Sildenafil Group Research Articles

Sildenafil selectively inhibits acute pulmonary embolism-induced pulmonary hypertension

Selective pulmonary vasodilators attenuate acute pulmonary embolism (APE)-induced pulmonary hypertension. We examined the effects of intravenous sildenafil on the hemodynamic and respiratory changes caused by APE in anesthetized dogs. Sham operated animals ( n=3) received only saline infusions. APE was induced by intravenous injections of microspheres in amounts adjusted to increase mean pulmonary artery pressures (MPAP) by 20 mmHg. Hemodynamic evaluation was performed and arterial blood samples were drawn for blood gas analysis at baseline, 15 and 30 min after APE was induced, and then 15, 30, and 45 min after the sildenafil infusion (1 mg kg −1 infused intravenously in 15 min followed by 0.3 mg kg −1 h −1 for 30 min) started in the Sildenafil group ( n=7), or saline infusion started in the control group ( n=8). APE induced sustained pulmonary hypertension and 325% increase in pulmonary vascular resistance index (PVRI) without significant changes in the other hemodynamic parameters. While the animals in the control group showed no further changes in MPAP and PVRI, a significant decrease in MPAP and PVRI (−25 and −45%, respectively; P<0.05 both) was observed with sildenafil. No significant changes in the other hemodymamic parameters were observed in both groups. APE decreased PaO 2, whereas sildenafil attenuated the decrease in PaO 2 ( P<0.05). We conclude that intravenous sildenafil can selectively attenuate the increases in MPAP and PVRI after APE.

Sildenafil Citrate (Viagra) Induces Cardioprotective Effects after Ischemia/Reperfusion Injury in Infant Rabbits

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.

173 Effects of Phosphodiesterase 5 Inhibitor on Pulmonary Vascular Reactivity in The Fetal Lamb

Background: Nitric Oxide (NO) released by pulmonary vascular endothelium is a potent vasodilator related to increased cGMP content. Hydrolysis of cGMP is achieved predominantly by cGMP–specific phosphodiesterases (PDEs). Sildenafil (SILD) is a selective phosphodiesterase–5 (PDE–5) inhibitor. The purpose of the study was to assess the effects of sildenafil on pulmonary vascular circulation during the perinatal period.Methods: 12 pregnant ewes were operated on between 128 and 130 days gestation (term = 145 d). Catheters were placed into the ascending aorta, superior vena cava, main pulmonary artery and left atrium. An ultrasonic flow transducer was placed around left pulmonary artery (LPA). An inflatable vascular occluder was placed around ductus arteriosus (DA). Acute DA compression increases pulmonary artery pressure (PAP) causing an increase in pulmonary blood flow (Q) and a progressive decline in pulmonary vascular resistance (PVR). Fetal lambs were divided in two groups: 1) a SILD group infused continuously with SILD at a rate of 24 mg/day (n=6) and; 2/ control group (CONT) infused with saline (n=6). After 24 hrs of infusion, we compared the hemodynamic response of LPA to: 1) increased fetal PaO2 (maternal O2 inhalation for 30 min), and; 2) increase in vascular shear-stress (flow-induced pulmonary vasodilatation related to DA compression).Results: Mean PAP, Q and PVR were similar in both groups before and after 24 h of SILD or saline infusion. Despite similar baseline values, PVR during maternal O2 inhalation was lower in SILD than in CONT group (0.23±0.01 vs 0.27±0.01 mmHg/ml.min−1 respectively) (p<0.01). Furthermore, drop in PVR during acute DA compression was greater in the SILD group (from 0.54±0.03 to 0.26±0.02 mmHg/ml.min−1) than in the CONT group (from 0.55±0.04 to 0.39±0.02 mmHg/ml.min−1) (p<0.01).Conclusion: Although no difference was found in the basal pulmonary vascular tone, sildenafil increases pulmonary vascular reactivity in the ovine fetus. These data suggest that PDE–5 is involved in the regulation of pulmonary vascular reactivity during the perinatal period. We further speculate that specific inhibitor of PDE–5 may potentiate birth related pulmonary vasodilator stimuli and could improve conditions associated with failure to circulatory adaptation at birth.

