sildenafil-citrate and Pulmonary-Disease--Chronic-Obstructive

Pulmonary hypertension (PH) is a severe and prevalent complication of chronic obstructive pulmonary disease (COPD), with low quality of life and poor prognosis. This study was designed to evaluate the efficacy and safety of Sildenafil in the treatment of PH caused by COPD (COPD-PH) and provide reference for clinical treatment.. We systematically searched PubMed, EMBASE, Cochrane Library, Clinical Trials.gov databases, Wanfang Data and CNKI for comprehensive literature reporting Sildenafil for randomized controlled trials (RCT) of COPD-PH. Quality assessment, data analysis used the modified Jadad scale and RevMan5.3 software.. A total of 9 RCTs involving 579 patients were included in our study. The primary outcome measure was Six minutes walking distance (6MWD). Secondary observations were Pulmonary artery systolic pressure (PASP), Borg dyspnea index, and Survey scale (SF-36). Our data demonstrate that Sildenafil can improve 6WMD [29.64, 95% CI (13.78, 45.50), P < 0.00001] and PASP [-7.86, 95% CI (-11.26, -4.46) P < 0.00001] of COPD-PH, compared with the control group. However, SF-36 [2.64, 95% CI (-6.85, 12.14) P = 0.59] and Borg dyspnea index [-0.28, 95% CI (-1.08, 0.52) P = 0.49] have no significant difference between those two groups. Adverse reactions in the Sildenafil treatment group were tolerated headaches and digestive symptoms, which were relatively safe.. Available clinical evidence indicates that Sildenafil seems to be safe and effective for COPD-PH and can improve the patients' 6WMD. However, large-sample, high-quality multicenter RCTs are still needed to provide stronger evidence-based medical evidence.

Topics: Humans; Hypertension, Pulmonary; Pulmonary Disease, Chronic Obstructive; Sildenafil Citrate; Treatment Outcome

Some patients with chronic obstructive pulmonary disease (COPD) have pulmonary hypertension (PH) that adversely affects survival. We performed a systematic review and meta-analysis to assess whether PH-specific therapies have an effect for stable COPD. Data sources were Medline, EMBASE, Cochrane Central Register of Controlled Trials, Korea med and references from relevant publications. Randomized prospective trials that compared PH specific therapy in COPD for more than 6 weeks with placebo were included. The outcomes were the exercise capacity and adverse events. Four randomized controlled trials involving 109 subjects were included in the analysis. Two trials involved bosentan, one sildenafil and one beraprost. The studies varied in duration of treatment from 3 to 18 months. In a pooled analysis of four trials, exercise-capacity was not significantly improved with PH-specific treatment for COPD (risk ratio, -5.1; 95% CI, -13.0 to 2.8). COPD with overt PH significantly improved the exercise capacity (mean difference, 111.6; 95% CI, 63.3 to 159.9) but COPD with PH unknown did not (mean difference, 26.6; 95% CI, -24.3 to 77.5). There was no significant difference in hypoxemia (mean difference, 2.6; 95% CI, -3.7 to 8.8). PH specific treatments have a significant effect in improving exercise capacity in COPD with overt PH.

Topics: Antihypertensive Agents; Bosentan; Clinical Trials as Topic; Databases, Factual; Epoprostenol; Humans; Hypertension, Pulmonary; Hypoxia; Piperazines; Pulmonary Disease, Chronic Obstructive; Purines; Risk Factors; Sildenafil Citrate; Sulfonamides; Sulfones; Surveys and Questionnaires

Erectile dysfunction (ED) is a well-known entity with determined risk factors, which generally has a negative impact on quality of life. Obstructive sleep-disordered breathing (SDB), often referred to as obstructive sleep apnea, stands among the possible risk factors for ED.. Literature review suggests that SDB induces a spectrum of abnormalities in neural, hormonal, and vascular regulation that may contribute to the development of ED. While more studies are required to imply SDB as a risk factor for ED, several case series and expert opinion have contributed evidence for a causal relationship.. In clinical practice, men presenting with symptoms of sexual dysfunction often have concomitant sleep disorders requiring treatment. There is now evidence to suggest that treating SDB may be an effective treatment for ED. It is the authors' opinion that patients with erectile dysfunction would benefit from a sleep evaluation.

Topics: Aged; Cardiovascular Diseases; Continuous Positive Airway Pressure; Diabetes Mellitus, Type 2; Erectile Dysfunction; Humans; Hypertension; Kidney Failure, Chronic; Male; Middle Aged; Obesity; Phosphodiesterase Inhibitors; Piperazines; Prevalence; Pulmonary Disease, Chronic Obstructive; Purines; Quality of Life; Risk Factors; Sildenafil Citrate; Sleep Apnea, Obstructive; Sulfones

Three different phosphodiesterase 5 (PDE5) inhibitors are currently available for the treatment of erectile dysfunction: sildenafil, vardenafil and tadalafil. The differences between these 3 are limited: tadalafil has a long duration of action, while vardenafil has a rapid onset of action after intake. Various studies have suggested that there is an improvement in the partners' sex lives when men use a PDE5 inhibitor for erectile dysfunction. The introduction of PDE5 inhibitors has renewed the interest in PDE inhibitors in general, for example in the treatment of pulmonary hypertension. In the near future PDE inhibitors may be used for various disorders as chronic obstructive pulmonary disease, benign prostatic hyperplasia, hypertension and coronary heart disease.

