sildenafil-citrate and Vascular-Diseases

In the past decade, impressive strides have been made in the diagnosis and management of atherosclerotic, aneurysmal, and thromboembolic diseases, thanks in large part to the explosive growth in both vascular biology and clinical vascular medicine. We review what we consider to be the top 12 advances in this field: the discovery of nitric oxide, the metabolic syndrome, new thrombophilic disorders, therapeutic angiogenesis, endoluminal treatment of chronic venous disease, and a variety of drugs, including sildenafil, cilostazol, low-molecular-weight heparins, oral direct thrombin inhibitors, clopidogrel, statins, and angiotensin-converting enzyme inhibitors and angiotensin-receptor blocking agents.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cilostazol; Clopidogrel; Factor V; Heparin, Low-Molecular-Weight; Hot Temperature; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Metabolic Syndrome; Mutation; Nitric Oxide; Phosphodiesterase Inhibitors; Piperazines; Platelet Aggregation Inhibitors; Purines; Sildenafil Citrate; Sulfones; Tetrazoles; Thrombin; Ticlopidine; Vascular Diseases; Vascular Surgical Procedures

The aim of the study was to establish and compare the efficacy and safety of sildenafil and apomorphine in men with arteriogenic erectile dysfunction (ED). In all, 43 men with ED and postinjection max penile systolic velocity <25 cm/s in repeated Doppler ultrasonography were included. Of these, 24 men started on apomorphine 2 mg and 19 on sildenafil 50 mg, the doses titrated up to 3 and 100 mg according to effectiveness and tolerability. Safety was evaluated according to adverse events (AEs) and patient withdrawal. Efficacy was the percentage of attempts resulting in erections firm enough for intercourse, based on event log data. The incidence of AEs with apomorphine 3 mg was higher than with sildenafil 100 mg. Two men on apomorphine 3 mg discontinued treatment due to AEs. The overall success rate of sildenafil was 63.7% compared to 32.1% of apomorphine (Pearson chi(2), P<0.01). Of all men, 25 (58.1%) responded to sildenafil 50 mg without the need for dose increase, while only one responded to apomorphine 2 mg. The response to sildenafil 50 mg was age related (analysis of variance, p=0.04). Satisfaction was reported by 76.75 and 13.95% of patients for sildenafil and apomorphine, respectively, but 20.9% were not satisfied with any of the two drugs. In conclusion, this study provides clear evidence that sildenafil, even at 50 mg dose, is more effective than apomorphine 3 mg in men with arteriogenic ED. The fact that one out of five patients is not satisfied with the above-studied drugs shows that new oral agents need to be evaluated for the treatment of this disorder.

Topics: Apomorphine; Arteries; Cross-Over Studies; Dopamine Agonists; Erectile Dysfunction; Humans; Male; Middle Aged; Patient Satisfaction; Piperazines; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Vascular Diseases; Vasodilator Agents

We compared the effectiveness of sildenafil citrate and alprostadil in improving arterial penile inflow (peak systolic velocity (PSV)) and penile rigidity in 55 patients with erectile dysfunction caused by atherosclerosis. A total of 35 patients with pure vasculogenic impotency were randomly assigned to alprostadil (Av group; n=11), sildenafil (Sv group; n=12), or placebo (P group; n=12), and 20 patients with nonvasculogenic impotency were randomly assigned to alprostadil (A group; n=10) or Sildenafil (S group; n=10): Av and A used alprostadil injection (capable of giving a full erection) once a week for 1 month, Sv and S took daily oral sildenafil (25 mg) for 1 month, and P took daily oral placebo for one month. The PSV was measured with Duplex sonography and penile rigidity was assessed using the IIEF-15 questionnaire, both of which were administered before and after treatment. Although both treatments improved penile rigidity, they increased PSV only in the Av and Sv groups. Our results suggest that alprostadil and oral therapy should be the starting therapy in men with vasculogenic impotency, whereas alprostadil should be avoided as the first-line approach in men with nonvasculogenic impotency.

