Sildenafil Group Research Articles

Sildenafil citrate adjuvant treatment in women with polycystic ovary syndrome following clomiphene failure: A randomized controlled trial

Objective: The widespread classic PCOS treatment algorithm, consisting of 6-12 cycles of clomiphene followed by shifting to gonadotropins in case of failure to conceive, doesn’t really address the cause of failure to conceive despite documented ovulation. Sildenafil citrate improves uterine blood flow, enhances endometrial development and modulates endometrial receptivity. Hence, this study monitored the ovarian response, endometrial development and subendometrial Doppler changes in PCOS women with previous clomiphene citrate failure following the use of adjuvant sildenafil citrate instead of shifting to gonadotropins. Patients and Methods: A double-blinded randomized controlled trial was conducted in Ain-Shams University Women’s Hospital on 850 PCOS women with clomiphene failure. Those were randomized to clomiphene therapy, either with adjuvant placebo or sildenafil citrate (25 mg orally 6 hourly), starting from the 6th day till the end of the cycle.Folliculometry, every other day, started on the 10th day of the cycle. When ≥1 follicle reached a size ≥18mm, transvaginal ultrasound assessment of the endometrium and uterine/subendometrial Doppler was done. The resulting pregnancy rates were recorded. Results: The sildenafil group developed higher endometrial thickness (10.6±1.3 versus 9.4±1.5; p<0.001), a higher percentage of women with trilaminar endometrium (78.35% versus 59.76%; p<0.001) was found while the lower percentage was found with subendometrial and uterine artery Doppler indices (p<0.001 for all). It also developed higher pregnancy rates (43.7% versus 34.5%, p=0.006; NNT=10.8, 95% CI: 6.36 – 37.84).Conclusion: Sildenafil adjuvant therapy significantly increased pregnancy rates, improved endometrial development in terms of endometrial thickness and pattern as well as uterine and subendometrial blood flow.

The Effect of Phosphodiesterase Type 5 Inhibitors on the Development of Retinopathy of Prematurity in Imam Khomeini Hospital's, Ahvaz, Iran Preterm Infants: A Randomized Clinical Trial

Background: Retinopathy of prematurity (ROP) affects premature infants, and it is characterized by the development of vascular proliferation due to hyperoxia, down regulation of Vascular endothelial growth factor(VEGF) and death of endothelial cells. We hypothesized that inhibition of Phosphodiesterase 5 enzyme suppresses retinal vasoconstriction and prevent ROP.&#x0D; Study Design: 109 newborns with respiratory distress syndrome treated with oxygen with early gestational age (GA) ≤30 weeks and birth weight (BW) ≤1500 g were randomized into two groups, 52 patients in sildenafil and 50 patients in placebo group were studied, Group sildenafil (as case group) and placebo Group (as control group), sildenafil was administered via nasogastric tube. Occurrence of ROP phase 1 as primary outcome and stage 2-5 ROP, duration of mechanical ventilation, oxygen therapy and duration of hospitalization as secondary outcomes were assessed.&#x0D; Results: There was no differences between the two group in demographic characteristics. ROP phase 1 was seen in 11(22%) and 7(14%) of placebo and interventional group, respectively. Stage 3 ROP was not seen in any of the patients.&#x0D; Conclusion: Sildenafil therapy did not affect ROP development in premature infants treated with oxygen. May be due to our exclusion criteria (BW less than 1000g) and this fact that there is a high incidence of ROP in extremely low birth weight neonates, we didn’t find any significant difference. More studies with larger population and expanded criteria are needed to find the effect of sildenafil on ROP.

The effect of sildenafil on pleural and peritoneal effusions after the TCPC operation.

We evaluated whether the administration of sildenafil in children undergoing the TCPC operation shortened the interval from the operation to the removal of the pleural and peritoneal drains. We retrospectively reviewed the data of 122 patients who had undergone the TCPC operation between 2004 and 2014. Patients were divided into two groups on the basis of their treatments. Sildenafil was orally administered pre-operatively in the morning of the procedure or within 24hours after the TCPC operation to the sildenafil group (n=48), which was compared to a control group (n=60). Fourteen patients were excluded from the study. The primary outcome measure was the time from the operation to the removal of the drains. The study groups had similar demographics. The median [interquartile range] time for the removal of drains (sildenafil group 11 [8-19] vs control group 11 [7-16] d, P=.532) was comparable between the groups. The median [interquartile range] fluid balance on the first post-operative day was significantly higher (P=.001) in the sildenafil group compared with controls (47 [12-103] vs 7 [-6-67] mLkg-1 ). The first post-operative day fluid balance was a significant predictor for a prolonged need for drains in the multivariate analysis. Sildenafil administration, pre-operatively or within 24hours after the TCPC operation, did not reduce the required time for pleural and peritoneal drains but was associated with a significantly higher positive fluid balance.