Oral sildenafil in the treatment of erectile dysfunction in diabetic men: A randomized double-blind and placebo-controlled study

Purpose: To determine the efficacy and safety of oral sildenafil citrate in the treatment of erectile dysfunction (ED) in diabetic men. Materials and methods: In a randomized, double-blind, placebo-controlled, and fixed-dose study, a total of 282 men (mean age, 46.4 years) with ED (mean duration, 3.6 years) and diabetes (mean duration, 11 years) were randomly assigned to receive 100 mg sildenafil ( n=144) or placebo ( n=138) approximately 1 h before planned sexual activity, but not more than once daily, for 16 weeks. The efficacy of two treatments was assessed using responses to the International Index of Erectile Function (IIEF) questionnaire. Results: Two hundred sixty-two (93%) of men completed the study (134/144 in the sildenafil group, 128/138 in the placebo group). Positive clinical results were obtained in 68 (51%) of 134 patients in the sildenafil group compared with 14 (11%) of 128 patients in the placebo group ( P<.003). Fifty-nine percent of the patients reported at least one successful attempt at sexual intercourse in the sildenafil group as compared with 21% successful attempts for the placebo group ( P<.002). Drug-related adverse effects occurred in 32 (22%) of 144 patients taking sildenafil and 4 (3%) of 138 patients receiving placebo. The most common adverse events were headache (20% sildenafil, 2% placebo), flushing (19% sildenafil, 0% placebo), dyspnea (9% sildenafil, 2% placebo), rhinitis (6% sildenafil, 0% placebo), and cardiovascular effects (7% sildenafil, 0% placebo). Of patients taking sildenafil, four (2.7%) developed new chest pains, with documented myocardial infarction in two. Conclusion: Oral sildenafil is a moderately effective treatment for ED in men with diabetes. The response rate was lower and cardiovascular events were higher than previously reported in nondiabetic patients.

Visual short-term effects of viagra: double-blind study in healthy young subjects

Purpose To investigate short-term visual effects of a single 100-mg dose of Viagra (sildenafil citrate) in healthy men. Design Randomized, double-blind, placebo-controlled clinical trial of drug effects on normal volunteers conducted by a single center. Methods Twenty men, aged 20 to 40 years, were treated with either a placebo or 100 mg sildenafil. Visual function tests included electroretinogram (ERG) recordings, on-/off- and 3.3 Hz-flicker-ERG recordings, anomaloscope matches, and measurements of cone contrast sensitivities and transient tritanopia. Results Most visual tests did not differ between the sildenafil and placebo groups. However, statistically significant increases in sensitivity during transient tritanopia were observed as well as significant prolongations in the implicit times of scotopic a-wave, photopic b-wave, and 3.3 Hz-flicker a-wave and b-wave ERG recordings. The magnitude of the differences correlated with peak sidenafil plasma concentration. Although rod amplitudes of the ERG recordings tended to be higher and cone amplitudes lower in the sildenafil group after drug ingestion, the differences were nonsignificant. There were no reports of visual side effects, and all electrophysiologic and psychophysical measurements returned to the normal range within 24 hours. Conclusions A single oral dose of 100-mg sildenafil given to healthy young men led to small but statistically significant transient changes of outer and inner retinal function, as detected by ERG and psychophysical methods. Although the acute effects were fully reversible within 24 hours, it would be worthwhile to compare them with those induced by other PDE5 and PDE6 inhibitors.

Sildenafil (Viagra) reduces arrhythmia severity during ischaemia 24 h after oral administration in dogs.

Sildenafil (Viagra) prolongs repolarisation in cardiac muscle, an effect that could lead to ventricular fibrillation (VF). Sildenafil (2 mg kg(-1)) was given by mouth to 12 mongrel dogs and, 24 h later, these dogs were anaesthetised, thoracotomised and subjected to a 25 min occlusion of the anterior descending coronary artery. Haemodynamic parameters were similar in this and the control group, but there were fewer and less serious ventricular arrhythmias during occlusion in the sildenafil group (VF 17 vs 60%; ventricular premature beats 140+/-52 vs 437+/-127% and episodes of ventricular tachycardia 4.0+/-3.2 vs 19.3+/-7.7%, all P<0.05). However, reperfusion VF and indices of ischaemia severity (epicardial ST-segment mapping, inhomogeneity) were not modified by the drug. Sildenafil increased the QT interval, especially during ischaemia. Our conclusion is that ischaemia-induced ventricular arrhythmias are reduced by sildenafil, but this protection is less pronounced than that following cardiac pacing or exercise.

Effect of PDE5 inhibition combined with free oxygen radical scavenger therapy on erectile function in a diabetic animal model.

