Evaluation and therapeutic regulation of erectile dysfunction with visual stimulation test. An objective approach by using sildenafil citrate test.

Erbagci A, Yagci F, Sarica K, Ozbek E, Topcu O.

Department of Urology, Sahinbey Hospital, University of Gaziantep, Medical School Gaziantep, Turkey. gantepuro hotmail.com

AIM: An objective evaluation of the psychogenic cause of erectile dysfunction by performing the visual stimulation tumescence and rigidity (VSTR) test and sildenafil citrate test, together with the effectiveness of sildenafil citrate medication on impotence caused by different etiologies. MATERIAL AND METHODS: Between 1998 and 2000, a total of 36 men (12 patients with diabetic etiology, 5 patients with vasculogenic risk factor) were enrolled in this study. The mean age of patients was 53 (27-67) years. Following standard questionnaires, including a detailed anamnesis from an andrologic viewpoint, VST was performed in an ambulatory setting and beginning with a test dose of 50 mg. At the end of 2 h, the data was evaluated with computer assistance (Rigiscan device) and if a satisfactory erection had not occurred, an additional second dose of sildenafil citrate (50 mg) was given until there was a satisfactory erection. Results obtained from VST: results were classified as group I (fully rigidity, >10 min erection, >70% of rigidity, possible vaginal penetration), group II (unstable erection, 5 min erection, >70% of rigidity, possible vaginal penetration) and group III (tumescence without rigidity, <5 min erection, <70% of rigidity, impossible vaginal penetration). The results obtained during the first 1 h of the VSTR test were regarded as the patient's own erectile condition and later data was accepted as the real effect of sildenafil citrate. The Fisher exact test was used for statistical evaluation including pre- and post-sildenafil effect on erectile rigidity and duration of erection. RESULTS: The erection status of patients was sufficient in 17 (47.2%) in group I, it was insufficient but sufficient enough with an increased dose of sildenafil citrate in 10 (27.7%) in group II, and insufficient without/with full dose of sildenafil citrate in 9 (25%) in group III. Considering rigidity and total erectile period, there was a statistical significant difference between the first two groups with respect to the early and late sildenafil citrate effects on the VSTR test (p < 0.05). Again, 10 patients with known risk factors (diabetes mellitus 5 and vasculogenic 5) in the second group seemed to give a good response to repeated dosage of sildenafil citrate which has been found to be very interesting. However, the rest of the diabetic patients (n = 7) in the third group showed no erection despite the increasing and repeated doses of sildenafil citrate. CONCLUSION: Sildenafil citrate with the VSTR test has effective and reliable results which was regarded as very important to diagnose and determine objectively the amount of therapeutic doses in impotence. In accordance with the literature data, our results also confirm the reliability and the practical nature of the VSTR test, which is less time-consuming and cheaper than the nocturnal penile tumescence and rigidity (NPTR) test. In the VSTR test, necessary doses of medication needed for satisfactory erection were easily regulated in patients with certain kinds of impotence. Additionally, self-criticism advantage of the patients on erection and an unnecessary need for regular sexual partners may make this test preferable in the near future. However, we believe that a large group of patients with other definite parameters are certainly needed in order to obtain more reliable data. Copyright 2002 S. Karger AG, Basel

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12119434&dopt=Abstract sildenafil Viagra online



[The effects of sildenafil citrate on the isolated rat aorta: comparative in vitro study]

[Article in Turkish]

Ozbek H, Guler N, Aydin S, Eryonucu B, Bilge M.

Yuzuncu Yil Universitesi Tip Fakultesi Farmakoloji, Kardiyoloji. hanefiozbek hotmail.com

OBJECTIVE: Sildenafil, an inhibitor of cGMP-specific phosphodiesterase 5 (PDE5), is currently being used as oral therapy for penile erectile dysfunction. The aim of this study was to investigate the relaxing effect of sildenafil on vascular tissue and compare it with the known vasodilatator agents, sodium nitroprusside and acetylcholine. METHOD: Rat thoracic aorta samples were cut into rings, mounted on steel hooks, and immersed in aerated Krebs solution maintained at 37 degree C. Isometric responses were recorded by strain gauge transducers connected to a polygraph. Graded relaxations were induced using increasing concentrations of acetylcholine sodium nitroprusside and sildenafil. RESULTS: The agents all does-dependently relaxed rat aorta strips. The relaxing potential of sildenafil was found to be similar to sodium nitroprusside, but higher than acetylcholine. CONCLUSIONS: In the absence of regulatory mechanisms, sildenafil citrate has noticeable vasodilatatory effect in vitro.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12122968&dopt=Abstract sildenafil Viagra online



Effects of sildenafil on cardiac repolarization.

Chiang CE, Luk HN, Wang TM, Ding PY.