Topics: Carbolines; Coronary Disease; Erectile Dysfunction; Humans; Hypertension; Imidazoles; Male; Phosphodiesterase Inhibitors; Piperazines; Prostatic Hyperplasia; Pulmonary Disease, Chronic Obstructive; Purines; Sildenafil Citrate; Sulfones; Tadalafil; Treatment Outcome; Triazines; Vardenafil Dihydrochloride

Pulmonary hypertension is a common complication of chronic obstructive pulmonary disease (COPD). The increase in pulmonary artery pressures is often mild to moderate. However, 5-10% of patients with advanced COPD may suffer from severe pulmonary hypertension and present with a progressively downhill clinical course because of right heart failure added to ventilatory handicap. The prevalence of clinically significant severe pulmonary hypertension in COPD is roughly estimated to be of 1-2/1,000. The cause of pulmonary hypertension in COPD is generally assumed to be hypoxic pulmonary vasoconstriction leading to permanent medial hypertrophy. However, recent pathologic studies point rather at extensive remodeling of all layers of the pulmonary arterial walls. These aspects account for minimal reversibility with supplemental oxygen. There may be a case for pharmacologic treatment of pulmonary hypertension in selected patients with advanced COPD and right heart failure. However, it will be a challenge for randomized controlled trials to overcome the difficulties of the diagnosis of right ventricular failure and the definition of a relevant primary endpoint in pulmonary hypertensive patients with COPD.

Topics: Antihypertensive Agents; Bosentan; Humans; Hypertension, Pulmonary; Piperazines; Pulmonary Disease, Chronic Obstructive; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Vasodilator Agents; Ventricular Dysfunction, Right

Pulmonary hypertension (PH) occurs frequently in parenchymal lung disease and is usually correlated with increased mortality. Thus, the treatment of PH in patients with lung disease has been an active area of interest. Secondary pulmonary hypertension (SPH), whether from parenchymal lung disease or other etiologies, is more common than primary pulmonary hypertension (PPH). In 2002, two new medications, oral bosentan and subcutaneous treprostinil, were released for the treatment of pulmonary arterial hypertension (PAH). These new agents are not restricted to use in PPH, as they are approved for use in PAH in general. It is reasonable to consider the use of these medications in select patients with SPH caused by parenchymal lung disease, although these groups have not yet been studied in clinical trials. The initial hemodynamic evaluation of SPH patients, the potential use of these new medications in the context of standard care, and the assessment of response to therapy are discussed in this update. A relevant case report is used to illustrate use of these new agents in SPH, and ongoing clinical trials are reviewed. The available treatment options for patients with SPH are rapidly improving.

Topics: Antihypertensive Agents; Bosentan; Cardiac Catheterization; Clinical Trials as Topic; Echocardiography; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Middle Aged; Piperazines; Pulmonary Disease, Chronic Obstructive; Purines; Sildenafil Citrate; Sulfonamides; Sulfones; Vasodilator Agents

Pulmonary hypertension (PH) is a well-known independent prognostic factor in chronic obstructive pulmonary disease (COPD) and a sufficient criterion for lung transplant candidacy. Limited data are currently available on the hemodynamic and clinical effect of phosphodiesterase 5 inhibitors in patients with severe PH associated with COPD. This study assessed the effect of sildenafil on pulmonary hemodynamics and gas exchange in severe PH associated with COPD.. After screening, this multicenter, randomized, placebo-controlled double-blind trial randomized patients to receive 20 mg sildenafil or placebo 3 times a day (ratio 2:1) for 16 weeks. The primary end point was the reduction in pulmonary vascular resistance. Secondary end points included BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, 6-minute walk test, and quality of life questionnaire. Changes in the partial pressure of arterial oxygen were evaluated as a safety parameter.. The final population included 28 patients, 18 in the sildenafil group and 10 in the placebo group. At 16 week, patients treated with sildenafil had a decrease in pulmonary vascular resistance (mean difference with placebo -1.4 WU; 95% confidence interval, ≤ -0.05; p = 0.04). Sildenafil also improved the BODE index, diffusion capacity of the lung for carbon monoxide percentage, and quality of life. Change from baseline in the partial pressure of arterial oxygen was not significantly different between the sildenafil and placebo groups.. This pilot study found that treatment with sildenafil reduced pulmonary vascular resistance and improved the BODE index and quality of life, without a significant effect on gas exchange.