Phosphodiesterase (PDE) inhibitors represent an important advance in the treatment of erectile dysfunction (ED). In spite of widespread use and generally good efficacy, as a class they remain ineffective in 15-57% of men. Specific cohorts of patients with severe vascular or neurogenic basis to their ED, such as diabetic men or those who have undergone radical pelvic surgery, demonstrate lower response rates with PDE inhibition treatment. We believe that circulating levels of nitric oxide (NO) may be enhanced through delivery of adequate concentrations of free oxygen radical scavenger molecules such as vitamin E. Higher levels of NO, theoretically, should produce increased penile blood flow with the potential for a synergistic effect when combined with a PDE5 inhibitor. With this hypothesis in mind, 20 adult male Sprague-Dawley streptozotocin-induced (60 mg/kg i.p.) diabetic rats were divided into four therapeutic groups (n=5). Group I--control animals received peanut oil, group II--vitamin E 20 IU/day, group III--sildenafil 5 mg/kg/day and group IV--vitamin E 20 IU/day plus sildenafil 5 mg/kg/day, by oral gavage daily for 3 weeks. Erectile function was assessed as a rise in intracavernous pressure following cavernous nerve electrostimulation. Penile tissue was harvested to determine the changes in tissue morphology including neuronal nitric oxide synthase, smooth muscle alpha-actin and endothelial cell integrity. PDE5 protein content and activity were measured. Significant increases in intracavernous pressure were measured in the animals receiving combined vitamin E plus sildenafil treatment. Immunohistochemical staining showed increases of neuronal nitric oxide synthase, endothelial cell and smooth muscle cell staining. Western blot analysis did not show significant differences of PDE5 protein between the groups. However, higher PDE5 activity was measured in the sildenafil group and lower activity of PDE5 was recorded in the cohort receiving vitamin E with sildenafil. Vitamin E enhanced the therapeutic effect of the PDE5 inhibitor in a meaningful way in this animal model of diabetes. This study indicates a potential means of salvaging erectile function among patients who are refractory to sildenafil.

Effects of Sildenafil Citrate (Viagra) on Choroidal Congestion

This study evaluates the effect of sildenafil on choroidal vascular congestion and its correlation with visual effects. Thirteen healthy subjects were randomized to a sildenafil group (n = 7, 3 M, 4 F), who received 200 mg of sildenafil, and a control (n = 6, 5 F, 1 M) group, who received no drug. Measurements of choroidal thickness with ultrasonography, color vision with Desaturated Panel D-15 Test, and contrast sensitivity with CSV-1000e charts (Vector Vision) were performed at baseline and at 90 and 180 min. Mean choroidal thickness and contrast sensitivity did not change significantly relative to baseline in either group. However, the variance in differences between repeat and baseline measurements of choroidal thickness was significantly higher at 90 min (p = 0.003) in the sildenafil subjects. Color discrimination error scores increased after sildenafil but did not correlate with changes in choroidal thickness. An oral dose of 200 mg of sildenafil caused small inconsistent changes in choroidal thickness, which did not correlate with visual effects.

Efficacy of Oral Sildenafil in Hemodialysis Patients with Erectile Dysfunction

The aim of this study was to evaluate the efficacy and safety of oral sildenafil to treat erectile dysfunction (ED) in chronic renal failure in patients on hemodialysis (HD). A double-blind, randomized, placebo-controlled study of oral sildenafil (50 mg) administered as required in HD patients with ED was designed. Patients on HD for at least 6 mo and who had a stable relationship with a female sexual partner were included. Patients older than 70 yr with penile anatomic abnormalities, cirrhosis, diabetes, angina, severe anemia, and those who were on nitrate treatment or with a recent history of stroke or myocardial infarction were not included. The International Index of Erectile Dysfunction (IIEF) was employed to evaluate ED and treatment response. Forty-one patients were evaluated (21 received placebo, and 20 sildenafil). Baseline clinical and demographic parameters were similar in both groups. Sildenafil was associated with improvement in the score of all questions and domains of the IIEF, except those related to sexual desire. Using the erectile function domain to evaluate primary efficacy, improvement was observed in 85% of the sildenafil patients compared with 9.5% of placebo patients. Sildenafil use resulted in normal EF scores in 35% of sildenafil patients. Sildenafil was well tolerated. Headaches and flushing occurred in both groups. Dyspepsia was reported by two patients in the sildenafil group. In conclusion, oral sildenafil seems to be an effective and safe treatment for ED in selected patients with chronic renal failure on hemodialysis.

