMC, Aversa A, Vitale C, Fabbri A, Fini M, Spera G . Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk. Eur Urol 2005; 47: 214–222.
Takimoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER et al. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med 2005; 11: 214–222.
Ockaili R, Salloum F, Hawkins J, Kukreja RC . Sildenafil (Viagra) induces powerful cardioprotective effect via opening of mitochondrial KATP channels in rabbits. Am J Physiol Heart Circ Physiol 2002; 283: H1263–H1269.
Rosen RC, Kostis JB . Overview of phosphodiesterase 5 inhibition in erectile dysfunction. Am J Cardiol 2003; 92 (Suppl): 9M–18M.
Kloner RA, Mitchell M, Emmick JT . Cardiovascular effects of tadalafil. Am J Cardiol 2003; 92 (Suppl): 37M–46M.
Kloner RA, Mitchell M, Emmick JT . Cardiovascular effects of tadalafil in patients on common antihypertensive therapies. Am J Cardiol 2003; 92 (Suppl): 47M–57M.
American Heart Association. Position of the American Heart Association on research animal use. Circulation 1985; 71: 849A–850A.
Heymann MA, Payne BD, Hoffman JE, Rudolph AM . Blood flow measurement with radionuclide-labeled particles. Prog Cardiovasc Dis 1977; 20: 55–79.
Bischoff E . Potency, selectivity, and consequences of nonselectivity of PDE inhibition. Int J Impot Res 2004; 16 (Supp 1): S11–S14.
Carson CC, Rajfer J, Eardley I, Carrier S, Dennes JS, Walker DJ et al. The efficacy and safety of tadalafil: an update. BJU Int 2004; 39: 1276–1281.
Montorsi F, Padma Nathan H, McCullough A, Brock GB, Broderick G, Ahuja S et al. Tadalafil in the treatment of erectile dysfunction following bilateral nerve-sparing radical retropubic prostatectomy: a randomized, double-blind, placebo-controlled trial. J Urol 2004; 172: 1036–1041.
Sastry BK, Narasimhan C, Reddy NK, Raju BS . Clinical efficacy of sildenafil in primary pulmonary hypertension: a randomized, placebo-controlled, double-blind, crossover study. J Am Coll Cardiol 2004; 43: 1149–1153.
Tantini B, Manes A, Fiumana E, Pignatti C, Guarnieri C, Zannoli R et al. Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle cells. Basic Res Cardiol 2005; 100: 131–138.
Katz SD, Balidemaj K, Homma S, Wu H, Wang J, Maybaum S . Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure. J Am Coll Cardiol 2000; 36: 845–851.
Desouza C, Parulkar A, Lumpkin D, Akers D, Fonseca VA . Acute and prolonged effects of sildenafil on brachial artery flow-mediated dilatation in type-2 diabetes. Diabetes Care 2002; 25: 1336–1339.
Kimura M, Higashi Y, Hara K, Noma K, Sasaki S, Nakagawa K et al. PDE5 inhibitor sildenafil citrate augments endothelium-dependent vasodilation in smokers. Hypertension 2003; 41: 1106–1110.
Reffelmann T, Kloner RA . Effects of sildenafil on myocardial infarct size, microvascular function, and acute ischemic left ventricular dilation. Cardiovasc Res 2003; 59: 441–449.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sesti, C., Florio, V., Johnson, E. et al. The phosphodiesterase-5 inhibitor tadalafil reduces myocardial infarct size. Int J Impot Res 19, 55–61 (2007). https://doi.org/10.1038/sj.ijir.3901497
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.ijir.3901497
Keywords
This article is cited by
-
The potential therapeutic effect of phosphodiesterase 5 inhibitors in the acute ischemic stroke (AIS)
Molecular and Cellular Biochemistry (2023)
-
Effects of phosphodiesterase-5 inhibitor on ischemic kidney injury during nephron sparing surgery: quantitative assessment by NGAL and KIM-1
World Journal of Urology (2015)
-
Effectiveness and Safety of Phosphodiesterase 5 Inhibitors in Patients with Cardiovascular Disease and Hypertension
Current Hypertension Reports (2013)
-
Effects of sildenafil and/or muscle derived stem cells on myocardial infarction
Journal of Translational Medicine (2012)
-
Chronic treatment with long acting phosphodiesterase-5 inhibitor tadalafil alters proteomic changes associated with cytoskeletal rearrangement and redox regulation in Type 2 diabetic hearts
Basic Research in Cardiology (2012)