Topics: Adult; Aged; Aged, 80 and over; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Patient Selection; Pilot Projects; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Reference Values; Risk Assessment; Severity of Illness Index; Sildenafil Citrate; Treatment Outcome; Vascular Resistance

Pulmonary hypertension is a serious complication of chronic obstructive pulmonary disease (COPD) that currently has no established pharmacological treatment. This study aimed to assess whether concomitant treatment with sildenafil would enhance the results of pulmonary rehabilitation in patients with COPD and increased pulmonary arterial pressure (PAP). In this double-blind, randomised controlled trial patients received 20 mg sildenafil or placebo three times daily and underwent pulmonary rehabilitation for 3 months. The primary end-point was the gain in the cycle endurance time at a constant work-rate. Secondary end-points included performance in the incremental exercise test, 6-min walk distance and quality of life. 63 patients with severe COPD and moderately increased PAP were randomised. Cycle endurance time increased by 149 s (95% CI 26-518 s) in the sildenafil group and by 169 s (95% CI 0-768 s) in the placebo group (median change difference -7 s, 95% CI -540-244 s; p=0.77). Gains in the incremental exercise test, 6-min walk distance and quality of life at the end of the study did not differ between groups. Measurements of arterial oxygenation and adverse events were similar in both groups. In patients with severe COPD and moderately increased PAP, concomitant treatment with sildenafil does not improve the results of pulmonary rehabilitation in exercise tolerance.

Topics: Aged; Arterial Pressure; Double-Blind Method; Exercise Test; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Piperazines; Placebos; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Purines; Quality of Life; Sildenafil Citrate; Sulfones; Time Factors; Treatment Outcome; Vasodilator Agents

Sildenafil decreases pulmonary vascular resistance index (PVRI), in patients with pulmonary hypertension (PH). We investigated sildenafil's effects on central hemodynamics of mechanically ventilated patients with WHO group-III PH and RV failure necessitating dobutamine administration.. Prospective non-controlled study involving 12 (9 males, 59 ± 4 years old), patients with the above characteristics. All patients in phase-1 (days 1-2) received dobutamine (5 μg/kg/min IV). During phase-2 (days 3-6), sildenafil was started via nasogastric tube (80 mg/day) and dobutamine discontinuation was attempted. Patients were designated responders or non-responders based on whether dobutamine could be stopped or not. Phase-3 lasted from day 7 to day of weaning from mechanical ventilation; or if weaning failed, until day 20 following admission (end-of-study). Invasive and echocardiographic parameters were repeatedly recorded throughout the study.. Significantly changed parameters (P<0.025) from baseline to phase-1, -2 and -3 (%change of mean ratios), in responders (n=7) included among others PVRI (-40%, -51%, -42%), RV stroke work index (RVSWI: 43%, 79%, 41%) and cardiac index (49%, 54%, 48%), which also differed significantly from non-responders (N=5). In phases-1 and -3 non-responders had not significant changes, in phase-2 PVRI (27%) and RVSWI (-22%) changed significantly. In contrast to non-responders, all responders were weaned from mechanical ventilation until the end-of-study (P<0.025).. Sildenafil may improve central hemodynamics and RV function indices in ventilated patients with WHO group-III PH and RV failure requiring dobutamine infusion, when they respond favorably to the latter. Accordingly, an adequate RV systolic reserve may be mandatory for sildenafil to exert its actions.

Topics: Adrenergic beta-1 Receptor Agonists; Dobutamine; Female; Heart Failure; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Phosphodiesterase 5 Inhibitors; Piperazines; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Purines; Respiration, Artificial; Sildenafil Citrate; Sulfones; Time Factors; Treatment Outcome; Ventricular Dysfunction, Right

Pulmonary hypertension with exercise is common in chronic obstructive pulmonary disease (COPD) and may contribute to exercise limitation in this disease. We aimed to determine the effects of treatment with sildenafil on exercise capacity in patients with COPD and emphysema.. We performed a randomized, double-blind, placebo-controlled 2-period crossover trial of sildenafil thrice daily in ten adults with COPD and emphysema on CT scan without pulmonary hypertension. We randomized study participants to 4 weeks of sildenafil (or placebo) followed by a 1-week washout and then 4 weeks of placebo (or sildenafil). The 2 primary outcomes were the 6-minute walk distance and oxygen consumption at peak exercise.. Sildenafil had no effect on 6-minute walk distance (placebo-corrected difference = -7.8 m, 95% confidence interval, -23.2 to 7.5 m, p = 0.35) or oxygen consumption at peak exercise (placebo-corrected difference = -0.1 ml/kg/min, 95% confidence interval -2.1 to 1.8 ml/kg/min, p = 0.89). Sildenafil increased the alveolar-arterial oxygen gradient (p = 0.02), worsened symptoms (p = 0.04), and decreased quality-of-life (p = 0.03). Adverse events were more frequent while receiving sildenafil (p = 0.005).. Routine sildenafil administration did not have a beneficial effect on exercise capacity in patients with COPD and emphysema without pulmonary hypertension. Sildenafil significantly worsened gas exchange at rest and quality of life. (clinicaltrials.gov NCT00104637).

