sildenafil-citrate and Pulmonary-Edema

Swimming-induced pulmonary edema (SIPE) occurs during swimming or scuba diving, often in young individuals with no predisposing conditions, and its pathophysiology is poorly understood. This study tested the hypothesis that pulmonary artery and pulmonary artery wedge pressures are higher in SIPE-susceptible individuals during submerged exercise than in the general population and are reduced by sildenafil.. Ten study subjects with a history of SIPE (mean age, 41.6 years) and 20 control subjects (mean age, 36.2 years) were instrumented with radial artery and pulmonary artery catheters and performed moderate cycle ergometer exercise for 6 to 7 minutes while submersed in 20°C water. SIPE-susceptible subjects repeated the exercise 150 minutes after oral administration of 50 mg sildenafil. Work rate and mean arterial pressure during exercise were similar in controls and SIPE-susceptible subjects. Average o2 and cardiac output in controls and SIPE-susceptible subjects were: o2 2.42 L·min(-1) versus 1.95 L·min(-1), P=0.2; and cardiac output 17.9 L·min(-1) versus 13.8 L·min(-1), P=0.01. Accounting for differences in cardiac output between groups, mean pulmonary artery pressure at cardiac output=13.8 L·min(-1) was 22.5 mm Hg in controls versus 34.0 mm Hg in SIPE-susceptible subjects (P=0.004), and the corresponding pulmonary artery wedge pressure was 11.0 mm Hg versus 18.8 mm Hg (P=0.028). After sildenafil, there were no statistically significant differences in mean pulmonary artery pressure or pulmonary artery wedge pressure between SIPE-susceptible subjects and controls.. These observations confirm that SIPE is a form of hemodynamic pulmonary edema. The reduction in pulmonary vascular pressures after sildenafil with no adverse effect on exercise hemodynamics suggests that it may be useful in SIPE prevention.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00815646.

Topics: Adult; Cardiac Output; Cold Temperature; Exercise Test; Female; Humans; Male; Middle Aged; Oxygen Consumption; Pulmonary Edema; Pulmonary Wedge Pressure; Risk Reduction Behavior; Sildenafil Citrate; Swimming; Vasodilator Agents

Swimming-induced pulmonary edema (SIPE) occurs during swimming and scuba diving, usually in cold water, in susceptible healthy individuals, especially military recruits and triathletes. We have previously demonstrated that pulmonary artery (PA) pressure and PA wedge pressure are higher during immersed exercise in SIPE-susceptible individuals versus controls, confirming that SIPE is a form of hemodynamic pulmonary edema. Oral sildenafil 50 mg 1 h before immersed exercise reduced PA pressure and PA wedge pressure, suggesting that sildenafil may prevent SIPE. We present a case of a 46-yr-old female ultratriathlete with a history of at least five SIPE episodes. During a study of an exercise submerged in 20°C water, physiological parameters before and after sildenafil 50 mg orally were as follows: O2 consumption 1.75, 1.76 L·min; HR 129, 135 bpm; arterial pressure 189/88 (mean 121.5), 172/85 (mean 114.3) mm Hg; mean PA pressure 35.3, 28.8 mm Hg; and PA wedge pressure 25.3, 19.7 mm Hg. She has had no recurrences during 20 subsequent triathlons while taking 50 mg sildenafil before each swim. This case supports sildenafil as an effective prophylactic agent against SIPE during competitive surface swimming.

Topics: Female; Hemodynamics; Humans; Middle Aged; Pulmonary Edema; Pulmonary Wedge Pressure; Secondary Prevention; Sildenafil Citrate; Swimming; Vasodilator Agents

Topics: Female; Humans; Male; Pulmonary Edema; Risk Reduction Behavior; Sildenafil Citrate; Swimming

Topics: Humans; Hypertension, Pulmonary; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Piperazines; Pulmonary Edema; Pulmonary Veno-Occlusive Disease; Purines; Sildenafil Citrate; Sulfones; Ventricular Dysfunction, Left

To provide guidance to clinicians about best practices, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for the prevention and treatment of acute mountain sickness (AMS), high altitude cerebral edema (HACE), and high altitude pulmonary edema (HAPE). These guidelines present the main prophylactic and therapeutic modalities for each disorder and provide recommendations for their roles in disease management. Recommendations are graded based on the quality of supporting evidence and balance between the benefits and risks/burdens according to criteria put forth by the American College of Chest Physicians. The guidelines also provide suggested approaches to the prevention and management of each disorder that incorporate these recommendations.