Efficacy and tolerability of sildenafil/l-arginine combination relative to sildenafil alone in patients with organic erectile dysfunction.

Erectile dysfunction is defined as inability to achieve or maintain penile erection sufficient for sexual satisfaction. It is a serious problem that increases by age. The physiology of penile erection depends mainly on nitric oxide release. Compare the efficacy and safety of oral sildenafil 50mg alone or in combination with l-arginine 3g/day orally on the treatment of erectile dysfunction. Randomized controlled study with two parallel groups of erectile dysfunction patients; One group received sildenafil 50mg every other day, while the other group received a combination of sildenafil (every other day)/l-arginine on a daily base. Efficacy was assessed using International Index of Erectile Function-5 score at the baseline and after 8weeks. Side effects were evaluated across the two groups. The mean age was 56.3±5 and 56.2±4.4years in sildenafil and combination groups, respectively. International Index of Erectile Function-5 score was comparable between the two groups at the baseline (p value 0.44). International Index of Erectile Function-5 score was improved from 15.3±2.5 at baseline to 19.2±2.3 after treatment, and this was statistically significant with p value <0.0001. The score was slightly better in combination group in which the average International Index of Erectile Function-5 score was (19.8±2.2) vs. (18.5±2.3) in sildenafil group with p value 0.05. Side effects were more or less the same between the two groups except for gastritis which was more common on combination group. Adding l-arginine to sildenafil demonstrated more efficacy than sildenafil alone for treatment of erectile dysfunction patients.

Can a woman with sexual dysfunction take sildenafil citrate?

Background: Sexual dysfunction refers to a problem that occurs during the sexual response cycle that prevents the individual from experiencing satisfaction from sexual activity. The assessment of sexual function in women is frequently confounded by many factors, including depressed mood and other comorbid medical and psychiatric disorders. Sildenafil is selective type 5 phosphodiesterase (PDE5) inhibitors, taken orally and effective for men with erectile dysfunction. Previous studies suggested that sildenafil, which acts by inhibiting cyclic GMP specific PDE5 may improve the sexual health of women affected by sexual difficulties such as arousal disorders and may indirectly improve other aspects of sexual life. Sildenafil was effective and well-tolerated in postmenopausal women with sexual arousal disorder without concomitant hypoactive sexual desire disorder or contributory emotional relationship or historical abuse issues.Objective: This study aims to evaluate the effect of sildenafil citrate on female sexual dysfunction.Patients and Methods: The study was conducted in Dermatology, Venereology, and Andrology Department, Faculty of Medicine, Zagazig University Hospitals during the period from April 2017 to August 2018. Fifty-two married female patients were included in this study. Patients were divided into two groups. Group 1 contains twenty-six patients took 50mg sildenafil on-demand and group 2 contains twenty-six patients took a placebo.Results: There were no significant differences between the studied groups regarding the demographic data and FSFI. There were significant differences between pre and post-treatment of sexual dysfunction regarding group І. There were no significant differences in post-treatment results between the two studied groups as regard sexual dysfunction except in orgasm.Conclusion: Sildenafil citrate may be effective in women who could not achieve orgasm

388 A multicenter study on the use of Sildenafil for lymphatic malformation in children

Lymphatic malformations (LMs) are progressive, congenital vascular anomalies that arise due to developmental dysplasia of the lymphatic network in utero. There is no FDA approved treatment. It has been hypothesized that the therapeutic effects of sildenafil may result from simple smooth muscle relaxation, which facilitate lymphatic drainage leading to decompression of the malformation. To date, this double-blind, placebo controlled multicenter study has enrolled 15 patients 6 mo to 10 yr of age with LM over 3 cm in diameter. Participants were randomized at 2:1 ratio, that is two sildenafil treated subjects for each placebo treated subject. The subjects randomized to placebo will have the option to begin a 20-wk open label treatment with sildenafil. The subjects were evaluated in clinic at wks 4, 12, 20, 32. Telephone interviews were conducted at wks 2, 8 and 16. Laboratory and MRI evaluations were obtained at baseline and wk 20. Volume changes from MRI evaluation were analyzed. Physician and parent’s clinical assessments of LM were documented. There are no serious adverse events reported. Percentage of volumetric change trend to decrease in sildenafil group, in contrast to placebo group trending to increase (-0.47 v.s. 5.88). Statistical significance was not achieved due to small cohort size. Thus, our interim analysis has demonstrated safety of sildenafil treatment in young children with LM. Although not statistically significant, there appear to be some benefit in softening and reducing distortion of LM . Intra-object analysis showed more volume reduction when patients transition from placebo to sildenafil treatment.