Topics: Aged; Cross-Over Studies; Double-Blind Method; Exercise Test; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Oxygen Consumption; Piperazines; Pulmonary Disease, Chronic Obstructive; Purines; Quality of Life; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents

Chronic Obstructive Pulmonary Disease (COPD) is a common disease that tends to occur worldwide and is a common cause of respiratory failure requiring mechanical ventilation and admission to the intensive care unit (ICU). The present study was carried out to investigate the efficacy of sildenafil in facilitating the weaning of COPD patients from the ventilator.. This randomized double blind clinical trial study was carried out with 40 patients suffering from COPD. The patients were divided in two study groups. 20 patients belonging to Group I received 20 mg sildenafil tablets twice a day for one week while 20 patients of the second group (Group II) received placebo tablets with the same dosage. Respiratory parameters like rapid shallow breathing index (RSBI), mixed venous oxygen pressure (PvO2) and plateau pressure were measured in both groups. Data were analyzed on the basis of student's t-test and Chi2 test using SPSS 16 software.. The results are expressed as mean +/- SE and P < 0.05 is considered statistically significant. According to our findings RSBI was lower in Group I compared with Group II after one week of treatment (P = 0.032). PvO2 value was higher in sildenafil group compared with placebo group (P = 0.025). Plateau pressure was lower in first group than group II (P = 0.022).. Sildenafil facilitated weaning of COPD patients from the ventilator by improving the respiratory parameters.

Topics: Double-Blind Method; Female; Humans; Intensive Care Units; Male; Middle Aged; Oxygen; Phosphodiesterase 5 Inhibitors; Piperazines; Pulmonary Disease, Chronic Obstructive; Purines; Respiration; Respiration, Artificial; Sildenafil Citrate; Sulfones; Vasodilator Agents; Ventilator Weaning

There is a high incidence of pulmonary hypertension during the lung transplant peri-operative period, and could lead to a haemodynamic deterioration that may require the need of extracorporeal circulation. Our aim was to study the haemodynamic effects on the pulmonary and systemic circulation of the combination of inhaled nitric oxide and iloprost and oral sildenafil in patients with severe pulmonary hypertension during lung transplant surgery.. Seventeen patients received 10μg of nebulised iloprost during the peri-operative period of the lung transplant when their mean pulmonary pressure exceeded 50mmHg. AU the patients received 50mg of oral sildenafil 30min before anaesthetic induction, 20ppm of inhaled nitric oxide after tracheal intubation. The haemodynamic and respiratory variables were recorded at baseline (after anaesthetic induction), prior to the administering of iloprost, and at 5 and 30min after it was given.. The administering of iloprost significantly reduced the pulmonary arterial pressure and significantly increases the cardiac Índex and the right ventrícular ejection fractíon. There were no signíficant changes occurred in the systemic arterial pressure.. The triple combination significantly reduces the pulmonary pressures in the lung transplant peri-operative and should be considered when there is severe pulmonary hypertension during the surgery or during the immediate post-operative period of lung transplantation.

Topics: Administration, Inhalation; Administration, Oral; Adult; Aged; Cystic Fibrosis; Dobutamine; Drug Therapy, Combination; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Iloprost; Intraoperative Complications; Lung Transplantation; Male; Middle Aged; Nebulizers and Vaporizers; Nitric Oxide; Norepinephrine; Piperazines; Preoperative Care; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents

Sildenafil, a phosphodiesterase-5 inhibitor, could be useful for treating pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). However, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange in this condition.. To assess the acute hemodynamic and gas exchange effects of sildenafil in patients with COPD-associated PH.. We conducted a randomized, dose comparison trial in 20 patients with COPD-associated PH. Eleven patients were assigned to 20 mg, and 9 patients to 40 mg, of sildenafil. Pulmonary hemodynamics and gas exchange, including ventilation-perfusion (V(A)/Q) relationships, were assessed at rest and during constant-work rate exercise, before and 1 hour after sildenafil administration.. Both sildenafil doses reduced the mean pulmonary arterial pressure (PAP) at rest and during exercise, without differences between them. Overall, PAP decreased -6 mm Hg (95% confidence interval [95% CI], -7 to -4) at rest and -11 mm Hg (95% CI, -14 to -8) during exercise. After sildenafil, Pa(O(2)) decreased -6 mm Hg (95% CI, -8 to -4) at rest because of increased perfusion in units with low V(A)/Q ratio, without differences between doses. No change in Pa(O(2)) (95% CI, -3 to 0.2 mm Hg) or V(A)/Q relationships occurred during exercise after sildenafil. Changes induced by sildenafil in Pa(O(2)) and V(A)/Q distributions at rest correlated with their respective values at baseline.. In patients with COPD-associated PH, sildenafil improves pulmonary hemodynamics at rest and during exercise. This effect is accompanied by the inhibition of hypoxic vasoconstriction, which impairs arterial oxygenation at rest. The use of sildenafil in COPD should be done cautiously and under close monitoring of blood gases. Clinical trial registered with www.clinicaltrials.gov (NCT00491803).