Topics: Acetazolamide; Acute Disease; Albuterol; Altitude Sickness; Brain Edema; Carbolines; Dexamethasone; Humans; Mountaineering; Nifedipine; Piperazines; Pulmonary Edema; Purines; Salmeterol Xinafoate; Sildenafil Citrate; Societies; Sulfones; Tadalafil; Wilderness Medicine

This study was performed to delineate the kinin (receptor)-dependent pathways in the Indian red scorpion (Mesobuthus tamulus; MBT) venom-induced pulmonary oedema as well as the augmentation of cardio-pulmonary reflexes evoked by phenyldiguanide (PDG).. In urethane-anaesthetized adult rats, the effect of venom on the PDG reflex responses (blood pressure, heart rate and respiration rate) and the pulmonary water content was ascertained using various antagonists(des- Arg, B(1) receptor antagonist; Hoe 140, B(2) receptor antagonist; N(omega)-nitro-l-arginine methyl ester (l-NAME), nitric oxide (NO) synthase inhibitor; methylene blue, soluble guanylate cyclase inhibitor; and glibenclamide, K(+)(ATP) channel blocker). The effect of phosphodiesterase V inhibitor (sildenafil citrate) on the reflex response and the pulmonary water content was also examined and compared with venom-induced responses.. Intravenous injection of PDG (10 microg kg(-1)) evoked apnoea, bradycardia and hypotension lasting >60 s. Exposure to MBT venom (100 microg kg(-1)) for 30 min augmented the PDG reflex responses by two times and increased the pulmonary water content, significantly. Hoe 140 blocked the venom-induced responses (augmentation of PDG reflex and increased pulmonary water content) whereas des-Arg did not. l-NAME, methylene blue or glibenclamide also blocked the venom-induced responses. Furthermore, sildenafil citrate (that increases cGMP levels) produced augmentation of PDG reflex response and increased the pulmonary water content as seen with venom.. The results indicate that venom-induced responses involve B(2) kinin receptors via the NO-dependent guanylate cyclase-cGMP pathway involving K(+)(ATP) channels.

Topics: Adrenergic beta-Antagonists; Animals; Biguanides; Bradykinin; Bradykinin B2 Receptor Antagonists; Enzyme Inhibitors; Glyburide; Guanosine Monophosphate; Heart; Hypoglycemic Agents; Lung; Male; Metabolic Networks and Pathways; Methylene Blue; NG-Nitroarginine Methyl Ester; Nitric Oxide; Piperazines; Pulmonary Edema; Purines; Rats; Receptor, Bradykinin B2; Reflex; Scorpion Venoms; Scorpions; Serotonin Receptor Agonists; Sildenafil Citrate; Sulfones

Climbers who have suffered a previous episode of high altitude pulmonary edema (HAPE) are at significantly increased risk of developing it again on return to high altitude. In spite of the high mortality associated with HAPE, some climbers are willing to take this risk in order to summit the tallest mountains in the world. This is a case report of a climber who suffered an episode of HAPE partway up Mount Everest. He was determined to complete his summit attempt that same climbing season, which would involve a return to extreme altitude less than 3 weeks following recovery. Based on experimental evidence suggesting that sildenafil, salmeterol, and acetazolamide may have therapeutic value for both the prevention and treatment of HAPE, he used these medications for secondary prevention. He was able to successfully reach the summit of Mount Everest and return to base camp without any evidence of recurrence of pulmonary edema. This provides clinical evidence that medication can be used to increase the safety margin for HAPE-susceptible individuals traveling to extremely high altitudes.