Division of Cardiology, Taipei Veterans General Hospital and National Yang-Ming University, 201, Sec 2, Shih-Pai Road, 112, Taipei, Taiwan. cechiang vghtpe.gov.tw

OBJECTIVES: Sudden death has occasionally been reported in patients taking sildenafil. The objective of this study was to investigate the effect of sildenafil on cardiac repolarization. METHODS: We used conventional microelectrode recording technique in isolated guinea pig papillary muscles and canine Purkinje fibers, whole-cell patch clamp techniques in guinea pig ventricular myocytes, and in vivo ECG measurements in guinea pigs. RESULTS: Action potential duration at 90% repolarization (APD(90)) was not affected by sildenafil in the therapeutic ranges (< or =1 microM), but shortened by higher concentration (> or =10 microM) in both guinea pig papillary muscles and canine Purkinje fibers. D-Sotalol prolonged APD(90) in the same preparations with concentrations > or =1 microM in a reverse frequency-dependent manner. Co-administration of sildenafil (10 and 30 microM) abolished the APD-prolonging effects of D-sotalol (30 microM) and amiodarone (100 microM). Sildenafil, with concentrations up to 30 microM, had no significant effect on both the rapid (I(Kr)) and the slow (I(Ks)) components of the delayed rectifier potassium currents in guinea pig ventricular myocytes. Sildenafil dose-dependently blocked L-type Ca(2+) current (I(Ca,L)), but had no effect on persistent Na(+) current in guinea pig ventricular myocytes. ECG recordings in intact guinea pigs revealed significant shortening of QTc interval by sildenafil (10 and 30 mg/kg orally). The QT-prolonging effects by D,L-sotalol (50 mg/kg) and amiodarone (100 mg/kg) were abolished by sildenafil (30 mg/kg). CONCLUSIONS: Sildenafil does not prolong cardiac repolarization. Instead, in supra-therapeutic concentrations, it accelerates cardiac repolarization, presumably through its blocking effect on I(Ca,L).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12123768&dopt=Abstract sildenafil Viagra online



Effects of two selective phosphodiesterase type 5 inhibitors, sildenafil and vardenafil, on object recognition memory and hippocampal cyclic GMP levels in the rat.

Prickaerts J, van Staveren WC, Sik A, Markerink-van Ittersum M, Niewohner U, van der Staay FJ, Blokland A, de Vente J.

Department of Psychiatry and Neuropsychology, European Graduate School of Neuroscience EURON, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands. jos.prickaerts np.unimaas.nl

The present study investigated the effects of two cyclic GMP-specific phosphodiesterase enzyme type 5 inhibitors, sildenafil and vardenafil, on the memory performance in the object recognition task. Both compounds were given per orally (1, 3 and 10 mg/kg sildenafil; 0.1, 0.3, 1 and 3 mg/kg vardenafil) immediately after the exposure to two identical objects. The memory for the objects was tested 24 h later. Vehicle-treated rats spent equal times exploring a new and the familiar object demonstrating that they did not remember the familiar one. However, sildenafil improved the object discrimination performance of the rats with a high discrimination performance at a dose of 3 mg/kg. Rats treated with vardenafil also showed an improved object discrimination performance. Compared with sildenafil, vardenafil appeared to be even more potent in this respect since it already produced a high discrimination performance at a dose of 0.3 mg/kg. The effects of both compounds on cyclic GMP and cyclic AMP accumulation were studied in rat hippocampal slices incubated in vitro. Cyclic GMP levels were increased after incubation with the highest concentration of 100 microM vardenafil (together with 0.1 mM sodium nitroprusside), although no changes in cyclic GMP levels were detected after incubation with different concentrations of sildenafil. Both compounds had no effect on cyclic AMP levels. Additional cyclic GMP immunocytochemistry showed that incubation with vardenafil (in the presence of sodium nitroprusside) resulted in a concentration-dependent staining of cyclic GMP. Staining was predominantly found in neuronal fibres in the hippocampal CA2/CA3 region. It was already detected at a concentration of 0.1 microM vardenafil. Also positive fibres were detected after incubation with sildenafil but at a higher concentration of 10 microM. Taken together, these results suggest that inhibition of phosphodiesterase enzyme type 5 improves object recognition memory. This effect might be explained by increased levels of central cyclic GMP. Copyright 2002 IBRO

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12127092&dopt=Abstract sildenafil Viagra online



The effect of sildenafil on electrostimulation-induced erection in the rat model.

Ueno N, Iwamoto Y, Segawa N, Kinoshita M, Ueda H, Katsuoka Y.

Department of Urology, Osaka Medical College, Takatsuki, Osaka, Japan.