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Aged; Dose-Response Relationship, Drug; Exercise; Exercise Test; Female; Follow-Up Studies; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Piperazines; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Pulmonary Wedge Pressure; Purines; Rest; Severity of Illness Index; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents

In chronic obstructive pulmonary disease (COPD) patients, stroke volume response to exercise is impaired. The aim of the present study was to investigate whether 3 months of sildenafil treatment improves stroke volume and, if so, whether this improvement is related to the pulmonary artery pressure and translated into an improved exercise capacity. A total of 15 stable COPD patients (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) underwent right heart catheterisation at rest and during exercise. Stroke volume was assessed by magnetic resonance imaging (MRI) at rest and during submaximal exercise in the supine position and compared with eight age-matched controls. Additionally, a cardiopulmonary exercise test and a 6-min walking distance test were performed. Exercise tests and MRI were repeated after 12 weeks of oral therapy with 50 mg sildenafil three times daily. Stroke volume in COPD patients was significantly lower than in healthy controls (62+/-12 versus 81+/-22 mL at rest and 70+/-15 versus 101+/-28 mL during exercise). Pulmonary hypertension (PH) was diagnosed in nine patients and was absent in six. Treatment with sildenafil had no effect on stroke volume or exercise capacity. Although the stroke volume was lower in COPD patients with associated PH in comparison with non-PH patients, there was no difference in treatment response between both groups. In the present group of 15 chronic obstructive pulmonary disease patients, a reduced stroke volume was found at rest and during exercise. Neither stroke volume nor exercise capacity were improved by 3 months of sildenafil therapy.

Topics: Aged; Case-Control Studies; Exercise Test; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Piperazines; Pulmonary Disease, Chronic Obstructive; Purines; Sildenafil Citrate; Stroke Volume; Sulfones; Vasodilator Agents

We investigated in chronic obstructive pulmonary disease (COPD) patients whether a single dose of sildenafil can attenuate the exercise-induced increase in pulmonary artery pressure, thereby allowing augmentation of stroke volume (SV), and improving maximal exercise capacity.. Eighteen COPD patients (GOLD II-IV) underwent right heart catheterization at rest and submaximal exercise. Mean pulmonary artery pressure (mPpa) and cardiac output (CO) were assessed. Resting and exercise measurements were repeated 60 min after oral intake of 50mg sildenafil. Also, on different days, patients performed two maximal exercise tests (CPET) randomly, 1h after placebo and after 50mg sildenafil.. Five COPD patients had pulmonary hypertension (PH) at rest (mPpa >25 mmHg) and six developed PH during exercise (mPpa >30 mmHg). In all patients, mPpa increased from rest to submaximal exercise (23+/-10-35+/-14 mmHg). After sildenafil mPpa at rest was 20+/-10 mmHg, in exercise mPpa was increased less to 30+/-14 mmHg (p<0.01). The reduced augmentation in mPpa was not accompanied by an increased SV and CO. In COPD patients with PH the percentage increase in mPpa to submaximal exercise was 68% before, and 51% after oral intake of sildenafil (p=0.07). In COPD without PH, these values were 46% and 41% (ns), respectively. Maximal exercise capacity and CPET characteristics were unchanged after sildenafil.. Regardless of mPpa at rest, sildenafil attenuates the increase in mPpa during submaximal exercise in COPD. This attenuated increase is neither accompanied by enhanced SV and CO, nor by improved maximal exercise capacity.

Topics: Aged; Anaerobic Threshold; Cardiac Catheterization; Cardiac Output; Exercise Test; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Male; Middle Aged; Oxygen; Piperazines; Pulmonary Circulation; Pulmonary Disease, Chronic Obstructive; Pulmonary Wedge Pressure; Purines; Sildenafil Citrate; Stroke Volume; Sulfones; Vasodilator Agents; Ventricular Function, Right

Pulmonary hypertension (PH) is an important predictor of mortality in chronic obstructive pulmonary disease (COPD). The phosphodiesterase 5 inhibitor sildenafil has been demonstrated to reduce pulmonary arterial pressure (PAP) in different diseases. We wanted to investigate the effect of sildenafil on hemodynamic parameters and the 6-min walk test (6 MWT) in six patients with severe COPD and echocardiographically estimated PH. A 6 MWT was performed and hemodynamic parameters were measured by right heart catheterization before and 1 and 12h after injection of 50mg sildenafil intravenously. A 3-months period of peroral sildenafil therapy 50mg twice daily followed and finally hemodynamic parameters and a 6 MWT were repeated. Intravenously applied sildenafil could be demonstrated to reduce PAP and pulmonary vasculature resistance (PVR) significantly. And after 3 months of oral sildenafil, the mean PAP has decreased from 30.2+/-5.5 mmHg (range: 24-39 mmHg) to 24.6+/-4.2 mmHg (range: 20-30 mmHg) (p=0.01). The PVR has decreased from 401+/-108 dyn s cm(-5) (range: 266-558 dyn s cm(-5)) to 264+/-52 dyn s cm(-5) (range: 204-333 dyn s cm(-5)) (p<0.05). Physical conditions improved: the 6-min walk distance increased from 351+/-49 to 433+/-52 m. In conclusion, in six patients suffering from severe COPD we could demonstrate significantly improved hemodynamic parameters after 50 mg sildenafil intravenous application. And after 3 months of oral sildenafil, walking distance in the 6 MWT increased significantly as well as hemodynamic parameters in the five patients who had accepted a second right heart catheterization.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Cardiac Catheterization; Exercise Test; Female; Forced Expiratory Volume; Hemodynamics; Humans; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Pulmonary Circulation; Pulmonary Disease, Chronic Obstructive; Purines; Sildenafil Citrate; Sulfones; Vascular Resistance; Walking