Efficacy and safety of sildenafil citrate (Viagra ®) in black and Hispanic American men

The objective of this study was to assess the efficacy and safety of sildenafil citrate (Viagra) in black American and Hispanic American men with erectile dysfunction (ED) of broad-spectrum etiology. A total of 246 black American and 197 Hispanic American men were randomized to sildenafil (50 mg, adjustable to 25 mg or 100 mg, depending on efficacy and tolerability; n = 124 and n = 99, respectively) or matching placebo (n = 122 and n = 98, respectively). After 6 weeks, patients were given the option of switching to the other blinded treatment for the following 6 weeks. The 12 weeks of double-blind treatment were followed by 12 weeks of open-label extension. Despite differences in prevalence of hypertension, diabetes mellitus, hyperlipidemia, and use of concomitant antihypertensive agents between the 2 study groups, sildenafil was efficacious and well tolerated. After 6 weeks, scores for questions 3 and 4 from the International Index of Erectile Function (IIEF) were significantly higher among sildenafil-treated black and Hispanic patients than in placebo-treated patients. In addition, compared with placebo, a significantly larger proportion of sildenafil patients reported improved erections and improved ability to have sexual intercourse. When efficacy results were stratified by ED severity or number of risk factors, scores for IIEF questions 3 and 4 were lower in men with severe ED versus mild-to-moderate ED. Similarly, the percentage of patients reporting improved erections decreased with ED severity and number of risk factors. The proportion of patients switching to the other treatment after 6 weeks was significantly higher in the placebo group (71% to 85%) than in the sildenafil group (27% to 28%). The most common adverse events included headache and vasodilation, which were mild to moderate in nature and were comparable between groups. These data demonstrate that despite differences in prevalence rates of comorbidities, efficacy and safety of sildenafil is maintained across different ethnic groups.

Introduction

Introduction

Effects of Sildenafil Citrate on Sodium Nitroprusside and Nitroglycerin-Induced Hypotension in Dogs

Background: Nitrovasodilators are known to induce hypotension through activating nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway. By inhibiting the breakdown of cGMP, sildenafil citrate may augment the nitrovasodilator-induced hypotension. The present study was aimed to investigate whether sildenafil would reduce the dose of nitrovasodilators needed to induce the hypotension. Methods: Ten mongrel dogs were acutely instrumented with a femoral artery catheter and a pulmonary artery catheter. They were intravenously given sodium nitroprusside (SNP; 1-16/kg/min) or nitroglycerin (NTG; 2-32/kg/min) to induce hypotension. The study was composed of two occasions in each animal: one with sildenafil pretreatment (1 mg/kg IV followed by 0.3 mg/kg/h) and the other without to serve as control, one week apart. Hemodynamic parameters were continuously monitored. Plasma cGMP concentrations were measured by radioimmunoassay. Results: Both SNP and NTG produced dose-dependent reductions in mean arterial pressure (MAP) without affecting the heart rate in both the control and sildenafil groups. Systemic vascular resistance index (SVRI) and mean pulmonary arterial pressure were also decreased. However, SNP caused a greater reduction of MAP and SVRI in the sildenafil group than in the control group; whereas, NTP caused similar reductions in both groups. Neither SNP nor NTG altered the plasma cGMP concentrations. Sildenafil increased the plasma cGMP concentration, which was further increased by SNP, but not by NTG. Conclusions: These results indicate that sildenafil may reduce the dose of SNP, but not that of NTG needed to produce hypotension in the dog. The potentiation of SNP-induced hypotension by sildenafil may be related to an augmented cGMP effect.

Evaluation of side effects of sildenafil in group of young healthy volunteers.

We evaluated the safety and side effects of sildenafil in a group of sexually active volunteers younger than 40 years under conditions without sexual stimulation. Single oral dose of 50 mg dildenafil (n = 20) or placebo (n = 20) was randomly administered to 40 sexually active volunteers with the mean age of 26.80 +/- 5.29 in sildenafil group and 25.70 +/- 4.95 in placebo group. All the subjects were informed about the study, but not about the medicine. The following tests were performed immediately before and 90 minutes after the administration of the medicine: resting heart rate, blood pressure, electrocardiogram, visual acuity, color vision. The subjects were also asked to describe any discomfort or difference. Mann Whitney U test was used for statistical analyses. The only statistically significant difference was between heart rates before and after the administration of the sildenafil (p = 0.02). Color vision, visual acuity tests yielded no differences. The decrease in blood pressure was not significant. The most common side effects were flushing (75% and 0%), headache (50% and 5%), dyspepsia (15% and 5%), unintentional incomplete sexual arousal (15% and 0%) and palpitation (15% and 10%) in groups of sildenafil and placebo, respectively. The only serious side effect requiring medical treatment was arthralgia on the knee in one subject. Although these side effects can be acceptable, the likelihood of these side effects needs to be made clear to potential users of this medication.

