sildenafil-citrate and Respiratory-Distress-Syndrome

Acute respiratory distress syndrome, a diagnosis based on physiologic and radiological criteria, occurs commonly in critical care setting. A major challenge in evaluating therapies that may improve survival in ARDS is that it is not a single disease entity but, rather, numerous different diseases that result in endothelial injury, where the most obvious manifestation is within the lung resulting in pulmonary oedema. It has been shown that poor ventilatory technique that is injurious to the lungs can propagate systemic inflammatory response and adversely affect the mortality. The current data suggest that high tidal volumes with high plateau pressures are deleterious and a strategy of ventilation with lower tidal volumes and lower plateau pressure is associated with lower mortality. There may be a role for recruitment manoeuvres as well. Other forms of respiratory support still require further research. The present understanding of optimal ventilatory management and other adjunctive therapies are reviewed.

Topics: Administration, Inhalation; Child; Extracorporeal Membrane Oxygenation; Glucocorticoids; High-Frequency Ventilation; Humans; Liquid Ventilation; Nitric Oxide; Piperazines; Positive-Pressure Respiration; Prone Position; Pulmonary Surfactants; Pulmonary Ventilation; Purines; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory System Agents; Sildenafil Citrate; Sulfones; Tidal Volume; Vasodilator Agents

Pulmonary hypertension is a characteristic feature of acute respiratory distress syndrome (ARDS) and contributes to mortality. Administration of sildenafil in ambulatory patients with pulmonary hypertension improves oxygenation and ameliorates pulmonary hypertension. Our aim was to determine whether sildenafil is beneficial for patients with ARDS.. Prospective, open-label, multicenter, interventional cohort study.. Medical-surgical ICU of two university hospitals.. Ten consecutive patients meeting the NAECC criteria for ARDS.. A single dose of 50 mg sildenafil citrate administered via a nasogastric tube.. Administration of sildenafil in patients with ARDS decreased mean pulmonary arterial pressure from 25 to 22 mmHg (P = 0.022) and pulmonary artery occlusion pressure from 16 to 13 mmHg (P = 0.049). Systemic mean arterial pressures were markedly decreased from 81 to 75 mmHg (P = 0.005). Sildenafil did not improve pulmonary arterial oxygen tension, but resulted in a further increase in the shunt fraction.. Although sildenafil reduced pulmonary arterial pressures during ARDS, the increased shunt fraction and decreased arterial oxygenation render it unsuitable for the treatment of patients with ARDS.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Aged; Cohort Studies; Female; Humans; Hypertension, Pulmonary; Intensive Care Units; Male; Middle Aged; Oxygen; Oxygen Consumption; Piperazines; Prospective Studies; Pulmonary Artery; Purines; Respiratory Distress Syndrome; Sildenafil Citrate; Sulfones; Vasodilator Agents

The effects of LASSBio596, a phosphodiesterase type-4 and -5 inhibitor, were tested in Escherichia coli lipopolysaccharide (LPS)-induced acute lung injury. Twenty-four BALB/c mice were randomly divided into four groups. In the control group, saline (0.05 mL) was injected intratracheally (i.t.). The LPS group received LPS (10 microg i.t., 0.05 mL). In the LASSBio596 groups, LASSBio596 (10 mg x kg(-1), 0.2 mL) was injected intraperitoneally 1 h before or 6 h after LPS administration. After 24 h, in vivo (lung resistive and viscoelastic pressures, and static and dynamic elastances) and in vitro (tissue resistance, elastance and hysteresivity) pulmonary mechanics, lung morphometry and collagenous fibre content were computed. Neutrophils and tumour necrosis factor (TNF)-alpha levels were evaluated in the bronchoalveolar lavage fluid. LASSBio596 prevented the changes in lung mechanics, and inhibited neutrophilic recruitment, TNF-alpha release, bronchoconstriction, alveolar collapse and the increment of collagen fibre content induced by LPS, independently of the moment of injection. In conclusion, LASSBio596 modulated the lung inflammatory process and had the potential to block fibroproliferation. Thus, agents that inhibit phosphodiesterase 4 and 5 simultaneously may be a useful adjunct therapy for acute lung injury.

Topics: Analysis of Variance; Animals; Bronchoalveolar Lavage Fluid; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Neutrophils; Phosphodiesterase Inhibitors; Piperazines; Purines; Respiratory Distress Syndrome; Respiratory Function Tests; Respiratory Mechanics; Sildenafil Citrate; Statistics, Nonparametric; Sulfones; Thalidomide; Tumor Necrosis Factor-alpha

Topics: COVID-19; Extracorporeal Membrane Oxygenation; Humans; Respiratory Distress Syndrome; Sildenafil Citrate

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Humans; Hypertension, Pulmonary; Piperazines; Purines; Respiratory Distress Syndrome; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Humans; Piperazines; Pulmonary Artery; Purines; Respiratory Distress Syndrome; Sildenafil Citrate; Sulfones; Vascular Resistance; Vasodilator Agents

