A classification based on peak systolic velocity and end diastolic velocity predicts Sildenafil Citrate (Viagra) success.

OBJECTIVE: To attempt to predict the success rate of Sildenafil Citrate (Viagra) in Erectile Dysfunction patients using penile Doppler ultrasonography (PDU) measurements of peak arterial velocity and end diastolic velocity. MATERIAL AND METHODS: A total of 212 patients (age range 27-76 years) with vascular pathologies were included in the study. Following a PDU test, the patients were divided into arterial insufficiency, veno-occlusive dysfunction and mixed vascular pathology groups. Subsequently, patients were given Sildenafil Citrate (Viagra) 50 mg and re-evaluated 1 month later to determine its efficacy. If it was ineffective, the dose was increased to 100 mg and patients were reassessed. Arterial insufficiency and veno-occlusive dysfunction patients were classified into mild, moderate and severe groups depending on peak systolic and end diastolic velocities. RESULTS: The overall response rate in patients with arterial insufficiency was 74.5%, regardless of the degree of arterial insufficiency or the dose of sildenafil. The severe arterial insufficiency group had a much better response to 100 mg compared to 50 mg doses of sildenafil. Although the 50 mgSildenafil Citrate (Viagra) dose was effective in patients with minimal veno-occlusive dysfunction, 100 mg was better than 50 mg to achieve adequate erection in the mild and severe veno-occlusive dysfunction groups. CONCLUSIONS:Sildenafil Citrate (Viagra) was ineffective in patients with severe arterial and venous insufficiency. PDU and a simple classification of PDU velocity measurements can provide some important clues to the prognosis of treatment and avoid overtreatment and unnecessary office visits

Oxidative stress and antioxidant therapy: their impact in diabetes-associated Erectile Dysfunction.

Oxidative stress is believed to affect the development of diabetic-associated vasculopathy, endothelial dysfunction, and neuropathy within erectile tissue. Our hypothesis is that, given adequate concentrations of the oxygen free radical scavenger vitamin E, enhanced levels of circulating nitric oxide (NO) should improve erectile function with the potential for a synergistic effect with a phosphodiesterase type 5 (PDE5) inhibitor. Twenty adult male Sprague-Dawley streptozotocin-induced (60 mg/kg intraperitoneally) diabetic rats were placed in 4 therapeutic groups (n = 5 per group) as follows: 1) peanut oil only (diabetic control), 2) 20 IU of vitamin E per day, 3) 5 mg/kg ofSildenafil Citrate (Viagra) per day, and 4) vitamin E plusSildenafil Citrate (Viagra) using oral gavage for 3 weeks. In addition, 5 age-matched rats served as normal nondiabetic controls (normal). Erectile function was assessed by measuring the rise in intracavernous pressure (ICP) following cavernous nerve electrostimulation. Penile tissue was evaluated for neuronal NO synthase (nNOS), smooth muscle alpha-actin, nitrotyrosine, and endothelial cell integrity. Urine nitrite and nitrate (NOx) concentration was quantified, and electrolytes were tested by a serum biochemistry panel. A significant decrease in ICP was recorded in the diabetic animals, with improvement measured in the animals receiving PDE5 inhibitors either with or without vitamin E; the controls had a pressure of 54.8 +/- 5.3 cm H2O, the vitamin E group had a pressure of 73.5 +/- 6.6 cm H2O, theSildenafil Citrate (Viagra) group had a pressure of 78.4 +/- 10.77 cm H2O, and the vitamin E plusSildenafil Citrate (Viagra) group had a pressure of 87.9 +/- 5.5 cm H2O (P <.05), compared with the normal cohorts at 103.0 +/- 4.8 cm H2O. Histoexaminations showed improved nNOS, endothelial cell, and smooth muscle cell staining in the vitamin E plusSildenafil Citrate (Viagra) group compared to the control animals. Urine NOx increased significantly in all the diabetic groups but was blunted in the vitamin E and vitamin E plusSildenafil Citrate (Viagra) groups. A significant increase in positive staining for nitrotyrosine was observed in the vitamin E plusSildenafil Citrate (Viagra) group. Vitamin E enhanced the therapeutic effect of the PDE5 inhibitor in this study, supporting the potential use of oxygen free radical scavengers in salvaging erectile function in diabetic patients

Efficacy ofSildenafil Citrate (Viagra) in Erectile Dysfunction after radical prostatectomy.