Topics: Adult; Aged; Alprostadil; Arteries; Erectile Dysfunction; Humans; Male; Middle Aged; Piperazines; Placebos; Purines; Regional Blood Flow; Sildenafil Citrate; Sulfones; Treatment Outcome; Ultrasonography; Vascular Diseases; Vasodilator Agents

Endothelial dysfunction is a key early event in the process of atherosclerosis and a risk factor for cardiovascular events. Sildenafil, an effective oral treatment for patients with erectile dysfunction, inhibits cGMP degradation by specific type 5 phosphodiesterase (PDE) inhibition. Sildenafil has been shown to improve vascular function, however, the effect of type 5 PDE inhibition on acute smoking-induced endothelial dysfunction is unknown.. We studied the effect of 50 mg of sildenafil on acute smoking-induced endothelial dysfunction in 14 male smokers according to a randomized, placebo-controlled, cross-over design. Endothelial function was evaluated with flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasonography.. Sildenafil abolishes the decrease in FMD of the brachial artery that is induced acutely by smoking (placebo/smoking session: from 4.56% +/- 0.60% to 2.80% +/- 0.43%, sildenafil/smoking session: from 3.83% +/- 0.64% to 4.33% +/- 0.47%, ie, improvement of 51%, P < .05). This was associated with no reversal effect of sildenafil on smoking-induced decrease in resting brachial artery diameter and with a partial reversal of the smoking-induced decrease in hyperemic brachial artery diameter (placebo/smoking session: from 4.68 +/- 0.13 mm to 4.53 +/- 0.15 mm, sildenafil/smoking session: from 4.72 +/- 0.12 mm to 4.64 +/- 0.13 mm, ie, improvement of 1.5%, P < .005).. The present study shows, for the first time, that type 5 PDE inhibition with sildenafil abrogates the smoking-induced acute decrease in FMD of the brachial artery. These findings may have clinical implications given the detrimental consequences of smoking and the strategic role of normal endothelial function.

Topics: Acute Disease; Adult; Cross-Over Studies; Dilatation, Pathologic; Double-Blind Method; Endothelium, Vascular; Humans; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Smoking; Sulfones; Vascular Diseases; Vasodilation

Sildnenafil citrate is a powerful phosphodiesterase type 5 isoenzyme; it is the first oral treatment to have had a significant success in treatment of erectile dysfunction (ED). After oral dosing on an empty stomach the pharmacological activity starts within 30 to 120 minutes (average 60 minutes) whereas the effect of this medication after a meal could be notably delayed. We evaluated the start of pharmacological activity in 30 patients affected by non-psychogenic ED after sublingual administration of Sildenafil citrate.. Patients participating in our study were all affected by ED whose etiology was assessed as vasculogenetic or diabetic. The study lasted 6 months. For the first 3 months patients were asked to take Sildenafil (50-100 mg) for oral administration, under normal everyday conditions, 30 minutes before planned sexual relations. During the second 3 months the patients were asked to take Sildenafil for sublingual administration (crushing the pill in the mouth and dissolving the drug under the tongue) 15 minutes before planned sexual relations. The patients did not know the purpose of the study.. An appreciable reduction in the start of pharmacological activity was reported during the time of sublingual administration. In fact, while throughout the first 3 months the average pharmacological onset was 62.8 minutes (DS +/- 16.8), during the second 3 months it was 29.3 minutes (DS +/- 8.1), the mean difference in the start of pharmacological activity was 35.3 (DS +/- 12.4). The results of T-student test for paired observation were T (29) = 15.629; p-value 0.00001. During the two modalities of administration no differences were noted in the efficacy or in the frequency of adverse events. All the patients declared they preferred the sublingual way because of faster onset.. Even though ours is a limited study, our clinical data points out that the sublingual administration of Sildenafil is useful because of the rapid onset unrelated to meals. All the patients were reported to appreciate this method of administration, particularly in the case of unplanned sexual relations.