Sildenafil offers potential to treat patients with pulmonary hypertension by selectively inhibiting phosphodiesterase type five pathways in the lung. It is recommended for selected patients with pulmonary arterial hypertension, but its role in the management of pulmonary hypertension associated with parenchymal lung disease is unclear.. Seven patients (68-86 years) with end stage chronic obstructive pulmonary disease (COPD, 4) and idiopathic pulmonary fibrosis (IPF, 3) were referred to our unit. All patients had a long-term history of chronic lung disease and were on maximal appropriate therapy prescribed by their referring pulmonologist. Thromboembolic disease was excluded by pulmonary angiography and all patients had had high resolution thoracic CT scan. At assessment right heart catheterisation, 2D echocardiography and 6-min walk test were performed prior to commencement of sildenafil 50mg tds. Their medication was otherwise unchanged. After 8 weeks treatment, right heart catheterisation, 2D echocardiography and 6-min walk test were repeated.. The pulmonary vascular resistance was reduced in six patients (from 13, 3, 3, 6.5, 3.5 and 10.5 wood units to 9.7, 2.5, 2.8, 4.4, 2.5 and 5.4 wood units, respectively). Six-minute walk test increased in six patients (from 110 m, 210 m, 80 m, 30 m, 210 m and 80 m to 130 m, 312 m, 120 m, 82 m, 244 m and 100 m, respectively). One patient with COPD did not demonstrate a favourable response although their cardiac output increased on sildenafil therapy. 2D echocardiography showed a reduction in estimated PA pressure in six patients with an improvement in right ventricular systolic function in two COPD patients.. Our results suggest that sildenafil may have a role for selected patients with COPD and IPF who have pulmonary hypertension.

Topics: Aged; Aged, 80 and over; Cardiac Catheterization; Echocardiography; Exercise Test; Female; Humans; Hypertension, Pulmonary; Male; Phosphodiesterase Inhibitors; Piperazines; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Walking

Topics: Adult; Blood Pressure; Bronchi; Cardiovascular Diseases; Endothelium; Heart Ventricles; Humans; Male; Pilot Projects; Piperazines; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome; Ultrasonography; Vasodilator Agents

Topics: Bosentan; Humans; Hypertension, Pulmonary; Idiopathic Pulmonary Fibrosis; Insurance Coverage; Japan; Phenylpropionates; Prevalence; Prognosis; Pulmonary Disease, Chronic Obstructive; Pyrazoles; Pyridazines; Pyrimidines; Sildenafil Citrate; Sulfonamides; Treatment Outcome; Universal Health Insurance

Sildenafil improves the 6-min walking distance in patients with idiopathic pulmonary fibrosis (IPF) and right-sided ventricular systolic dysfunction.We analysed the previously unexplored role of sildenafil on vasoconstriction and remodelling of pulmonary arteries from patients with IPF and pulmonary hypertension (PH) ex vivo Pulmonary arteries from 18 donors without lung disease, nine IPF, eight PH+IPF and four PH patients were isolated to measure vasodilator and anti-contractile effects of sildenafil in isometric organ bath. Ventilation/perfusion was explored in an animal model of bleomycin lung fibrosis.Sildenafil relaxed serotonin (5-HT) pre-contracted pulmonary arteries in healthy donors and IPF patients and, to a lesser extent, in PH+IPF and PH. Sildenafil inhibited 5-HT dose-response contraction curve mainly in PH+IPF and PH, but not in healthy donors. Sildenafil did not impair the ventilation/perfusion mismatching induced by bleomycin. Pulmonary arteries from PH+IPF patients showed a marked expression of phosphodiesterse-5 and extracellular matrix components. Sildenafil inhibited pulmonary artery endothelial and smooth muscle cell to mesenchymal transition by inhibition of extracellular regulated kinases 1 and 2 (ERK1/2) and SMAD3 phosphorylation.These results suggest an absence of direct relaxant effect and a prominent anti-contractile and anti-remodelling role of sildenafil in PH+IPF pulmonary arteries that could explain the beneficial effects of sildenafil in IPF with PH phenotype.

Topics: Animals; Bleomycin; Disease Models, Animal; Endothelium, Vascular; Extracellular Matrix; Fibroblasts; Humans; Hypertension, Pulmonary; Lung; Male; Myocytes, Smooth Muscle; Myofibroblasts; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Rats; Rats, Wistar; Serotonin; Signal Transduction; Sildenafil Citrate; Transforming Growth Factor beta1; Vasoconstriction; Vasodilator Agents

