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Chattipakorn N, Fotuhi PC, Sreenan CM, White JB & Ideker RE (2000). Pacing after shocks stronger than the upper limit of vulnerability: impact viagra super active coupon on fibrillation induction. Influence of postshock epicardial activation patterns on initiation of ventricular fibrillation by upper limit of vulnerability shocks. Chattipakorn N, Banville I, Gray RA & Ideker RE (2001). Mechanism of ventricular defibrillation for near-defibrillation threshold shocks: a whole-heart optical mapping study in swine. Chattipakorn N, Fotuhi PC, Chattipakorn SC & Ideker RE (2003). Three-dimensional mapping of earliest activation after near-threshold ventricular defibrillation shocks. Journal of Cardiovascular Electrophysiology , 14: 65-69. Pediatric Clinics of North America , 51: 1211-1221. Pacing following shocks stronger than the defibrillation threshold: impact on defibrillation outcome. Journal of Cardiovascular Electrophysiology , 11: 1022-1028. Prediction of defibrillation outcome by epicardial activation patterns following shocks near the defibrillation threshold. Journal of Cardiovascular Electrophysiology , 11: 1014-1021. Chattipakorn N, Banville I, Gray RA & Ideker RE (2004). Effects of shock strengths on ventricular defibrillation failure. Sildenafil in patients with cardiovascular disease. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Alloggiamento T, Zipp C, Raxwal VK, Ashley E, Dey S, Levine S & Froelicher VF (2001). Padma-Nathan H, Eardley I, Kloner RA, Laties AM & Montorsi F (2002). A 4-year update on the safety of sildenafil citrate (Viagra). McGovern PG, Jacobs Jr DR, Shahar E, Arnett DK, Folsom AR, Blackburn H & Luepker RV (2001). Trends in acute coronary heart disease mortality, morbidity, and medical care from 1985 through 1997: the Minnesota heart survey. Sildenafil: a 4-year update in the treatment of 20 million erectile dysfunction patients. Geelen P, Drolet B, Rail J, Berube J, Daleau P, Rousseau G, Cardinal R, O'Hara GE & Turgeon J (2000). Sildenafil (Viagra) prolongs cardiac repolarization by blocking the rapid component of the delayed rectifier potassium current. Swissa M, Ohara T, Lee MH, Kaul S, Shah PK, Hayashi H, Chen PS & Karagueuzian HS (2002). Sildenafil-nitric oxide donor combination promotes ventricular tachyarrhythmias in the swine right ventricle. Vardi Y, Bulus M, Reisner S, Nassar S, Aboud L, Sprecher E & Gruenwald I (2003). Effects of sildenafil citrate (Viagra) on hemodynamic parameters during exercise testing and occurrence of ventricular arrhythmias in patients with erectile dysfunction and cardiovascular disease. Kaya D, Guler C, Esen AM, Barutcu I & Dincel C (2004). Sildenafil citrate does not alter ventricular repolarization properties: novel evidence from dynamic QT analysis. Annals of Noninvasive Electrocardiology , 9: 228-233. Sildenafil (Viagra) reduces arrhythmia severity during ischaemia 24 h after oral administration in dogs. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Sildenafil induces delayed preconditioning through inducible nitric oxide synthase-dependent pathway in mouse heart. Das S, Maulik N, Das DK, Kadowitz PJ & Bivalacqua TJ (2002). Cardioprotection with sildenafil, a selective inhibitor of cyclic 3',5'-monophosphate-specific phosphodiesterase 5. Drugs under Experimental and Clinical Research , 28: 213-219. Effects of sildenafil on myocardial infarct size, microvascular viagra super active coupon function, and acute ischemic left ventricular dilation. Ockaili R, Salloum F, Hawkins J & Kukreja RC (2002). Sildenafil (Viagra) induces powerful cardioprotective effect via opening of mitochondrial K(ATP) channels in rabbits. The pharmacology of sildenafil, a novel and selective inhibitor of phosphodiesterase (PDE) type 5. Japanese Journal of Pharmacology , 114 (Suppl 1): 22P-26P. Late preconditioning elicited by activation of adenosine A(3) receptor in heart: role of NF-kappa B, iNOS and mitochondrial K(ATP) channel. Journal of Molecular and Cellular Cardiology , generic viagra pills for sale 34: 263-277. The role of mitochondrial KATP channels in cardioprotection. Protein kinase C plays an essential role in sildenafil-induced cardioprotection in rabbits. Chattipakorn, Cardiac Electrophysiology Unit, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. Research supported in part by the Thailand Research