Use of Phosphodiesterase Inhibition During Ex-Vivo Lung Perfusion of Donor Lungs Unsuitable for Transplantation

Purpose Primary Graft Dysfunction after lung transplantation is characterised by inflammatory cascade activation, vascular leak and pulmonary oedema. Nitric oxide signalling plays a critical role in pulmonary vascular homeostasis. Reduced cyclic guanosine monophosphate (cGMP) following ex-vivo lung perfusion (EVLP) is associated with increased microvascular permeability. Phosphodiesterase-5 inhibitors e.g. Sildenafil prevent cGMP breakdown causing pulmonary vasodilation and reduced pulmonary vascular resistance (PVR). We investigated the effects of Sildenafil during EVLP on physiology, inflammatory status and endothelial activation markers. Methods Five human, clinically unused donor lungs, underwent acellular EVLP with 40% predicted cardiac output and a closed left atrium. Following 30 minutes of stable EVLP, a 10mg Sildenafil (Revatio; Pfizer) bolus was administered. Haemodynamic data was continuously monitored and perfusate sampled at intervals and evaluated via a MSD pro-inflammatory panel.Physiological data was compared using ANOVA method. Inflammatory protein concentrations were compared with DEVELOP-UK historical control data and analysed by multiple unpaired t-tests. Results Following Sildenafil administration, rapid development of alveolar oedema was observed. No measured effects on pulmonary haemodynamics including flow, PAP, PVR and oxygenation were seen. The overall trends for the pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) were similar in both groups. Significance was observed at the final 120-minute time-point; with higher levels of IL-8 and TNF-α following Sildenafil. The treatment group had significantly decreased expression of soluble tight junctional proteins (VE-cadherin, thrombomodulin and VWF) compared to the control group. Conclusion Sildenafil didn't improve pulmonary physiology as expected and appeared to promote the development of alveolar oedema. While the mechanism for this remains unclear, we observed significantly lower concentrations of the endothelial damage markers in the Sildenafil group. This difference may be confounded by the control group being a historical cohort which used a different EVLP protocol, limiting comparison. We conclude that Sildenafil failed to have the hypothesised therapeutic effects and is detrimental to lungs undergoing EVLP.

Screening of illegal sexual enhancement supplements and counterfeit drugs sold in the online and offline markets between 2014 and 2017

The worldwide spread of illegal sexual enhancement products is posing a threat to public health. The aim of this study was to investigate illegal products claiming to be effective in improving sexual performance through the online or offline markets between 2014 and 2017; these products include foods, dietary supplements, counterfeit drugs, and herbal medicines. These samples were analysed by liquid chromatography-tandem mass spectrometry (LC–MS/MS) for the presence of 80 PDE-5 inhibitors (PDE-5i) and analogues. The developed method was validated as follows: LODs and LOQs spiked in solid- and liquid-type negative samples (0.03–3.33 ng/mL and 0.08–10.00 ng/mL), linearities (R2 > 0.997), recoveries spiked negative samples (82.2–109.3 %), accuracies (81.6–118.9 %), precisions (≥ 6.5%, RSD) of intra-day and inter-day, and stability (≥10.0%, RSD). Out of 362 measured samples, 145 were adulterated samples mostly detected in food (51%). Sildenafil group (50%) was frequently observed, followed by tadalafil group (41%). Although sildenafil and tadalafil were mainly detected in adulterated samples, their analogues were also found. In particular, new analogues have appeared steadily on illicit erectile dysfunction (ED) products even after they were first discovered. The concentration of detected samples ranged from 0.1 to 826.0 mg/g, and sildenafil of them contained a considerable amount in illicit ED products in 2014, posing a potential toxicology risk of public health. The testing method is fast and reliable making it suitable for both routine screening and up-to-date quantitative analysis of PDE-5i and their analogues in suspicious foods, dietary supplements, and counterfeit drugs.

