Coronary artery flow reserve in diabetics with Erectile Dysfunction using sildenafil.

BACKGROUND: Diabetics with Erectile Dysfunction have a high prevalence of microvascular disturbance of the coronary circuit as measured by coronary flow reserve (CFR). PURPOSE: We aimed to evaluate the effects of the phosphodiesterase 5 inhibitorSildenafil Citrate (Viagra) on CFR in diabetics with Erectile Dysfunction. METHODS: Diabetics seeking diabetes refinement therapy were screened for vascular or neurogenic Erectile Dysfunction which was confirmed in 43 patients. No ischemic ECG changes were found in any of the ECG stress tests at the 100 W level. Cardiologic examinations raised suspicion of coronary artery disease in 16 patients; coronary angiography confirmed severe coronary artery lesions in 12, who were excluded from further analysis. CFR measurements were not possible in 10 participants. The 21 diabetics eligible for CFR measurements aged 60 years (50-69) had known diabetes for 11 years (3-30) and a BMI of 27 kg/m2 (24-36). CFR of the left anterior descending artery was assessed at baseline and 1 hour after 50 mg sildenafil, using transthoracic Doppler echocardiography. RESULTS: Baseline CFR was at the lower level of the normal range (median 245%, range 210 - 490%). AfterSildenafil Citrate (Viagra) administration, CFR decreased insignificantly (DeltaCFR -10%, p = 0.3). Patients with a BMI > 25 kg/m2 and left ventricular hypertrophy exhibited the highest reduction of CFR after sildenafil. No decrease of CFR below 200 % was observed. Systemic blood pressure dropped from 130/80 mmHg to 120/72 mmHg (p < 0.002). CONCLUSIONS: Diabetics with Erectile Dysfunction exhibit a CFR in the lower normal range indicating severe microvascular disturbance.Sildenafil Citrate (Viagra) did not alter CFR in those patients. A high prevalence of severe coronary macroangiopathy was identified in asymptomatic diabetic patients screened for contraindications forSildenafil Citrate (Viagra)

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 plusSildenafil Citrate (Viagra) 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 plusSildenafil Citrate (Viagra) 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 theSildenafil Citrate (Viagra) 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 toSildenafil Citrate (Viagra)

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, a phosphodiesterase-5 inhibitor, delays gastric emptying and gastrointestinal transit of liquid in awake rats.

We studied the effect ofSildenafil Citrate (Viagra) on gastric emptying (GE) and gastrointestinal (GI) transit in awake rats. After cervical vessel cannulation and 24 hr of fasting, the animals received an intravenous (IV) injection ofSildenafil Citrate (Viagra) (4 mg/kg) or vehicle. Next they were gavage fed (1.5 ml) with a test meal (phenol red in 5% glucose solution, 0.5 mg/ml) and sacrificed 10, 20, or 30 min later. Experimental and control subsets consisted of 5-10 rats. Gastric and proximal, medial, and distal small intestine dye retentions (GDR and IDR, respectively) were obtained by spectrophotometry. Data were compared by ANOVA and Student-Newman-Keuls test. In sildenafil-treated animals, GDR increased (P < 0.05) by 20.3%, 46.9%, and 55,5% while medial IDR decreased (P < 0.05) by 35.1%, 43.4%, and 41.6%, respectively, at 10, 20, and 30-min intervals. Proximal and distal IDR values did not change in sildenafil-treated animals. Mean arterial pressure (MAP) decreased 25% (P < 0.05) right afterSildenafil Citrate (Viagra) administration but normalized afterwards while in controls MAP remained unchanged. In conclusion,Sildenafil Citrate (Viagra) delays GE and GI transit of a liquid meal while transiently decreases MAP in awake rats

Management of Erectile Dysfunction by combination therapy with testosterone andSildenafil Citrate (Viagra) in recipients of high-dose therapy for haematological malignancies.

Erectile Dysfunction (ED) is a well recognised complication of bone marrow transplantation, which affects quality of life in adult patients. Although the major contributory factors include hypogonadism and psychogenic factors, the best treatment still remains to be established due to the complex aetiopathology of the condition. Here, we report our preliminary results in eight patients treated with testosterone replacement therapy and sildenafil. We studied eight male recipients of BMT aged 22-58 years, presenting with clinical features of hypogonadism, ED, diminished libido and ejaculatory disorders. ED was assessed clinically and by colour flow Doppler studies of the cavernosal vessels. Testicular function was assessed by testicular volume, FSH, LH and testosterone (T) measurements. Erectile performance, libido and ejaculatory function were determined by a structured interview. Patients had severe primary hypogonadism as evidenced by low mean testicular volume, elevated gonadotrophins and low normal mean testosterone levels compared with controls. All had Leydig cell insufficiency (LCI) with or without frank serum testosterone insufficiency. All except one had cavernosal arterial insufficiency. All patients received intramuscular injections of testosterone cypionate (250 mg 4 weekly) for 6 months and 50-100 mg ofSildenafil Citrate (Viagra) orally, one to two times per week. All patients responded favourably as substantiated from the NIH consensus criteria. Our preliminary results suggest that this combined therapy is a safe and effective therapeutic approach in recipients of high-dose therapy presenting with ED after transplant

Prehospital consideration of sildenafil-nitrate interactions.