Effect of sildenafil in patients with erectile dysfunction taking antihypertensive therapy

Oral sildenafil is an effective treatment for erectile dysfunction (ED), which is a common complaint for patients with hypertension and those taking antihypertensive agents. This post hoc subanalysis assessed the efficacy and safety of sildenafil in men with ED who were receiving concomitant antihypertensive medication. Efficacy was assessed in 3414 men (1218 of whom were taking antihypertensive medication) who received sildenafil (5 to 200 mg) or placebo for 6 weeks to 6 months in 10 double-blind, placebo-controlled studies. The significant improvements in erectile function demonstrated by sildenafil-treated patients were comparable in patients taking and those not taking antihypertensive medication. Safety was assessed in 3975 men (1094 of whom were taking one or more antihypertensive agent, classified as a diuretic, β-blocker, α 1-blocker, angiotensin converting enzyme inhibitor, or calcium channel blocker), who received sildenafil or placebo in 18 double-blind, placebo-controlled studies. For patients taking sildenafil and antihypertensive medication, the incidence of treatment-related adverse events (34%) was similar to that for sildenafil-treated patients not taking any antihypertensive agent (38%). The incidences of the most common adverse events and of adverse events potentially related to blood pressure decreases (eg, hypotension, dizziness, and syncope) were similar in both sildenafil groups. The number of antihypertensive medications taken from among the five classes had no effect on the adverse event profile of sildenafil. Sildenafil is an effective and well-tolerated treatment for ED in patients taking concomitant antihypertensive medication, including those on multidrug regimens.

Efficacy and safety of sildenafil citrate in the treatment of erectile dysfunction in patients with ischemic heart disease

Erectile dysfunction is a common condition in men with cardiovascular disease, probably as a result of shared factors that impair hemodynamic mechanisms in the penile and ischemic vasculature. Sildenafil citrate, an orally active, selective inhibitor of phosphodiesterase type 5 (PDE5), has demonstrated excellent efficacy and safety profiles in men with erectile dysfunction of various etiologies. Sildenafil administration is contraindicated in patients who are taking nitrates or nitric oxide donors. This retrospective subanalysis of data from double-blind, placebo-controlled studies assessed the efficacy (9 studies) and safety (11 studies) of sildenafil in patients with erectile dysfunction and ischemic heart disease who were not taking nitrates. Of 3,672 patients randomized to receive sildenafil (5–200 mg) or placebo for 4–24 weeks in 11 double-blind, placebo-controlled studies, 357 (10%) reported a history (past or present) of ischemic heart disease and were not taking nitrates. Efficacy was assessed using end-of-treatment responses to Question 3 (ability to achieve an erection) and Question 4 (ability to maintain an erection) of the International Index of Erectile Function (IIEF), scores for the 5 domains of male sexual function assessed by the IIEF (erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction), and responses to a global efficacy question (“Did the treatment improve your erections?”). The responses to the 2 IIEF questions were graded on a scale of 1 (almost never or never) to 5 (almost always or always), with a score of 0 indicating no attempt at sexual intercourse. At the end of treatment, the mean scores for Question 3 and Question 4 of the IIEF for patients with erectile dysfunction and ischemic heart disease were significantly higher for the sildenafil group than for the placebo group (p <0.0001). Mean end-of-treatment scores for the IIEF domains also demonstrated significant increases for sildenafil-treated patients compared with those receiving placebo (p <0.05). At the end of treatment, improved erections were reported by 70% of patients who received sildenafil and by 20% of those in the placebo group (p <0.0001). For the sildenafil group, the incidences of the most common adverse events (headache 25%, flushing 14%, and dyspepsia 12%) for patients with ischemic heart disease were similar to those in patients without this concomitant illness (21%, 15%, and 10%, respectively). Moreover, the overall incidence of cardiovascular adverse events other than flushing was comparable in patients with and without ischemic heart disease for both treatment groups. Since there is a degree of cardiac risk associated with sexual activity, clinicians should consider the patient’s cardiovascular status before initiating any treatment for erectile dysfunction. Physicians should be aware that patients with underlying cardiovascular disease could be adversely affected by the vasodilator effects of sildenafil, especially in combination with sexual activity. The results of the present subanalysis indicate that oral sildenafil significantly improves erectile function and is well tolerated in patients with erectile dysfunction and ischemic heart disease who are not taking nitrate therapy.