Fund (TRF) grant RSA4680010 viagra cheap generic (N. Chattipakorn) and the funding from the China Medical Board, Faculty of Medicine, Chiang Mai University (N. All the contents of this journal, except where otherwise noted, is licensed under a Creative Commons Attribution License. Bandeirantes, 3900 14049-900 Ribeirao Preto SP Brazil Tel. Use of Sildenafil in Patients with Cardiovascular Disease. Armenio Costa Guimaraes, Marcus Vinicius Bolivar Malachias, Otavio Rizzi Coelho, Emilio Cesar Zilli, Rafael Leite Luna. Erectile dysfunction, formerly called impotence, is the inability of the male to achieve or maintain penile erection and thus engage in coitus 1 . It is common among patients with cardiovascular diseases or their risk factors. This dysfunction occurs mainly among individuals with coronary artery disease, after episodes of acute ischemic syndrome, hypertensive patients underpharmacologic treatment, and among patients with heart failure. In approximately 85% of these cases, the fear of a cardiac event during coitus constitutes an important factor for erectile dysfunction 2-4 . Discovery of sildenafil citrate has represented a great development in the treatment of erectile dysfunction; it may benefit, among many others, those patients with cardiovascular diseases or with their risk factors 5 . Even though clinical trials including more than 3,700 patients with erectile dysfunction, 2,000 of them in controlled studies with placebo, have shown a good tolerance for the medication, more intense circulatory side effects may occur in individuals with cardiovascular disease, mainly those patients using medications with organic nitrates 6 . These circumstances require recommendations by specialists so that sildenafil can be viagra super active coupon safely used. In the Massachusetts Male Aging Study (MMAS), erectile dysfunction significantly correlated with 3 groups of diseases: atherosclerosis, hypertension, and diabetes mellitus 7 . The most important organic factor involved in this dysfunction is impairment of penile blood flow, common in men above 50 years of age with atherosclerosis or diabetes. It is estimated that 50% (ranging from 28% to 59%) of diabetic patients have erectile dysfunction. Mechanism of action ? Sildenafil belongs to the class of phosphodiesterase inhibitors. The erectile action of sildenafil combines increase in arterial flow with reduction in the venous flow of cavernous body of penis. Sildenafil leads to relaxation of smooth muscle of penile arteries and trabeculae surrounding the sinusoidal spaces, resulting in a greater engorgement of cavernous body. The trabeculae of engorged sinusoidal spaces compress the penile venules against the tunica albuginea, reducing venous flow, contributing to maintenance of engorgement of cavernous body 8 . Relaxation of this smooth muscle results from a decrease in intracellular calcium mediated by accumulation of the second messenger, the cyclic guanosine monophosphate (cGMP), whose production results from activation of guanyl cyclase by nitric oxide produced by the stimulus of endothelial cells generated by sexual desire. The limiting factor in this process is degradation of cGMP by the enzyme 5 phosphodiesterase (PDE5) present in high concentrations in the penile structures. Sildenafil facilitates erection due to its high specificity and potency as an inhibitor of this phosphodiesterase 9,10 . Acting in the final phase of the biochemical cycle of erection, the action of sildenafil depends on sexual desire and, therefore, it is not an aphrodisiac. Lower concentrations of PDE5 may also be found in the smooth muscle of arteries in general, of viscera and trachea, and in platelets. Seven types of phosphodiesterases have already been identified. Sildenafil has a lower inhibiting power upon other isoenzymes of phosphodiesterase as compared with PDE5. It has a weak selectivity (1,000 times smaller) for PDE2 (predominates in the adrenal cortex), PDE3 (smooth muscle, platelets and myocardium), and PDE4 (lymphocytes of the brain and lungs). It has a moderate selectivity (80 or more times smaller) for PDE1 (predominates in the brain, kidneys and smooth muscle) and an only 10-times smaller selectivity for PDE6 (photoreceptors of the retina), the probable cause of visual disorders that may occur with the use of sildenafil.
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