Inhalation of nitric oxide (NO) and inhibition of phosphodiesterase type 5 (PDE5) selectively dilate the pulmonary circulation in patients with acute lung injury (ALI) associated with pulmonary hypertension. PDE5 inhibitors administered at doses that decrease pulmonary artery pressures have been shown to worsen arterial oxygenation. We investigated the efficacy of doses of PDE5 inhibitors that do not reduce pulmonary artery pressure alone (subthreshold doses) to improve the response to inhaled NO in an animal model of ALI.. Adult Sprague-Dawley rats were pre-treated with 0.5 mg/kg Escherichia coli 0111:B4 endotoxin and 16 to 18 h later, their lungs were isolated perfused and ventilated. The thromboxane mimetic U46619 was used to induce pulmonary hypertension. After the determination of subthreshold doses of two different PDE5 inhibitors, either 50 microg zaprinast or 10 ng sildenafil was added to the perfusate and the decrease of pulmonary artery pressure measured in the presence and absence of inhaled NO.. In the presence of 4 or 10 ppm NO, zaprinast (-1.6 +/- 0.4 and -2.9 +/- 0.6 mmHg, respectively) and sildenafil (-1.9 +/- 0.4 and -2.4 + 0.3 mmHg, respectively) improved responsiveness to inhaled NO compared to lungs from rats treated with LPS only (0.7 +/- 0.1 and -1.0 +/- 0.1 mmHg, respectively; P<0.05). Neither zaprinast nor sildenafil prolonged the pulmonary vasodilatory response to inhaled NO.. Subthreshold doses of PDE5 inhibitors improved responsiveness to inhaled NO. Combining inhaled NO with subthreshold doses of PDE5 inhibitors may offer a therapeutic strategy with minimal side-effects in ALI associated with pulmonary hypertension.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Administration, Inhalation; Animals; Bronchodilator Agents; Cyclic Nucleotide Phosphodiesterases, Type 5; Dose-Response Relationship, Drug; Drug Synergism; Endotoxemia; In Vitro Techniques; Nitric Oxide; Phosphodiesterase Inhibitors; Piperazines; Pulmonary Circulation; Pulmonary Wedge Pressure; Purines; Purinones; Rats; Respiratory Distress Syndrome; Sildenafil Citrate; Sulfones; Vasodilation

Post-pneumonectomy respiratory failure is a devastating complication of resection for lung cancer. As proven therapy is limited, we successfully employed a novel medication silfenadil that has been effective in the treatment of pulmonary hypertension.

Topics: Carcinoma, Bronchogenic; Female; Humans; Lung Neoplasms; Middle Aged; Nitric Oxide; Nitric Oxide Donors; Piperazines; Pneumonectomy; Purines; Respiratory Distress Syndrome; Respiratory Insufficiency; Sildenafil Citrate; Sulfones; Treatment Outcome

Topics: Antihypertensive Agents; Bosentan; Extracorporeal Membrane Oxygenation; Female; Humans; Middle Aged; Nitric Oxide; Phosphodiesterase Inhibitors; Piperazines; Purines; Respiratory Distress Syndrome; Sildenafil Citrate; Substance Withdrawal Syndrome; Sulfonamides; Sulfones; Vasodilator Agents; Ventilator Weaning

Impotence, a common problem especially among older men, can now be treated with Viagra, This oral pill, unlike previous approved treatments mostly involving local injections, does not directly cause penile erection, but increases response to sexual stimulation. It acts by enhancing the relaxant effects of nitric acid on smooth muscle, and thus increases blood flow to certain areas of the penis, leading to erection. It has been evaluated in many randomized trials and in all was more successful in inducing erection than placebos. The most common side-effects include headache, flushing and indigestion, but there have also been reports of fatalities. We describe a 75-year-old man who had an acute myocardial infraction in the past and who had maturity-onset diabetes and hypertension. In the week prior to admission he had a cardiac scan following a few weeks of exacerbation of anginal pain for which he had been taking nitrites. He took a Viagra pill without prescription or medical advice and 2 hours later, during intercourse with his wife, developed audible respiratory distress and lost consciousness. His wife started cardiac massage but not mouth-to-mouth breathing. The emergency team found ventricular fibrillation and gave 5 electrical shocks and amines and atropine. He remained unconscious, but his pulse returned and he was hospitalized. He then had several generalized convulsions treated with i.v. valium. 20 minutes after admission there was asystole and all attempts at resuscitation failed. Cardiovascular status must be considered prior to prescribing Viagra, and the associated risk evaluated.

Topics: Aged; Diabetes Mellitus, Type 2; Erectile Dysfunction; Fatal Outcome; Humans; Hypertension; Male; Phosphodiesterase Inhibitors; Piperazines; Purines; Respiratory Distress Syndrome; Sildenafil Citrate; Sulfones; Unconsciousness