Sildenafil, a phosphodiesterase-5 inhibitor used to treat pulmonary hypertension, may have effects on pulmonary vessel structure and function. We evaluated the effects of sildenafil in a cigarette smoke (CS)-exposed model of chronic obstructive pulmonary disease (COPD).42 guinea-pigs were exposed to cigarette smoke or sham-exposed and treated with sildenafil or vehicle for 12 weeks, divided into four groups. Assessments included respiratory resistance, pulmonary artery pressure (PAP), right ventricle (RV) hypertrophy, endothelial function of the pulmonary artery and lung vessel and parenchymal morphometry.CS-exposed animals showed increased PAP, RV hypertrophy, raised respiratory resistance, airspace enlargement and intrapulmonary vessel remodelling. CS exposure also produced wall thickening, increased contractility and endothelial dysfunction in the main pulmonary artery. CS-exposed animals treated with sildenafil showed lower PAP and a trend to less RV hypertrophy than CS-exposed only animals. Furthermore, sildenafil preserved the intrapulmonary vessel density and attenuated the airspace enlargement induced by CS. No differences in gas exchange, respiratory resistance, endothelial function and vessel remodelling were observed.We conclude that in this experimental model of COPD, sildenafil prevents the development of pulmonary hypertension and contributes to preserve the parenchymal and vascular integrity, reinforcing the notion that the nitric oxide-cyclic guanosine monophosphate axis is perturbed by CS exposure.

Topics: Animals; Disease Models, Animal; Guinea Pigs; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Male; Phosphodiesterase 5 Inhibitors; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Sildenafil Citrate; Tobacco Smoke Pollution

There is no recommendation for treating pulmonary hypertension (PH) when associated with chronic obstructive pulmonary disease (COPD).. To evaluate the effect of PH-specific therapy in patients with COPD.. All successive patients with severe PH [mean pulmonary arterial pressure (mPAP) ≥35 mm Hg] and COPD, who received specific PH medication and who underwent right heart catheterization at baseline and after 3-12 months of treatment, were analyzed from a prospective database.. Twenty-six patients were included with a median follow-up of 14 months. Mean forced expiratory volume in 1 s was 57 ± 20% of predicted, and mean forced expiratory volume in 1 s/forced vital capacity was 47 ± 12%. Dyspnea was New York Health Association classification stage (NYHA) II in 15%, NYHA III in 81% and NYHA IV in 4%. First-line treatments were endothelin receptor antagonists in 11 patients, phosphodiesterase-5 inhibitors in 11 patients, calcium blocker in 1 patient, combination therapy in 3 patients including 2 with a prostanoid. After 6 ± 3 months, pulmonary vascular resistance decreased from 8.5 ± 3 to 6.6 ± 2 Wood units (p < 0.001), with significant improvement of cardiac index from 2.44 ± 0.43 to 2.68 ± 0.63 liters × min × m-2 (p = 0.015) and mPAP from 48 ± 9 to 42 ± 10 mm Hg (p = 0.008). There was no significant difference in dyspnea, 6-min walking distance, echocardiographic parameters or N-terminal pro-brain natriuretic peptide levels. There was no significant difference in arterial oxygen saturation after 3-12 months of treatment.. Specific PH medications may improve hemodynamic parameters in COPD patients with severe PH. Appropriate prospective randomized studies are needed to evaluate the potential long-term clinical benefit of treatment.

Topics: Aged; Bosentan; Cohort Studies; Comorbidity; Female; Follow-Up Studies; France; Hemodynamics; Hospitals, University; Humans; Hypertension, Pulmonary; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Severity of Illness Index; Sildenafil Citrate; Statistics, Nonparametric; Sulfonamides; Treatment Outcome; Vascular Resistance; Vasodilator Agents

Recent imaging studies demonstrated the usefulness of quantitative computed tomographic (CT) analysis assessing pulmonary hypertension (PH) in patients with chronic obstructive lung disease (COPD-PH). The aim of this study was to investigate whether it would be also valuable for predicting and evaluating the effect of pulmonary vasodilators in patients with COPD-PH.. We analyzed a correlation between the extent of cystic destruction (LAA%) and total cross-sectional areas of small pulmonary vessels less than 5 mm(2) (%CSA <5) in many CT slices from each of four COPD-PH patients before and after the initiation of pulmonary vasodilator. To evaluate those generalized data from patients with COPD, we evaluated multiple slices from 42 patients whose PH was not clinically suspicious. We also selected five PH patients with idiopathic interstitial pneumonia (IIP-PH) and analyzed serial changes of pulmonary artery enlargement (PA:A ratio).. In 42 COPD patients without PH, LAA% had a statistically significant negative correlation with %CSA <5. However, three of four COPD-PH patients manifested no such correlation. In two patients, clinical findings were dramatically improved after the initiation of pulmonary vasodilator. Notably, LAA% and %CSA <5 in those patients correlated significantly after its treatment. In COPD-PH, the PA:A ratio was significantly decreased after the initiation of pulmonary vasodilator therapy (1.25 ± 0.13 vs. 1.13 ± 0.11, p = 0.019), but not in IIP-PH.. Our study demonstrates that the use of quantitative CT analysis is a plausible and beneficial tool for predicting and evaluating the effect of pulmonary vasodilators in patients with COPD-PH.