OBJECTIVE: To determine whether paramedics and on-line physicians screen patients for use of Sildenafil Citrate (Viagra) prior to prehospital administration of nitrates. METHODS: A prospective, observational study was performed over a one-month period in three EMS systems. Consecutive radio communications between on-line physicians and paramedics concerning male patients with cardiac complaints were monitored. Investigators observed the frequency with which on-line physicians screened forSildenafil Citrate (Viagra) use prior to ordering nitrates. After observation of the radio communications was completed, a written survey was distributed to all paramedics in the three EMS systems. RESULTS: Seventy-six physician-paramedic interactions were monitored. Nitrates were ordered by on-line physicians in 56 cases. No paramedic reportedSildenafil Citrate (Viagra) use/nonuse, and no on-line physician inquired about the patient's potential use of the drug. Only half of the surveyed paramedics reported that they routinely screen forSildenafil Citrate (Viagra) use, and approximately a fourth reported that its use would not alter their management of chest pain patients. CONCLUSION: In this study, on-line physicians in three EMS settings did not screen forSildenafil Citrate (Viagra) use prior to ordering nitrates. While some paramedics do screen forSildenafil Citrate (Viagra) use, practice patterns among paramedics in these three systems were inconsistent

Effects ofSildenafil Citrate (Viagra) on myocardial infarct size, microvascular function, and acute ischemic left ventricular dilation.

OBJECTIVE: Adverse cardiac events in patients treated with the phosphodiesterase-5 inhibitorSildenafil Citrate (Viagra) for Erectile Dysfunction raised concerns about its safety in ischemic heart disease. METHODS: In anesthetized open-chest rabbits, receiving 1.45 mg/kgSildenafil Citrate (Viagra) intravenously or saline 30 min prior to ischemia (n=12, each), infarct size (IS, triphenyltetrazolium), the area of no-reflow (ANR, thioflavin S) (% of the risk area, RA, blue dye), and regional myocardial blood flow (RMBF, radioactive microspheres) were measured after 30 min of coronary occlusion and 180 min of reperfusion. Left ventricular hemodynamics and dimensions (echocardiography) were determined in a separate series of animals (n=5, each). RESULTS:Sildenafil Citrate (Viagra) significantly lowered arterial blood pressure before occlusion (-17 to -19 mmHg over 30 min), but during ischemia and reperfusion hemodynamics were comparable to controls. IS in treated animals (51+/-4%) did not significantly differ from control animals (47+/-4%). No major arrhythmias or lengthening of QT/QTc occurred. WhileSildenafil Citrate (Viagra) slightly increased RMBF and significantly reduced specific vascular resistance in the RA during reperfusion (51+/-7 versus 73+/-10 mmHg g min/ml, P<0.05), the ANR (46+/-3%) was similar to control animals (44+/-4%).Sildenafil Citrate (Viagra) reduced left ventricular dP/dt(max) (P<0.05) and dP/dt(min) (P<0.01) in non-ischemic conditions, and slightly during ischemia, along with a pronounced decrease in ischemic left ventricular end-diastolic pressure (9+/-2 versus 15+/-2 mmHg after saline, P<0.05), but did not attenuate acute ischemic left ventricular dilation. CONCLUSIONS:Sildenafil Citrate (Viagra) reduced cardiac pre- and afterload, and parameters of left ventricular contractility. Myocardial necrosis and microvascular dysfunction were neither exacerbated nor attenuated

Identification system forSildenafil Citrate (Viagra) in health foods

A substantially available identification system forSildenafil Citrate (Viagra) in health foods was established using 3 different analytical methods; i.e. TLC, preparative TLC/MS and HPLC/photo-diode array.Sildenafil Citrate (Viagra) in health foods was extracted with ethyl acetate under alkaline conditions as sample solutions for TLC and preparative TLC, and also extracted with 50% methanol and then diluted with solution of HPLC mobile phase for HPLC. The sample solution for TLC was applied to Silica gel 60 F254 plates with chloroform/methanol/28% ammonia (90:1:5, under layer) as mobile phase. Spots were located under UV radiation at 254 nm and 366 nm, and spraying dragendorff reagent. The conditions for preparative TLC were the same as these of TLC method, and samples abtained from preparative TLC were determined by MS with APCI interface, under both positive and negative modes. The HPLC analysis was carried out on a column of Cosmosil 5C18-AR (4.6 mm x 150 mm, 5 microns) with 0.05 mol/l phosphate buffer pH 3.0/acetonitrile(73:27) as mobile phase and the eluate was monitored by a photo-diode array detector. The quantitative analysis was available, when the peak of this sample on HPLC was detected at 290 nm. When this system was applied to commercial health foods,Sildenafil Citrate (Viagra) was identified and their contents were 25 mg-45 mg/tablet or bottle. These contents nearly correspond to that in Viagra, 25 mg, 50 mg/tablet. Therefore, there is a fear of side effects for Sildenafil, when it is taken as health foods