Topics: Administration, Oral; Administration, Sublingual; Aged; Diabetes Complications; Eating; Erectile Dysfunction; Fasting; Humans; Male; Middle Aged; Piperazines; Purines; Sildenafil Citrate; Sulfones; Time Factors; Treatment Outcome; Vascular Diseases

To retrospectively analyze the efficacy and safety of sildenafil (Sf) in patients with systemic sclerosis (SS).. Sf was used in 16 patients (including 14 women) aged 20-66 years (mean 48.6 +/- 14.6 years; median 51.5 years) with SS of a duration of 2 months to 27 years (mean 8.8 +/- 7.3 years; median 6.5 years). The indications for Sf treatment were significant Raynaud's phenomenon (RP) in 3 patients, digital ulcers (DU) and/or necroses (N) in 9, pulmonary hypertension (PH) in 5 (2 patients had PH concurrent with DU/N), and critical ischemia of the left fingers in 1 patient. RP was seen in all the patients and so the effect of Sf on the course of RP was evaluated in the whole patient group.. There was a significant decrease in the frequency and intensity of Raynaud's attacks in 11 (73%) of the 15 patients treated with Sf. This effect was obvious just in the first days of Sf treatment and remained stable throughout the treatment. No RP changes were seen in 3 patients. All 7 patients with DUs showed a decrease in their sizes just within the first two weeks of treatment. Complete DU healing was observed within 4-12 weeks of treatment. During a month, the necrotic area reduced and the signs of reparation appeared in 4 of the 6 patients. Pain ceased just within the first 5-7 days of treatment. Sf resulted in a rapid reduction in systolic pulmonary artery pressure (sPAP); in one case the latter diminished from 60 to 40 mm Hg just 90 min after the first intake of Sf 50 mg and remained unchanged during all 6 months during which the female patient was taking the drug. Doppler echocardiography showed that sPAP decreased from 103 to 85 mm Hg in another female taking Sf 100 mg for a month. The two cases showed clinical improvement as alleviated dyspnea and increased physical activity. In another case, Sf was discontinued because of dizziness after its first intake in a dose of 12.5 mg. The initial drug intake of the drug was not followed by adverse reactions in 12 (75%) of the 16 patients. Four patients had Sf-induced complaints, including headache (1), dizziness (2), and more severe angina pectoris (1). In different periods after treatment initiation, four more patients developed complications, such as fatal myocardial infarction after 6-week treatment, atrial fibrillation at 8 weeks, more severe angina at 6 months, and congestive heart failure after 5-year treatment. These complications were observed in patients with severe ECG changes, such as myocardial focal fibrosis or blood supply impairment.. Sf is an effective drug to treat the manifestations of scleroderma vasculopathy, such as RP, DU/N, and PH. Sf is well tolerated in most cases. The SS patients with pronounced ECG changes have an increased risk of severe cardiac events and they need careful ECG monitoring.

Topics: Adult; Aged; Drug Monitoring; Echocardiography, Doppler; Electrocardiography; Female; Humans; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Retrospective Studies; Scleroderma, Systemic; Sildenafil Citrate; Sulfones; Time Factors; Treatment Outcome; Vascular Diseases; Young Adult