Radical retropubic prostatectomy (RRP) is an important cause of iatrogenic Erectile Dysfunction (ED). WhileSildenafil Citrate (Viagra) has been widely used since its introduction as a new treatment option for ED, its efficacy in post-RRP patients has not been extensively studied. We retrospectively compared the efficacy ofSildenafil Citrate (Viagra) in post-RRP and non-surgical patients with ED (NSED) using a subset of questions from the International Index of Erectile Function (IIEF) and correlated results with their specific etiology of ED based on penile blood flow study (PBFS). A brief questionnaire regarding satisfaction withSildenafil Citrate (Viagra) was administered to 72 consecutive post-RRP patients (nerve sparing status unknown) and 32 consecutive NSED patients who had previously undergone PBFS with pharmacotesting as part of their evaluation for ED. PBFS diagnoses were arterial insufficiency (AI) for peak systolic velocity (PSV) < 25 cm/sec; venogenic (CVOD) for PSV > or = 35 cm/sec, mixed vascular for PV > 25 but < 35 cm/sec and resistive index (RI) < 0.9; a vascular normal diagnosis (neurogenic impotence) required excellent rigidity sustained for 20 min. Differences in the IIEF subscores for the different groups of patients were assessed. Success withSildenafil Citrate (Viagra) was defined as moderate or excellent improvement (3/4 or 4/4) with ability for penetration. No differences were found among the different subgroups of RRP patients with respect to IIEF scores or success rates with sildenafil. NSED patients had both significantly higher post-treatment IIEF scores (3.6/3.4 vs 2.5/2.2; t=4.50, P<0.0001) and success rates (63% vs 31%; t=3.11, P < 0.01) withSildenafil Citrate (Viagra) treatment than RRP patients. We found thatSildenafil Citrate (Viagra) is significantly less effective in impotent RRP patients than in age-matched patients with ED (31% vs 63%). We had postulated thatSildenafil Citrate (Viagra) would be least effective among RRP patients with excellent sustained rigidity to PGE1, as this subgroup is likely to have neurogenic impotence. We found thatSildenafil Citrate (Viagra) response rates among subgroups of RRP patients were statistically similar regardless of PBFS diagnosis. IIEF scores for the RRP subgroups were similar but statistically lower than in men with ED and no history of RRP. While individuals with normal vascular responses to PGE1 have an increased likelihood of having neurogenic impotence, in RRP patients, we were unable to demonstrate any difference in efficacy of sildenafil, regardless of the PBFS diagnosis

Algorithm for diagnosis and treatment of Erectile Dysfunction in the era of Sildenafil Citrate (Viagra).

Since Viagra (Sildenafil Citrate (Viagra)) was released as a pharmaceutical agent for the treatment of Erectile Dysfunction, it has had a big impact on the work undertaken in our practice. I herewith present an algorithm for the diagnosis and treatment of Erectile Dysfunction in the era of Sildenafil Citrate (Viagra)

Sildenafil-induced peripheral analgesia and activation of the nitric oxide-cyclic GMP pathway.

Although several lines of evidence have shown a role of the nitric oxide/cyclic guanosine monophosphate signaling pathway in the nociceptive mechanism, the exact role of the phosphodiesterase (PDE) 5 enzyme via the NO-cGMP pathway is not fully understood in pain response. The present study was aimed at exploring the role of the NO-cGMP pathway in nociceptive conditions in experimental animals. Peripheral nociception was assessed by acetic acid-induced chemonociception or carrageenan-induced hyperalgesia and central nociception was assessed by tail-flick and hot-plate methods.Sildenafil Citrate (Viagra) exhibited dose-dependent (1, 2, 5 and 10 mg/kg, i.p.) antinociception in both male and female mice against acetic acid-induced writhing. However, it did not alter the pain threshold in central nociception (5 and 10 mg/kg, i.p.). Local administration ofSildenafil Citrate (Viagra) (50-200 microg/paw, i.pl) also attenuated carrageenan-induced hyperalgesia. In the peripheral nociceptive reaction (acetic acid-induced chemonociception), the antinociceptive effect ofSildenafil Citrate (Viagra) (2 mg/kg, i.p.) was enhanced by co-administration of sodium nitroprusside (0.25 mg/kg), and L-arginine (50 mg/kg). Sildenafil-induced analgesia was significantly blocked by methylene blue (1 mg/kg), a guanylate cyclase inhibitor, but was not reversed by L-NAME (10 mg/kg), a nitric oxide synthase inhibitor. But a higher dose of L-NAME (20 mg/kg) significantly reversedSildenafil Citrate (Viagra) analgesia. Both of these agents also reversed the facilitatory effect of L-arginine (50 mg/kg) and sodium nitroprusside (0.25 mg/kg) onSildenafil Citrate (Viagra) analgesia. These results suggest that sildenafil-induced analgesia is mediated via the inhibition of PDE5. The results also indicate that the guanylate cyclase system is stimulated in the peripheral nociceptive reaction. In conclusion,Sildenafil Citrate (Viagra) produces antinociception and its effect can be potentiated by sodium nitroprusside and L-arginine, probably through the activation of the NO-cyclic GMP pathway

Stimulation of the nitric oxide-guanosine 3', 5'-cyclic monophosphate pathway by sildenafil: effect on rectal muscle tone, distensibility, and perception in health and in irritable bowel syndrome.