Effect of sildenafil on stable chronic heart failure: a prospective randomized-controlled clinical trial

Background Patients with systolic heart failure (HF) who develop secondary pulmonary hypertension have reduced exercise capacity and increased mortality compared with HF patients without pulmonary hypertension. A defective nitric oxide signaling is involved in left ventricular (LV) diastolic abnormalities and remodeling. Phosphodiesterase type 5 inhibition, by blocking degradation of nitric oxide second-messenger cyclic guanosine monophosphate, might be beneficial. Aim of the study In our study, we tested the effects of phosphodiesterase type 5 inhibition (sildenafil) on LV ejection fraction, diastolic function, pulmonary artery pressure, and clinical status. Patients, methods, and results One hundred HF patients (New York Heart Association classes II–IV) were assigned randomly to placebo or sildenafil (50 mg three times per day) for 6 months, with assessment at the first and 6 months of LV ejection fraction, diastolic function, pulmonary artery systolic pressure, and exercise performance (using 6 min walk test). The two groups studied were similar in terms of age, sex distribution, etiology of cardiomyopathy, the prevalence of chronic atrial fibrillation, LVEDD, LA dimensions, and pulmonary artery pressure as well as drug therapy is given to each group all through the study period (P > 0.05). After 1 month of therapy, there was a significant increase in LV ejection fraction and a decrease in pulmonary artery systolic pressure in the sildenafil group (P 0.05). Doppler-derived variables of LV diastolic function improved significantly in the sildenafil group (P 0.05). Over 6 months of therapy and follow-up, LV ejection fraction increased from 31.5 ± 5.4 to 36.4 ± 3.5 and the difference was not significant between the two groups (P > 0.05), whereas in the sildenafil group, ejection fraction % increased significantly from 30.6 ± 4.5% at baseline to 45.6 ± 5.4% (P 0.05), whereas in the sildenafil group, it decreased significantly from 48.3 ± 17.7 to 28.4 ± 6.4 mmHg (P Conclusion In patients with HF, long-term use of sildenafil was well tolerated. This therapeutic regimen (50 mg three times per day) promoted a sustained significant improvement in LV systolic and diastolic function properties in comparison with placebo.

Comparison of Endometrial Thickness with Concomitant Administration of Sildenafil Citrate and Ethinyl Estradiol vs Ethinyl Estradiol Alone for Frozen Embryo Transfer

Introduction: Infertility is one of the common medical issues in today's world. One of the common causes of infertility is the lack of implantation of the embryo. Aim: To compare the effect of Ethinyl Estradiol (E2) alone on Endometrial Thickness (ET) with that of sildenafil citrate and E2 combination. Materials and Methods: In this clinical trial, 70 infertile women undergoing treatment with Assisted Reproductive Techniques (ARTs) were randomly divided into two groups of 35 each. One group received E2 and vaginal sildenafil and the other E2 alone. On the seventh day of the cycle and, if necessary, until ET reached 8 mm, ET in both groups was measured by transvaginal ultrasound. After the embryo transfer, Beta-Human Chorionic Gonadotropin (BHCG) was performed in both groups. The measured thickness of uterus and BHCG were recorded in the checklist for both groups. Data were analysed by SPSS and p<0.05 was considered significant. Results: The mean duration (in days) to reach an 8 mm ET in infertile women in the E2+sildenafil group (13.59 +/- 3.07) was lower than that in the E2 group (14.88 +/- 4.78), yet insignificant (p=0.21). Although the mean dose (mg) of E2 and duration (day) to reach an 8 mm ET in the E2+ sildenafil group was lower than those in the E2 group, significance (p) levels were 0.02 and 0.21, respectively. Conclusion: In infertile women undergoing ARTs, co-administration of sildenafil citrate and E2 increased ET relatively and reduced the dose of E2 and the duration of its administration.

The effects of specific and non-specific phosphodiesterase inhibitors and N-acetylcysteine on oxidative stress and remote organ injury in two-hit trauma model.