Topics: Aged; Bosentan; Endothelin Receptor Antagonists; Exercise Test; Female; Forced Expiratory Volume; Humans; Hypertension, Pulmonary; Male; Middle Aged; Pulmonary Artery; Pulmonary Diffusing Capacity; Pulmonary Disease, Chronic Obstructive; Pulmonary Fibrosis; Sildenafil Citrate; Sulfonamides; Tadalafil; Tomography, X-Ray Computed; Vasodilator Agents; Vital Capacity

Topics: Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Male; Piperazines; Pulmonary Disease, Chronic Obstructive; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Exercise Test; Female; Humans; Male; Oxygen Consumption; Piperazines; Pulmonary Disease, Chronic Obstructive; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Comorbidity; Dose-Response Relationship, Drug; Exercise Test; Exercise Tolerance; Hemodynamics; Humans; Hypertension, Pulmonary; Piperazines; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Purines; Severity of Illness Index; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Humans; Hypertension, Pulmonary; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Preoperative Care; Pulmonary Disease, Chronic Obstructive; Purines; Sildenafil Citrate; Sulfones

Topics: Anti-Anxiety Agents; Attention Deficit and Disruptive Behavior Disorders; Child; Comorbidity; Diagnosis, Differential; Dose-Response Relationship, Drug; Down Syndrome; Heart Defects, Congenital; Hospitalization; Humans; Hypertension, Pulmonary; Lorazepam; Male; Oxygen Inhalation Therapy; Piperazines; Pulmonary Disease, Chronic Obstructive; Purines; Risk Factors; Sildenafil Citrate; Sulfones; Vasodilator Agents

We report three cases of mechanically ventilated chronic obstructive pulmonary disease patients who were intubated due to an exacerbation of their disease and who presented with repeated spontaneous breathing trial failures. Patients were given 50 mg of sildenafil through the nasogastric tube, under close monitoring of haemodynamic and ventilatory parameters. After sildenafil, pulmonary artery pressure, pulmonary artery occlusion pressure, the respiratory frequency to tidal volume ratio and the P(a)CO2-P(ET)CO2 (arterial minus end-tidal carbon dioxide pressure) decreased. Cardiac output increased in two of the patients, while all of them were successfully extubated. This is the first report of successful extubation after sildenafil use.

Topics: Aged; Blood Gas Analysis; Humans; Male; Middle Aged; Piperazines; Pulmonary Disease, Chronic Obstructive; Purines; Respiratory Function Tests; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents; Ventilator Weaning

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Humans; Hypertension, Pulmonary; Patient Selection; Phosphodiesterase Inhibitors; Piperazines; Pulmonary Disease, Chronic Obstructive; Purines; Sildenafil Citrate; Sulfones

Beta2-adrenoceptor agonists are widely used in the treatment of pulmonary diseases. We have investigated the relaxant and anti-inflammatory activities of NCX-950 (alpha'-[[(1,1-dimethylethy)amino]methyl]-4-hydroxy-1,3-benzenedimethanol nitrate) (a nitric oxide-releasing salbutamol) in human isolated bronchi and on lipopolysaccharide (LPS)-induced acute airway inflammation in mice. NCX-950 (10(-8)-10(-5) M) elicited a relaxation of human isolated bronchi moderately higher than salbutamol, which was reduced by a beta-adrenergic blocking drug, propranolol, but not by an inhibitor of guanylate cyclase, ODQ (1H-[1,2,4]oxadiazolo[4,3-] quinolaxin-1-one). The treatment of mice with NCX-950 (1, 10, and 100 microM aerosol) markedly inhibited the neutrophil influx induced by LPS aerosol in bronchoalveolar lavage (BAL) fluid, whereas salbutamol at equimolar doses elicited a moderate inhibition. Pretreatment of mice with NCX-950 (100 microM) also significantly reduced tumor necrosis factor-alpha, interleukin-6 (IL-6), transforming growth factor-beta, and matrix metalloproteinase-9 release in BAL fluid, whereas salbutamol was ineffective. Propranolol, but not ODQ, suppressed the inhibitory activity of NCX-950 on neutrophil influx and IL-6 release in BAL fluids. A nitric oxide-releasing sildenafil NCX-911 [(5-[2-ethoxy-5-(4-methylpiperidinylsulfonyl)phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one nitrate)], but not sildenafil (100 microM) also reduced the neutrophil influx following LPS exposure in mice. This study reported that NCX-950 elicits potent relaxant and anti-inflammatory activities compared with salbutamol, and these effects may be mainly due to the activation of the beta2-adrenoceptor rather than the cGMP pathway.

Topics: Albuterol; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage; Bronchodilator Agents; Cell Movement; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Humans; Interleukin-6; Lipopolysaccharides; Male; Metalloproteases; Mice; Mice, Inbred BALB C; Nitric Oxide; Nitric Oxide Donors; Piperazines; Propranolol; Pulmonary Disease, Chronic Obstructive; Purines; Sildenafil Citrate; Sulfones

Topics: Bronchodilator Agents; Cholinergic Antagonists; Erectile Dysfunction; Female; Humans; Male; Parasympatholytics; Phosphodiesterase Inhibitors; Physician-Patient Relations; Piperazines; Pulmonary Disease, Chronic Obstructive; Purines; Risk Factors; Scopolamine Derivatives; Sildenafil Citrate; Sulfones; Time Factors; Tiotropium Bromide; Vasodilator Agents