OBJECTIVES: Nitric oxide, a neurotransmitter in the noncholinergic, nonadrenergic nervous system, is a mediator of relaxation of GI smooth muscle and of visceral nociception mainly studied in vitro.Sildenafil Citrate (Viagra) stimulates the nitric oxide guanosine 3', 5'-cyclic monophosphate (NO-cGMP) pathway through inhibition of phosphodiesterase 5. The aims of this study were to evaluate in vivo the effect of stimulation of the NO-cGMP pathway on rectal tone, distensibility, and perception in healthy individuals and in patients with irritable bowel syndrome (IBS). METHODS: In eight healthy subjects and four patients with IBS rectal tone, distensibility and perception thresholds were measured with an electronic barostat both before and 60 min after administration ofSildenafil Citrate (Viagra) (50 mg p.o.). Perception was scored on a graded scale of 0-6. At the end of a distension series an anatomic questionnaire was filled out by the subjects. RESULTS:Sildenafil Citrate (Viagra) significantly reduced rectal tone in healthy subjects (intrabag volume predrug: 145.5 +/- 18.7 ml vs postdrug: 164.4 +/- 16.9 ml, p = 0.01) and IBS (111.3 +/- 25.2 ml vs 136.5 +/- 33.3 ml; p = 0.01) but did not alter rectal compliance (healthy subjects: 5.8 +/- 0.4 vs 6.3 +/- 0.6 ml/mm Hg, p > 0.05; IBS subjects: 6.1 +/- 0.6 vs 7.1 +/- 1.0 ml/mm Hg, p > 0.05). Intrabag pressure and rectal wall tension to reach perception thresholds for initial sensation, sensation of stool, and urgency were not altered by sildenafil. However, intrabag volumes to reach these thresholds were significantly increased bySildenafil Citrate (Viagra) both in healthy subjects and in patients with IBS. Viscerosomatic referral was unchanged. CONCLUSIONS: Stimulation of the NO-cGMP pathway decreases rectal tone but does not influence rectal distensibility. Relaxation of the rectum is accompanied by an increase in rectal volumes to reach perception thresholds in healthy subjects and in patients with IBS, but no direct effect on rectal perception can be demonstrated

Sildenafil Citrate (Viagra) does not affect cardiac contractility in human or dog heart.

OBJECTIVE: This study evaluated whether Sildenafil Citrate (Viagra), an oral treatment for Erectile Dysfunction and a selective inhibitor of phosphodiesterase type 5 (PDE5) with modest vasodilating properties, affects cardiac contractility in vitro. Research design and methods: Slices of freshly obtained human (n = 2) or dog (n = 3) atrial appendage were suspended in organ baths containing Krebs-Ringer bicarbonate buffer (pH 7.4, 37 degrees C) bubbled continuously with 95% O2 and 5% CO2, and isometric tension was recorded using a Gould physiograph. Contractions were elicited by 1-Hz electric pacing. After 15 min of equilibration, 1 microMSildenafil Citrate (Viagra) was added to the bath, followed 15 min later (human and dog) by 5 microM epinephrine, an inotropic agent, and 10 min later (dog) by 88 microM 3-isobutyl-1-methylxanthine (IBMX), a nonselective PDE inhibitor. In a separate experiment, cyclic guanosine monophosphate levels and PDE, protein kinase G, and protein kinase A activities were determined. RESULTS: Addition of 1 microMSildenafil Citrate (Viagra) to isolated dog or human atrial tissue had no significant effect on force of cardiac contraction, whereas epinephrine produced a robust increase in contractile force in the same muscle strip. The addition of IBMX produced a marked stimulation of contractile force in dog atrial tissue. Very low amounts of PDE5 were found in extracts of human heart, consistent with its known primary location in the smooth muscle of systemic vasculature. CONCLUSIONS:Sildenafil Citrate (Viagra) is unlikely to directly produce inotropic effects on cardiac muscle in patients being treated for Erectile Dysfunction

Acute effects ofSildenafil Citrate (Viagra) in patients with primary pulmonary hypertension receiving epoprostenol.

Epoprostenol therapy has improved survival in primary pulmonary hypertension; however, only two thirds of patients are alive 3 years after starting treatment. Combined therapy with sildenafil, a phosphodiesterase 5 inhibitor, may provide additional benefit. The authors prospectively evaluated the acute hemodynamic and biochemical effects ofSildenafil Citrate (Viagra) and inhaled nitric oxide, alone and in combination, in 8 patients with primary pulmonary hypertension receiving chronic epoprostenol. Average duration of epoprostenol therapy was 2.9 +/- 1.6 years (mean +/- SD) and mean dose was 25.7 +/- 10.8 ng/kg/min. A single 50 mg dose ofSildenafil Citrate (Viagra) decreased mean pulmonary arterial pressure 10% (P<.05), increased cardiac output 8%, and decreased pulmonary vascular resistance 24% (P<.005). Although nitric oxide led to a similar decrease in mean pulmonary arterial pressure of 10% (P<.05), cardiac output was unchanged, resulting in a decrease in pulmonary vascular resistance of only 13%, which was not statistically different from baseline. These results suggest thatSildenafil Citrate (Viagra) has greater acute hemodynamic effects than nitric oxide and that it can further reduce pulmonary vascular resistance in patients already demonstrating a benefit from chronic epoprostenol