Sepsis is a systemic inflammatory response to infection and is one of the leading causes of morbidity and mortality. The second hit after trauma causes increased inflammatory response and multiple organ failure (MOF). The infection which develops after burn injury is a suitable model for a two-hit trauma study. Sepsis causes the release of biochemical mediators, such as Free Oxygen Radicals (FORs), which may lead to lipid peroxidation, which may play a key role in multiple organ failure. In this study, we aimed to investigate the effects of phosphodiesterase (PDE) inhibitors (sildenafil, milrinone, pentoxifylline) and N-acetylcysteine (NAS) on oxidative stress and organ damage in two-hit models. In this experimental study, peritonitis was created by cecal ligation and puncture (CLP) method in 40 rats, 72 hours after creating a 30% scalding injury. Rats were divided into five groups of eight rats each as follows: Group I: No treatment; Group II: 10/mg/kg/day dosage of intraperitoneal (i.p) sildenafil treatment was applied for 72 hours after CLP; Group III: 1/mg/kg/day dosage of i.p milrinone treatment was applied for 72 hours after CLP; Group IV: 150/mg/kg/day dosage of i.p NAS treatment was applied for 72 hours after CLP; Group V: 50/mg/kg/day dosage of i.p pentoxifylline treatment was applied for 72 hours after CLP. All rats were sacrificed on the seventh day of this study. Malondialdehyde (MDA), Glutathione Peroxidase (GPx), Superoxide Dismutase (SOD), catalase, Tumor Necrotic Factor-alpha (TNF-α) levels, and tissue (lung, kidney) and serum samples were taken for histopathological study. When compared to the control group, the tissue damage score was found to be lower in all treatment groups. Sildenafil, milrinone and NAS groups had higher kidney GPx levels compared to the control group. Milrinone and pentoxifylline were higher in the lung tissue compared to the SOD control group. TNFα levels were lower in pentoxifylline and milrinone groups compared to the control group. This experimental study has shown that PDE inhibitors and NAS have a decreasing effect on oxidative stress and distant organ damage in the two-hit model. Further clinical and experimental studies are needed on this subject.

Investigating the effect of sildenafil on improving lung function and quality of life in the patients with severe asthma.

Introduction:Phosphodiesterase inhibitors (PDEs) increase intracellular cyclic adenosine monophosphate, which results in a wide range of anti-inflammatory effects and pathologically leads to improve asthma disease. Because no human study has surveyed the effect of PDEs on pulmonary function, except some case reports and animal researches, we decided to perform a pilot study for evaluating the effect of sildenafil (PDE5) on pulmonary function in patients with severe asthma.Methods:This randomized controlled trials study was conducted on 20 patients with severe asthma in 2019 in Iran. For case group, was prescribed sildenafil (50 mg) daily and the control group received the placebo. In the beginning of the study and one month later, volume parameters, 6-minute walk distance (6MWD), and the quality-of-life questionnaire were measured and compared in the two groups.Results:Twenty patients were entered into this study. 8 patients (40%) were male and 12 (60%) were female. The results showed that mean forced vital capacity 1 in the sildenafil group turned from 1259 ± 170 to 1603 ± 527, while in the placebo group it changed from 1135 ± 125 to 1365 ± 251 (P-value = 0.215). There is no statistically significant difference between two groups. In addition, in comparison with placebo, sildenafil did not show any significant improvement in the volume parameters, the quality-of-life questionnaire scale, and 6MWD at the end of the study.Conclusion:According to present result can be concluded that sildenafil does not improve the severity of asthma and the quality of life in patients with severe asthma.

The Clinical Effects of Sildenafil for Erection in Patients after Kidney Transplantation: A Meta-Analysis

Background: With the wide use of sildenafil in kidney-transplanted patients, it is vital to recognize the effectiveness and safety in clinical practice. Methods: Full-text articles involving the application of sildenafil after renal transplantation searched out in multiple databases were reviewed. All the meta-analyses were performed with Review Manager 5.0 software and bias analysis of the studies were conducted to examine the quality of articles. In addition, to estimate possible publication bias, funnel plot and the Egger’s test were used. Result: Finally 7 articles eventually satisfied the inclusion criteria. The penetration ability and maintenance frequency in sildenafil group were much larger than those of control group. Except orgasmic function, domains of the International Index of Erectile Function have showed larger scores in sildenafil group than those of control group. No significant difference of the concentration of cyclosporine was observed between sildenafil and control group. Conclusion: In conclusion, this study showed that treatment with sildenafil in renal allograft recipients with erectile dysfunction is a valid and safe option.

