Sildenafil-nitric oxide donor combination promotes ventricular tachyarrhythmias in the swine right ventricle.

We tested the hypothesis that sildenafil, singly or in combination with nitric oxide (NO) donors, promotes ventricular tachycardia (VT) and ventricular fibrillation (VF). Vulnerability to VT/VF was tested by rapid pacing in eight isolated normal swine right ventricles (RV). The endocardial activation was optically mapped, and the dynamic action potential duration (APD) restitution curves were constructed with metal microelectrodes. At baseline, no VT/VF could be induced.Sildenafil Citrate (Viagra) (0.2 microg/ml) or NO donor singly or in combination did not alter VT/VF vulnerability. However, when 2 microg/mlSildenafil Citrate (Viagra) was combined with NO donors, the incidence of VT and VF rose significantly (P < 0.01). VT with a single periodic wavefront was induced in five of eight RVs, and VF with multiple wavefronts was induced in all eight RVs. The sildenafil-NO donor pro-VT/VF combination significantly increased the maximum slope of the APD restitution curve and the amplitude of the APD alternans. The pro-VT/VF effects ofSildenafil Citrate (Viagra) were reversible after drug-free Tyrode solution perfusion. We conclude that aSildenafil Citrate (Viagra) (2 microg/ml) and NO donor combination increases VT/VF vulnerability in the normal RV by a mechanism compatible with the restitution hypothesis

Effects of Sildenafil Citrate (Viagra) on hemodynamic parameters during exercise testing and occurrence of ventricular arrhythmias in patients with Erectile Dysfunction and cardiovascular disease.

BACKGROUND: Erectile Dysfunction (ED) is frequently observed in male cardiovascular disease (CVD) patients, creating concern about cardiac risk of their sexual activity, and their therapeutic use of sildenafil. Relatively little information exists aboutSildenafil Citrate (Viagra) effects on exercise testing, hemodynamic parameters or on occurrence of ventricular arrhythmias during normal activities in CVD patients. HYPOTHESIS: Single, oral doses ofSildenafil Citrate (Viagra) do not significantly affect exercise-induced changes in hemodynamic parameters or occurrence of arrhythmias in ED/CVD patients. METHODS: ED patients, with or without CVD, were enrolled in one of two studies. In the first, patients underwent standard (Bruce Protocol) treadmill tests; an initial control test was followed 1 hour later by administration of 100mg oral sildenafil. After another hour, they underwent a second treadmill test. Systolic and diastolic blood pressure (SBP and DBP), heart rate, and double product were determined for each evaluation at pretest, maximum stress, and recovery. In the second, Holter ambulatory ECGs were recorded 5 hours before and 6 hours after 100mg oralSildenafil Citrate (Viagra) administration. RESULTS:Sildenafil Citrate (Viagra) had no clinically significant effects on exercise-induced changes in hemodynamic parameters in cardiac patients and only slight, clinically insignificant effects in noncardiac patients. ECG showedSildenafil Citrate (Viagra) did not affect incidence of ventricular arrhythmias. CONCLUSIONS:Sildenafil Citrate (Viagra) does not alter hemodynamic response to exercise or change incidence of ventricular arrhythmias in men with CVD and ED. These results suggest that, when used in accordance with prescribing information and current treatment guidelines,Sildenafil Citrate (Viagra) should be safe for most patients with both these conditions

Effect of PDE5 inhibition on coronary hemodynamics in pacing-induced heart failure.

Inhibition of phosphodiesterase type 5 (PDE5) can relax systemic and coronary vessels by causing accumulation of cGMP. Both the endothelial dysfunction with decreased nitric oxide production and increased natriuretic peptide levels in congestive heart failure (CHF) have the potential to alter cGMP production, thereby influencing the response to PDE5 inhibition. Consequently, this study examined the effects of PDE5 inhibition withSildenafil Citrate (Viagra) in dogs with CHF produced by rapid ventricular pacing. CHF resulted in decreases of left ventricular (LV) systolic pressure, coronary blood flow, and the maximal first time derivative of LV pressure (LV dP/dt(max)) at rest and during treadmill exercise compared with normal, whereas resting LV end-diastolic pressure increased from 10 +/- 1.4 to 23 +/- 1.4 mmHg.Sildenafil Citrate (Viagra) (2 and 10 mg/kg per os) caused a 5- to 6-mmHg decrease of aortic pressure (P < 0.05), with no change of heart rate, LV systolic pressure, or LV dP/dt(max).Sildenafil Citrate (Viagra) caused no change in coronary flow or myocardial oxygen consumption in animals with CHF at rest or during exercise. In contrast to findings in normal animals,Sildenafil Citrate (Viagra) did not augment endothelium-dependent coronary vasodilation in response to acetylcholine in animals with CHF. Furthermore, Western blotting showed decreased PDE5 protein expression in myocardium from failing hearts. These findings demonstrate that PDE5 contributes little to regulation of coronary hemodynamics in CHF

Sildenafil.

Case reports have documented the utility ofSildenafil Citrate (Viagra) for sexual dysfunction caused by selective serotonin-reuptake inhibitors (SSRIs) and have suggested its potential utility for women and men with various iatrogenic sexual dysfunctions. This brief review summarizes the psychopharmacology of sildenafil, discusses possible interactions with SSRIs, reviews side effects and risks, highlights the need for concomitant psychological counseling, reviews sildenafil's possible mechanisms of action for iatrogenic sexual dysfunctions, and suggests areas for future research

Sildenafil induces retinal vasodilatation in healthy subjects.