This study evaluated the protective effect of sildenafil on liver injury induced by intestinal ischemia-reperfusion.. Forty female Sprague Dawley rats were divided into 4 groups: sham-control (SC), ischemia (I), ischemia-reperfusion (IR), and ischemia-reperfusion+sildenafil (SIL; sildenafil gavaged at 50mg/kg before operating). A 2-h ischemia-reperfusion was performed by clamping the superior mesenteric artery. Liver function, plasma alanine (ALT) and aspartate (AST) aminotransferase, and intestinal and liver malondialdehyde (MDA) were measured at the end of the experiment. Intestinal and liver tissue damage was examined by histology. Liver samples were immunologically stained for endothelial nitric oxide synthase (eNOS) and proliferating cell nuclear antigen (PCNA).. The ALT and AST levels were highest in the IR group and were lower in the SIL group (p<0.05). Intestinal MDA levels were statistically higher in the IR group than in the SC, I and SIL groups. Liver MDA levels were significantly higher in the IR group than in the I and SC groups (p<0.05) and higher than in the SIL group (p>0.05). Intestinal damage based on Chiu scoring was more severe in the IR than in the SIL group (p<0.05). Sildenafil reduced damage and also increased eNOS and PCNA immunoreactivity in liver tissue.. Sildenafil shows a protective effect on intestinal ischemia-reperfusion-induced liver injury, possibly by decreasing vascular resistance through increased nitric oxide levels.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Constriction; Drug Evaluation, Preclinical; Female; Intestines; Ischemia; Liver; Liver Glycogen; Malondialdehyde; Mesenteric Artery, Superior; Mesenteric Ischemia; Nitric Oxide; Nitric Oxide Synthase Type III; Oxidative Stress; Piperazines; Proliferating Cell Nuclear Antigen; Purines; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Sildenafil Citrate; Sulfones; Vascular Diseases; Vascular Resistance; Vasodilator Agents

Good status of pulmonary perfusion is essential for a successful outcome after the Fontan procedure. Increased pulmonary pressure and vascular resistance, small size of the pulmonary arteries, and significant branch stenoses reflect some of the main problems causing failing Fontan circulation. Here we report a child who underwent a staged Fontan procedure with subsequent subtotal loss of the left-sided pulmonary perfusion, although branch stenosis was successfully treated by stent implantation. Oral sildenafil caused restoration of the capillary vascular bed, improved left-sided lung perfusion, and resulted in significant clinical benefit.

Topics: Capillaries; Child, Preschool; Fontan Procedure; Heart Defects, Congenital; Humans; Lung; Male; Microcirculation; Piperazines; Pulmonary Circulation; Pulsatile Flow; Purines; Sildenafil Citrate; Sulfones; Vascular Diseases; Vasodilator Agents

Topics: Animals; Carbolines; Disease Models, Animal; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Male; Penile Erection; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Vascular Diseases; Vasodilator Agents

We report a case of successful administration of oral sildenafil (ie, a phosphodiesterase-5 inhibitor) in an infant for impaired pulmonary circulation that caused early clinical deterioration after a bicavopulmonary shunt. The transpulmonary pressure gradient (ie, a clinical indicator of pulmonary circulation) was initially normalized by inhaled nitric oxide; however, an increase in transpulmonary pressure gradient and oxygen desaturation occurred after extubation and discontinuation of inhaled nitric oxide on postoperative day 1. Subsequent administration of oral sildenafil in stepwise doses resulted in normalization of transpulmonary pressure gradient and improved oxygen saturation with successful discontinuation of intravenous vasodilators. Our results suggest that oral sildenafil may be a potent adjunctive therapy for impaired postoperative pulmonary circulation after right heart bypass surgery.

Topics: Administration, Oral; Heart Bypass, Right; Heart Defects, Congenital; Humans; Infant; Male; Phosphodiesterase Inhibitors; Piperazines; Pulmonary Circulation; Purines; Sildenafil Citrate; Sulfones; Vascular Diseases; Vasodilator Agents

Topics: Adult; Aged; Arteriosclerosis; Humans; Impotence, Vasculogenic; Male; Middle Aged; Piperazines; Purines; Sildenafil Citrate; Sulfones; Vascular Diseases; Vasodilator Agents