Pulmonary Artery Denervation Significantly Increases 6-Min Walk Distance for Patients With Combined Pre- and Post-Capillary Pulmonary Hypertension Associated With Left Heart Failure: The PADN-5 Study

ObjectivesThe authors sought to assess the benefits of pulmonary artery denervation (PADN) among combined pre- and post-capillary pulmonary hypertension (CpcPH) patients in a prospective, randomized, sham-controlled trial. BackgroundPADN has been shown to improve hemodynamics of pulmonary arterial hypertension in a series of patients. Additionally, benefits of targeted medical therapy for patients with CpcPH secondary to left-sided heart failure are unknown. MethodsNinety-eight CpcPH patients, defined as mean pulmonary arterial pressure ≥25 mm Hg, pulmonary capillary wedge pressure >15 mm Hg, and pulmonary vascular resistance (PVR) >3.0 Wood units (WU), were randomly assigned to PADN or sildenafil plus sham PADN. Standard medical therapy for heart failure was administered to all patients in both groups. The primary endpoint was the increase in the 6-min walk distance at the 6-month follow-up. The secondary endpoint was change in PVR. Clinical worsening was assessed in a post hoc analysis. The main safety endpoint was occurrence of pulmonary embolism. ResultsAt 6 months, the mean increases in the 6-min walk distance were 83 m in the PADN group and 15 m in the sildenafil group (least square mean difference 66 m, 95% confidence interval: 38.2 to 98.8 m; p < 0.001). PADN treatment was associated with a significantly lower PVR than in the sildenafil group (4.2 ± 1.5 WU vs. 6.1 ± 2.9 WU; p = 0.001). Clinical worsening was less frequent in the PADN group compared with the sildenafil group (16.7% vs. 40%; p = 0.014). At the end of the study, there were 7 all-cause deaths and 2 cases of pulmonary embolism. ConclusionsPADN is associated with significant improvements in hemodynamic and clinical outcomes in patients with CpcPH. Further studies are warranted to define its precise role in the treatment of this patient population. (Pulmonary Arterial Denervation in Patients With Pulmonary Hypertension Associated With the Left Heart Failure [PADN-5]; NCT02220335)

Phosphodiesterase type 5 inhibitors improve microvascular dysfunction markers in pulmonary arterial hypertension associated with congenital heart disease.

Ideally, vasodilator therapies for pulmonary arterial hypertension (PAH) should have a favorable impact on markers of vascular dysfunction, in addition to their known effects on hemodynamics, cardiac function, and patient's physical capacity. We analyzed circulating (plasma) markers of endothelial and platelet activation/dysfunction (enzyme-linked immunoassays) in the specific setting of advanced PAH associated with congenital heart disease, during the course of sildenafil and tadalafil therapies. Thirty-one patients were enrolled (age 10-54years), most of them with chronic hypoxemia and elevated hematocrit. Drugs were administered orally for 6months (sildenafil [n=16], 20mg t.i.d.; tadalafil [n=15], single daily dose of 40mg). Measurements were performed at baseline, and 90 and 180days. Compared to controls, patients had elevated baseline β-thromboglobulin (β-TG, P=.002), P-selectin (P=.027), tissue-type plasminogen activator (t-PA, P=.009), and von Willebrand factor antigen (VWF:Ag, P=.010). Thrombomodulin was importantly reduced (TM, P<.001), while soluble CD40 Ligand was not changed (P=.320). Tadalafil administration was associated with improvement of β-TG (P=.004), t-PA (P=.003) and TM (P=.046) levels, while P-selectin was improved by sildenafil treatment only (P=.034). VWF:Ag improved transiently in the sildenafil group (P=.019). Both therapies were associated with improvement of the physical capacity (functional class and distance walked during the 6-minute test, P<.05), hematocrit and hemoglobin level (P<.05), and health-related quality of life (physical and mental components, P<.05). In PAH associated with congenital heart disease, phosphodiesterase 5 inhibitors seem to have beneficial actions at microcirculatory level, beyond the proposed effects as vasodilators.