This study was conducted to show the effect of sildenafil on electrostimulation-induced erection in the rat model. Fifteen 12-week-old male Wistar Kyoto rats were used. The intracavernous pressure and arterial blood pressure were simultaneously monitored through electric cavernous nerve stimulation before and after the administration of sildenafil (2 mg/kg). Statistical analysis was performed on maximal intracavernous pressure (MIP), mean arterial blood pressure (MAP), the MIP/MAP and detumescence time. MAP decreased significantly by about 20 mmHg after sildenafil administration. The MIP/MAP increased significantly after sildenafil administration. The effect of sildenafil on the MIP/MAP was marked especially at lower (2-3 Hz) frequencies. The detumescence time significantly increased after sildenafil administration. We have shown that sildenafil is effective for enhancing erection at lower frequencies and prolonging penile erection in rats. After the administration of sildenafil, penile erection would be induced by weak stimuli that will not cause penile erection under normal conditions.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12152113&dopt=Abstract sildenafil Viagra online



Incidence and determinants of sildenafil (dis)continuation: the Dutch cohort of sildenafil users.

Souverein PC, Egberts AC, Meuleman EJ, Urquhart J, Leufkens HG.

Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht, The Netherlands. P.C.Souverein pharm.uu.nl

Sildenafil utilization was prospectively evaluated among 153 men with a history of erectile dysfunction (ED)-prescription drug use prior to starting sildenafil and 164 men who were new starters of ED-prescription drugs. Further, some determinants of sildenafil discontinuation were identified. During a median follow-up period of 18 months 45% of all patients discontinued sildenafil treatment, regardless of earlier treatment history. However, patients with a history of drug treatment for ED were nearly eight times as likely to switch or re-start another ED-prescription drug after discontinuing sildenafil compared to previously untreated users. Age >60 y, diabetes medication, nitrate use, and use of incontinence pads (a proxy for disease/surgery in the pelvic region) were associated with an increased likelihood of discontinuing sildenafil. Although the introduction of sildenafil reduced the barrier to seek medical help for erectile problems, sildenafil treatment failure in previously untreated patients results in a high dropout rate from further ED drug treatment of any kind.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12152115&dopt=Abstract sildenafil Viagra online



Acute electroretinographic changes during sildenafil (Viagra) treatment for erectile dysfunction.

Balacco Gabrieli C, Regine F, Vingolo EM, Rispoli E, Isidori A.

Department of Ophthalmology, University of Rome La Sapienza, Rome, Italy. corrado.balacco uniroma1.it

The authors describe their findings on 12 subjects who were treated with 50 mg of sildenafil (Viagra) and underwent ERG measurements prior to and 1 hour after ingestion. The Naka-Rushton equation was used to describe the b-wave luminance-response function of the scotopic ERG. Statistically significant differences were noted in the Vmax and K values. Sildenafil ingestion resulted in an increase in Vmax (higher rod response to light stimuli) and a decrease in K (higher sensitivity).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14661900&dopt=Abstract sildenafil Viagra online



Efficacy and safety of sildenafil for treating erectile dysfunction in patients on dialysis.

YenicerioGlu Y, Kefi A, Aslan G, Cavdar C, Esen AA, Camsari T, Celebi I.

Department of Nephrology, Dokuz Eylul University, School of Medicine, Izmir, Turkey.

OBJECTIVE: To assess the efficacy of sildenafil for erectile dysfunction (ED) in patients on haemodialysis (HD) or peritoneal dialysis (PD), as men with end-stage renal disease (ESRD) often have sexual dysfunction (up to 82% among those on chronic dialysis). PATIENTS AND METHODS: Forty-one patients with ED and in ESRD participated in an open-label prospective study. Thirty patients on HD and 11 on PD were asked to complete the International Index of Erectile Function (IIEF) and Fugl-Meyer life-satisfaction scale before and after sildenafil treatment. A total score in the erectile function domain of < or = 25 was accepted as indicating ED. All patients were started on a 25-mg dose, which was increased to 50 mg if there was no response after two trials. In addition, the overall efficacy question was used to evaluate satisfaction, and patients reported any side-effects during treatment. RESULTS: The erectile function and intercourse satisfaction domains improved significantly in both groups (P < 0.01). After sildenafil treatment, two-thirds of those on HD (20/30) and nine of the 11 on PD recovered their erectile function. The pretreatment scores on the IIEF and four domains (except sexual desire) of those responding were significantly higher than in those not responding (P < 0.05). The satisfaction rate on the overall efficacy question was 80% and 82% for the HD and PD groups, respectively. At least one side-effect was seen in 17 patients (43%); one had severe hypotension in the PD group. Overall, mild headache (seven patients, 18%) and flushing (12, 30%) were reported most often. CONCLUSIONS: Sildenafil is a safe and satisfactory drug for improving erectile function in patients with ESRD. Patients were satisfied whether treated by HD or PD. Pretreatment scores on the IIEF may be useful for predicting the success of treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12175405&dopt=Abstract sildenafil Viagra online