BACKGROUND: The cardiovascular effects of Sildenafil Citrate (Viagra), a selective inhibitor of phosphodiesterase type 5 (PDE5), have been extensively studied. However, its effect on human retinal arteries and veins has not yet been investigated. The effect of a single dose administration ofSildenafil Citrate (Viagra) on the retinal vessel diameters of healthy subjects was evaluated. METHODS:Sildenafil Citrate (Viagra) 50 mg was administered to 10 healthy subjects (male:female = 4:6; mean age 31 (SD 6) years). The diameters of retinal arteries and veins were measured by means of a retinal vessel analyser (RVA) immediately before and at 30, 60, 90, and 120 minutes afterSildenafil Citrate (Viagra) uptake. Blood pressure, heart rate, and intraocular pressure were monitored in parallel. RESULTS: A significant increase of 5.8% (p<0.001) in both retinal arterial and venous diameters was found 30 minutes afterSildenafil Citrate (Viagra) uptake. The diameters returned to baseline after 120 minutes. A mild systemic hypotensive response was seen. Changes in heart rate and intraocular pressure were not observed. CONCLUSION:Sildenafil Citrate (Viagra) causes a significant dilatation of retinal arteries and veins in healthy subjects. A possible role for PDE5 in the regulation of retinal blood flow is implicated

Comparison of trimetazidine plusSildenafil Citrate (Viagra) to chronic nitrates in the control of myocardial ischemia during sexual activity in patients with coronary artery disease.

A large proportion of patients who have Erectile Dysfunction also have coronary artery disease (CAD). In these patients, nitrate therapy is a contraindication to the use of sildenafil. To assess whether the metabolic anti-ischemic agent, trimetazidine, is effective in controlling episodes of myocardial ischemia during sexual activity in patients who have CAD and use long-term nitrate therapy, we studied 38 men (57 +/- 6 years of age) who had proved CAD. Patients underwent 24-hour ambulatory electrocardiographic monitoring at baseline, after 1 week of oral nitrate therapy (20 mg 3 times a day), and after 1 week of trimetazidine (20 mg 3 times a day). Patients were asked to engage in >/=1 session of sexual intercourse during each session of ambulatory electrocardiographic monitoring. They were instructed to takeSildenafil Citrate (Viagra) (100 mg) 1 hour before sexual intercourse performed at baseline and during therapy with trimetazidine andSildenafil Citrate (Viagra) or placebo (blinded) during therapy with nitrates. A decrease in total ischemic burden was observed with nitrates and trimetazidine compared with baseline (-3 +/- 1.2 episodes/patient/24 hours vs -5 +/- 1.3 episodes/patient/24 hours and -6 +/- 5 min/patient/24 hours vs -8 +/- 3 min/patient/24 hours, p <0.01 for nitrates and trimetazidine vs baseline). Trimetazidine plusSildenafil Citrate (Viagra) was more effective in controlling episodes of myocardial ischemia during sexual activity than nitrates alone (-45 +/- 11% vs -18 +/- 7%, p <0.04). In conclusion, in patients who have CAD, combination therapy withSildenafil Citrate (Viagra) and trimetazidine is more effective than nitrate therapy in the control of ischemic episodes during sexual activity, suggesting that long-term nitrate therapy may be safely switched to trimetazidine therapy when therapy for Erectile Dysfunction is required

A conscious-rabbit model to study vardenafil hydrochloride and other agents that influence penile erection.

Experimental models to study the effect of agents on penile erection usually include electrical stimulation of peripheral nerves in anesthetized animals combined with systemic or intracavernous injection of drugs. The objective of this study was to demonstrate that conscious rabbits can be used as a simple and quantitative model for the assessment of compounds that show potential for the treatment of Erectile Dysfunction. erection was assessed by measuring the length of uncovered penile mucosa before and after the intravenous (i.v.) administration of agents. Animals did not require anesthesia during the course of the study. The phosphodiesterase 5 (PDE5) inhibitors vardenafil x HCl (hereafter called vardenafil) andSildenafil Citrate (Viagra) were given intravenously, and measurements were taken for 0-5 h. The effects of phentolamine and milrinone were also evaluated. Vardenafil (0.1-3 mg/kg) induced dose-dependent penile erections in conscious rabbits following i.v. administration. The efficacy of vardenafil was potentiated, and the minimal effective dose was reduced significantly to 0.01 mg/kg by simultaneous administration of the nitric oxide (NO) donor sodium nitroprusside (SNP). Administration of the NO-synthase inhibitor L-NAME abolished the effect.Sildenafil Citrate (Viagra) was effective in this model after i.v. administration. The alpha-adrenergic receptor antagonist phentolamine (0.1, 0.3 and 1 mg/kg i.v.) induced erections with a slower t(max) compared with vardenafil and sildenafil. Intravenous administration of the PDE3 inhibitor milrinone (1 mg/kg i.v.) was less effective than the PDE5 inhibitor vardenafil. The conscious rabbit is a suitable and reliable model for the evaluation of compounds with potential for the treatment of Erectile Dysfunction. This was demonstrated using compounds that target different signaling pathways that induce smooth muscle relaxation in the penis

Effect of Sildenafil Citrate (Viagra) on penile erection of rhesus macaques.

AIM: To examine the effect of Sildenafil Citrate (Viagra) on penile erection of male rhesus macaque. METHODS: Twenty Macaca mulatta were divided into theSildenafil Citrate (Viagra) treated and the control groups of 10 animals each. The penile size, the corpus cavernosal electromyogram (EMG) and the intra-corpus cavernosal pressure (ICP) were determined. RESULTS: The diameter of penis and the ICP were significantly increased and the corpus cavernosal EMG significantly reduced in theSildenafil Citrate (Viagra) group. CONCLUSION: Sildenafil Citrate (Viagra) increases the penile size and ICP and reduces the corpus cavernosal EMG in male rhesus macaque