THE FIBRINOLYTIC ALTERATION ASSOCIATED WITH DAILY ADMINISTRATION OF SILDENAFIL

Objective: The objective of this study was to determine the fibrinolytic alteration associated with daily administration of sildenafil.Methods: A total of 12 adult male rabbits without mortality rate had been fed standard and subdivided into four groups; their average weight was 1.5, 2.5, 1.9, and 2 kg randomly selected during the period of March 2012–July 2013. Depending on weight, the control groups (2.25 mg/1.5 kg day) and sildenafil groups (3 mg/2 kg/day, 2.85 mg/1.9 kg/day, and 1.7 mg/2.5 kg/day) were injected by normal saline and sildenafil concentration, respectively to create four groups, every group was composed of three rabbits; saline rabbit (control group, n=3) and sildenafil rabbits (sildenafil group, n=9). All rabbit’s plasma samples have been investigated for prothrombin time, activated partial thromboplastin time, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), prothrombin fragment 1+2, tissues plasminogen activator (tPA), plasmin antiplasmin (PAP), plasminogen, and D-dimer after 24 h of administration.Results: The PAP level was significantly (p&lt;0.05) decreased following sildenafil injection. Sildenafil-injected (3 mg/ml) rabbits had decreased the means of PAI-1 and mean tPA, as early as 1-day post-injection, with a considerable lower PAP first determined 3 days after injection that continued into each rabbit 2 and 3.Conclusion: Better strategies are to initiate and manipulate this drug ought to reduce the chance of each thrombosis and hemorrhage, at the same time as minimizing the need for laboratory monitoring with the aid of the use of PAI-1, tPA, and PAP checks.

Use of sildenafil citrate in cases of intrauterine growth restriction (IUGR); a prospective trial

ObjectiveIntrauterine growth restriction (IUGR) is one of the most serious complications of pregnancy. Up to date, there is no evidence of achieving antenatal treatment of IUGR with abnormal placentation. Although, Sildenafil citrate has shown promising results, there are no firm conclusion till now. The aim of our study is to evaluate the use of Sildenafil citrate in the treatment of IUGR cases associated with impaired placental circulation. Materials and methodsThis was a prospective non-randomized study conducted at Mansoura university hospitals starting from March 2016 till October 2017. The studied population included singleton pregnancy and suffering from IUGR associated with impaired placental circulation. ResultsThis study included 50 pregnant women. Cases were divided into two groups. The first group received sildenafil citrate and the second control group did not receive sildenafil citrate. After 4 weeks after the 1st dose of Sildenafil significant decrease in umbilical artery Doppler indices. There was a statistically significant difference in the mean birth weight at delivery and neonatal admission to the newborn nursery in sildenafil group. Conclusionsildenafil citrate treatment may present a new hope towards better perinatal outcomes for pregnancies complicated by IUGR and impaired placental circulation that may help to decrease neonatal admission to the newborn nursery.

Pulmonary Artery Denervation Significantly Increases 6-Minute Walk Distance for Patients with Pulmonary Hypertension Associated with Left-Side Heart Failure: A Prospective, Randomized, and Sham-Controlled PADN-5 Study

Background: Heart failure (HF) is associated with sympathetic overactivation. Combined pre-capillary and post-capillary pulmonary hypertension (CpcPH) bears the same pathology as pulmonary arterial hypertension (PAH). Benefits of targeted-PAH medications for CpcPH patients are unknown. Pulmonary artery denervation (PADN), which showed benefit for both PAH and PH patients in a previous consecutive registry study, has not been studied in CpcPH patients using a randomized design. We therefore sought to assess the benefits of PADN for CpcPH patients. Methods: Of 865 patients with HF who were stable for ≥ 3 months and were admitted due to recent worsening of symptoms were enrolled, 387 patients after at least 3 days of treatment had a systolic pulmonary arterial pressure (PAP) ≥ 45 mmHg measured by echocardiography. Among them, 98 CpcPH patients (mean PAP≥25 mmHg, pulmonary capillary wedge pressure >15 mmHg, and pulmonary vascular resistance [PVR] > 3·0 Wood units) were randomly assigned to receive sildenafil plus anti-HF medication and sham PADN or PADN plus anti-HF medication without sildenafil. The primary endpoint was an increase in the 6-minute walk distance (6MWD) at the 6-month followup. PVR and clinical worsening were secondary endpoints. Pulmonary embolism was a safety endpoint. Findings: At the 6-month follow-up, the mean increases in the 6MWD were 83 m in the PADN group and 15 m in the sildenafil group ((least square mean difference 66 m, 95% confidence interval= 38·2-98·8; p<0·001). A 1-SD decrease in the 6MWD was strongly correlated with clinical worsening (corresponding hazard ratio [95% confidence interval] =3·02[ 1·05-8·74]; p=0·04). PADN treatment was associated with significant reduction (29·8%) in PVR and lower rate (16·7%) of clinical worsening, compared with 3·4% (hazard ratio [95% confidence interval] =4·73 [2·05-10·89]; p<0·001) and 40% (hazard ratio [95% confidence interval] =3·33 [1·29-8·59]; p=0·014) in the sildenafil group. At the end of the study, there were 7 all-cause deaths (5 in the sildenafil and 2 in the PADN group) and 2 embolisms (1 in each group). Interpretation: PADN is associated with significant improvements in hemodynamic parameters, cardiac function, and clinical outcomes, when compared with those after 6-month sildenafil treatment. Further studies are warranted to confirm the reduction of CpcPH-related events by PADN. Clinical Trial Number: Registration at clinicaltrials.com; identifier: NCT02220335 Funding Statement: National Science Foundation of China (NSFC 91639303 and NSFC 81770441). Declaration of Interests: CSL is the inventor of PADN patent, but not the owner. The remaining authors have nothing to disclosure. Ethics Approval Statement: The PADN-5 trial is a 4-center, randomized, and sham-controlled clinical trial, which was approved by the ethics committee at each participating center. All patients provided written informed consent. Sponsors had no access to the trial data and no role in the design, conduct, or reporting of the results. Clinical events were adjudicated by an independent committee.

