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 (Viagra) (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 theSildenafil Citrate (Viagra) 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 (Viagra) promotes myocardial protection in infant rabbits as evidenced by postischemic preservation and elevation in LVCO and aortic VTI and reduction in infarct size

Sildenafil induces retinal vasodilatation in healthy subjects.

BACKGROUND: The cardiovascular effects of Sildenafil Citrate (Viagra), a selective inhibitor of phosphodiesterase type 5 (PDE5), have been extensively studied. However, its effect on human retinal arteries and veins has not yet been investigated. The effect of a single dose administration ofSildenafil Citrate (Viagra) on the retinal vessel diameters of healthy subjects was evaluated. METHODS:Sildenafil Citrate (Viagra) 50 mg was administered to 10 healthy subjects (male:female = 4:6; mean age 31 (SD 6) years). The diameters of retinal arteries and veins were measured by means of a retinal vessel analyser (RVA) immediately before and at 30, 60, 90, and 120 minutes afterSildenafil Citrate (Viagra) uptake. Blood pressure, heart rate, and intraocular pressure were monitored in parallel. RESULTS: A significant increase of 5.8% (p<0.001) in both retinal arterial and venous diameters was found 30 minutes afterSildenafil Citrate (Viagra) uptake. The diameters returned to baseline after 120 minutes. A mild systemic hypotensive response was seen. Changes in heart rate and intraocular pressure were not observed. CONCLUSION:Sildenafil Citrate (Viagra) causes a significant dilatation of retinal arteries and veins in healthy subjects. A possible role for PDE5 in the regulation of retinal blood flow is implicated

Effect of Sildenafil Citrate (Viagra) on penile erection of rhesus macaques.

AIM: To examine the effect of Sildenafil Citrate (Viagra) on penile erection of male rhesus macaque. METHODS: Twenty Macaca mulatta were divided into theSildenafil Citrate (Viagra) treated and the control groups of 10 animals each. The penile size, the corpus cavernosal electromyogram (EMG) and the intra-corpus cavernosal pressure (ICP) were determined. RESULTS: The diameter of penis and the ICP were significantly increased and the corpus cavernosal EMG significantly reduced in theSildenafil Citrate (Viagra) group. CONCLUSION: Sildenafil Citrate (Viagra) increases the penile size and ICP and reduces the corpus cavernosal EMG in male rhesus macaque

Marked improvement withSildenafil Citrate (Viagra) in a patient with primary pulmonary hypertension unresponsive to epoprostenol.

We report a 48-year-old woman with right heart failure due to primary pulmonary hypertension. Continuous infusion of epoprostenol (prostaglandin I2) for 1.5 years failed to control her condition, but she was later successfully treated with additionalSildenafil Citrate (Viagra) for a few months. Her mean pulmonary artery pressure was originally 57 mmHg, increased to 62 mmHg with epoprostenol, and decreased to 45 mmHg with sildenafil. AdditionalSildenafil Citrate (Viagra) may be an effective and life-saving agent in patients with primary pulmonary hypertension who show a poor response to epoprostenol, which is considered to be very powerful medical treatment for the disease

The effect of age onSildenafil Citrate (Viagra) biotransformation in rat and mouse liver microsomes.

Sildenafil [SIL (Viagra); Pfizer, New York, NY] is a widely prescribed agent for Erectile Dysfunction in men older than 65 years. The present study evaluated experimental models to assess age-dependent changes in SIL biotransformation using hepatic microsomes from male rats and mice ranging from 6 weeks to 26 months of age. The role of specific isoforms in the conversion of SIL to its primary circulating metabolite, UK-103,320 (piperazine N-desmethyl sildenafil) in the mouse was also investigated using immunoinhibitory antibodies. Although CYP2C11 largely mediated UK-103,320 formation in the rat, UK-103,320 formation was principally inhibited by a CYP3A antibody in the mouse. An age-related decrement in metabolite formation rate was observed for both species, although this effect was more pronounced in the old rats (reduced to 7% of young) than in the old mice (reduced to 51% of young). CYP2C expression was assessed by Western blot analysis in rat and mouse livers. Age-related differences in hepatic CYP3A expression in the mouse were also compared with metabolite formation rates in the mouse model. Decrements with age in CYP2C and -3A expression in the aging rodents paralleled the decrements in SIL biotransformation, suggesting that age-related differences in SIL metabolic rate may, in part, reflect differences in expression. Although the role of specific CYP enzymes and the clearance values for this reaction may differ among species, age-related changes in these rodent models are consistent with the reduced clearance of SIL observed in human studies