Sildenafil is frequently the first-line treatment for post-radical retropubic prostatectomy (RRP) erectile dysfunction (ED) with maximum treatment satisfaction rates of 43%-80%. The etiology of erectile dysfunction after RRP has been attributed to psychogenic, vascular, veno- occlusive or nerve injury causes. The purpose of this study was to gain insight into the penile duplex Doppler arterial parameters in men with ED after RRP who failed sildenafil. The purpose was to assess whether sildenafil failure after RRP is associated with underlying corporal arterial disease. A total of 174 consecutive men presenting with sildenafil refractory ED after nerve-sparing RRP underwent color duplex penile Doppler evaluation with vasoactive injection. Mean age was 59.6 y and mean time from surgery was 11.6 months. Some 81% (141/174) of the men had no pre-operative ED (PED). Significant differences in penile duplex Doppler parameters for arterial disease were seen between men with and without PED. In men without PED, 19% (27/141) manifested arterial insufficiency. However, in men with PED, 50% (16/33) demonstrated arterial disease. Nerve sparing status did not affect the presence of arterial disease. Sildenafil refractory erectile dysfunction after RRP in men without PED is not predominantly associated with penile Doppler parameters consistent with arterial insufficiency.

Topics: Aged; Arteries; Erectile Dysfunction; Humans; Male; Middle Aged; Penis; Phosphodiesterase Inhibitors; Piperazines; Prostatectomy; Purines; Sildenafil Citrate; Sulfones; Treatment Failure; Ultrasonography, Doppler, Duplex; Vascular Diseases

Erectile dysfunction (ED) has frequently been associated with Peyronie's Disease (PD) and may further compromise coitus. This is a retrospective analysis of ED in patients with PD since the release of sildenafil citrate (SC) focusing specifically on our patients' responses to SC. One-hundred seventy six patients with PD were evaluated between April 1998 and May 2001. All patients received a complete medical and sexual history, physical exam, penile duplex ultrasound (PDU, with 30-90 mg of papaverine) to assess penile vascular integrity, plaque dimensions, and erect penile deformity. Based on these findings, appropriate treatment options were offered for their PD and their ED including SC, which was offered to 73 men. Patient response to SC was specifically assessed during patient office interview and via a mailed EDITS (Erectile Dysfunction Inventory of Treatment Satisfaction) questionnaire. Seventy (39.8%) and 104 (59.1%) patients complained of decreased erectile capacity (ie rigidity) occurring before and after the onset of PD, respectively. Only two patients reported no change of erectile capacity. In all, 103 (58.5%) patients complained of significant reduction in sexual function due to diminished rigidity and sought treatment for their ED. Of the ED treatment options available, 73 (70.9%) patients were given a prescription for SC. Forty-eight (75.0%) patients returned the EDITS questionnaire while four of 73 (5.5%) patients did not fill their prescription and five of 73 (6.8%) did not engage in sexual activity following an initial trial of SC due to side effects (flushing, headaches). Based upon the EDITS response, 34 of 48 (70.8%) patients reported that they were either very satisfied or somewhat satisfied, five of 48 (10.4%) patients were neither satisfied nor dissatisfied, and nine of 48 (18.8%) patients were somewhat dissatisfied or very dissatisfied with the effectiveness of SC in enhancing their erectile response. No patient reported worsening of PD deformity or an increase in penile pain. The 30 patients who were not prescribed SC chose the following options to enhance rigidity: eight (7.8%) underwent prosthesis placement, four (3.9%) opted for vacuum constriction device (VCD), four (3.9%) chose intracorporal injections, and 14 (13.6%) used no adjunctive therapy. Erectile dysfunction is a problem associated with PD and all typical treatment options are acceptable. However, to our knowledge, there is no published study reviewing the efficacy of

Topics: Arteries; Erectile Dysfunction; Humans; Male; Patient Satisfaction; Penile Induration; Penis; Phosphodiesterase Inhibitors; Piperazines; Purines; Retrospective Studies; Sildenafil Citrate; Sulfones; Surveys and Questionnaires; Treatment Outcome; Vascular Diseases