100 Avanafil 200 mg Vs Sildenafil 100 mg Post Nerve Sparing Robotic Prostatectomy: a Multicentric Prospective Randomized Trial

Nowadays, Phosphodiesterase type 5 inhibitors are considered to be the first line therapy for erectile dysfunction secondary to nerve sparing radical prostatectomy,each of them with its own pharmacokinetic features and profiles of efficacy and safety. We evaluated the efficacy and safety of avanafil 200 mg three times a week compared to the same sildenafil 100 mg therapy. We enrolled 301 candidates for nerve sparing robot assisted prostatectomy from January 2016 to July 2017 with following preoperative criteria: Charlson Comorbidity Index (CCI) ≤1, ECOG performance status ≤1, International index of erectile function (IIEF) 15> 17, EHS> 2, positive response to Sexual Encounter Profile(Sep) q2 and Sepq3, Quality of Life <3 and finally one sexual intercourse por week. Only 220 were eligible for the study. Patients were randomized into two groups: avanafil 200 mg group (A group) and 100 mg sildenafil group (S Group).After removal of the bladder catheter at the tenth postoperative day, they started rehabilitation therapy three times a week for three months. At the third months, the validated measures of erectile function (IIEF 15, SEPq2-q3, Ehs) and Qol, Gaq1-2 were administered and we evaluated the number of weekly sexual intercourse. Randomization was performed by each center with Randomizer Research and statistical analysis was performed using Chi-Square and Wilcoxon-Mann-Whitney tests, as appropiated. All analyses were performed with MedCalc Statistical Software version 15.8.

Beneficial effects of fenofibrate in pulmonary hypertension in rats.

Pulmonary hypertension(PH) is a morbid complication of cardiopulmonary as well as several systemic diseases in humans. It is rapidly progressive and fatal if left untreated. In the present study, we investigated the effect of PPARα agonist fenofibrate (FF) on monocrotaline (MCT)-induced PH in rats. FF, because of its pleiotropic property, could be helpful in reducing inflammation, oxidative stress, and reactive oxygen species. On day 1, MCT (50mg/kg, s.c.) was given to all the rats in MCT, sildenafil, and FF group except normal control rats. After 3 days of giving MCT, sildenafil (175µg/kg, orally) and FF (120mg/kg, orally) were given for 25 days. Echocardiography, hemodynamic parameters, fulton's index, histopathology, oxidative stress parameters, inflammatory markers, Bcl2/Baxgene expression ratio in the right ventricle, and protein expressionfor NOX-1 in lungs were studied in all the groups. FF has shown to prevent decrease in ratio of pulmonary artery acceleration time to ejection time, increase in ratio of right ventricular outflow tract dimension to aortic outflow dimension, rise in right ventricular systolic pressure, right ventricular hypertrophy, increase in the percentage medial wall thickness (%MWT), increase in oxidative stress and inflammation, increase in NADPH oxidase-1 (NOX-1) expression, and decrease in mRNA expression of Bcl2/Bax ratio caused by MCT. To conclude, FF prevented MCT-induced PH in rats by various mechanisms. It might be helpful in preventing PH in patients who are likely to develop PH.