Sildenafil: a new oral therapy for Erectile Dysfunction.

Sildenafil Citrate (Viagra) is a relatively selective 5-phosphodiesterase (PDE) inhibitor. It is the first oral medication approved for the treatment of Erectile Dysfunction (ED). The neuronal release of NO which binds to the heme-containing region of guanylate cyclase increases levels of cGMP. This leads to a cascade of reaction which results in corporal smooth muscle relaxation and penile erection.Sildenafil Citrate (Viagra) causes an erection by inhibiting PDE5, which in turn causes an increase in the intracellular levels of cGMP.Sildenafil Citrate (Viagra) is well absorbed after a single oral administration with a t(1/2) of approximately 4 h. The mode of onset varies from 0.5-4 h. The drug has been used in millions of men since first approved by the U.S. FDA 1 year ago and has revolutionized the approach to, and therapy of, Erectile Dysfunction. (c) 1999 Prous Science. All rights reserved

Demand, appropriateness and prescribing of 'lifestyle drugs': a consultation survey in general practice.

BACKGROUND: The simultaneous launch of orlistat andSildenafil Citrate (Viagra) in 1998 provoked much media attention, particularly around the role of lifestyle drugs and their potential costs if controls were not established. Fears were also expressed that primary care would be overwhelmed by demand, and little information was available about the attitude of GPs to their new role as prescribers of lifestlye drugs. Partly in response to these concerns, tight prescribing guidelines and licensed indications, forSildenafil Citrate (Viagra) and orlistat, respectively, were issued. OBJECTIVE: Our aim was to describe levels of demand for orlistat andSildenafil Citrate (Viagra) in general practice, whether this demand was translated into a prescription, adherence to prescribing guidelines/licensed indications and the GP perception of appropriateness of an NHS prescription for either of these drugs. METHOD: We carried out an observational study in primary care conducted over a 6-week period during 1999. Twenty-seven GPs were recruited, each from a different practice. All GP consultations were recorded for the study period and the GP completed a structured questionnaire each timeSildenafil Citrate (Viagra) or orlistat were discussed in a consultation. RESULTS:Sildenafil Citrate (Viagra) was discussed in 0.5% (68/13 394) of consultations and orlistat in 0.3% (42/13 394). GPs thought that a corresponding NHS prescription would be highly appropriate in 57 and 74% of cases, respectively, although for both lifestyle drugs, nearly 20% of GPs thought such prescriptions were inappropriate. An NHS prescription was issued in 43% of consultations in whichSildenafil Citrate (Viagra) had been discussed and 33% in which orlistat had been discussed. Five out of 29 NHSSildenafil Citrate (Viagra) prescriptions were issued to patients failing to fulfil the requirements of prescribing guidelines; similarly, one out of 14 orlistat prescriptions fell outside licensed indications. There were four examples of NHS prescriptions forSildenafil Citrate (Viagra) which were given even when the GP thought the drug to be inappropriate, whereas orlistat was never given when the GP thought it inappropriate. CONCLUSIONS: Levels of demand for the two lifestyle drugs,Sildenafil Citrate (Viagra) and orlistat, were modest when compared with earlier media predictions. Neither was there evidence that GP was pitted against patient in their negotiation concerning a lifestyle drug NHS prescription since most GPs agreed with their patients that such a prescription was appropriate. Prescribing guidelines and licensed indications were generally adhered to, but the modest level of demand raises questions about expanding the guidelines 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)