Topics: Acetazolamide; Adult; Albuterol; Altitude; Bronchodilator Agents; Diuretics; Humans; Male; Mountaineering; Piperazines; Pulmonary Edema; Purines; Salmeterol Xinafoate; Secondary Prevention; Sildenafil Citrate; Sulfones; Vasodilator Agents

Topics: Bosentan; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Middle Aged; Piperazines; Pulmonary Edema; Pulmonary Medicine; Pulmonary Veno-Occlusive Disease; Purines; Risk; Sildenafil Citrate; Sulfonamides; Sulfones; Tomography, X-Ray Computed; Treatment Outcome

Pulmonary veno-occlusive disease (PVOD) is a disorder which causes progressive pulmonary hypertension, usually presenting with worsening dyspnoea and right heart failure. Pulmonary oedema induced by pulmonary vasodilator therapy to reduce pulmonary arterial pressure has been well described in PVOD, but here we describe a case of PVOD presenting with recurrent episodes of acute non-cardiogenic pulmonary oedema, in the absence of significant pulmonary hypertension. Concern over the risk of precipitating pulmonary oedema led us to use inhaled nitric oxide to predict the safety and efficacy of sildenafil.

Topics: Adult; Bronchodilator Agents; Dyspnea; Humans; Male; Nitric Oxide; Piperazines; Pulmonary Edema; Pulmonary Veno-Occlusive Disease; Purines; Recurrence; Sildenafil Citrate; Sulfones; Tomography, X-Ray Computed; Vasodilator Agents

We tested the hypothesis that chronic treatment with sildenafil attenuates myocardial infarction (MI)-induced heart failure. Sildenafil has potent protective effects against necrosis and apoptosis following ischemia-reperfusion in the intact heart and cardiomyocytes. ICR mice underwent MI by left anterior descending coronary artery ligation and were treated with sildenafil (0.71 mg/kg bid) or saline for 4 wk. Infarct size (IS) was measured 24 h postinfarction, and apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Left ventricular end-diastolic diameter (LVEDD) and fractional shortening (FS) were measured by echocardiography. Sildenafil reduced IS (40.0 +/- 4.6%) compared with that in saline (69.6 +/- 4.1%, P < 0.05). NG-nitro-l-arginine methyl ester, a nitric oxide synthase (NOS) inhibitor (15 mg/kg bid), blocked the protective effect of sildenafil (IS, 60.2 +/- 1.6%, P < 0.05 vs. sildenafil). Western blot analysis revealed a significant increase in endothelial NOS/inducible NOS proteins 24 h post-MI after treatment with sildenafil versus saline. Apoptosis decreased from 2.4 +/- 0.3% with saline to 1.2 +/- 0.1% with sildenafil (P < 0.05) on day 7 and from 2.0 +/- 0.2% with saline to 1.2 +/- 0.1% with sildenafil on day 28 (P < 0.05), which was associated with an early increase in the Bcl-2-to-Bax ratio. LVEDD increased from baseline value of 3.6 +/- 0.1 to 5.2 +/- 0.2 and to 5.5 +/- 0.1 mm on days 7 and 28, respectively, with saline (P < 0.05) but was attenuated to 4.4 +/- 0.2 and 4.4 +/- 0.1 mm following sildenafil treatment on days 7 and 28, respectively (P > 0.05 vs. baseline). FS significantly improved post-MI with sildenafil. A marked decline in cardiac hypertrophy was observed with sildenafil, which paralleled a reduction in pulmonary edema. Survival rate was lower with saline (36%) compared with sildenafil (93%, P < 0.05). Sildenafil attenuates ischemic cardiomyopathy in mice by limiting necrosis and apoptosis and by preserving left ventricular function possibly through a nitric oxide-dependent pathway.

Topics: Animals; Apoptosis; Blotting, Western; Cardiomegaly; Cardiomyopathy, Restrictive; Coronary Vessels; Echocardiography, Doppler; Enzyme Inhibitors; In Situ Nick-End Labeling; Ligation; Male; Mice; Mice, Inbred ICR; Myocardial Infarction; Necrosis; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Piperazines; Pulmonary Edema; Purines; Sildenafil Citrate; Sulfones; Survival Analysis; Vasodilator Agents; Ventricular Function, Left; Ventricular Remodeling

Improvement of preservation is still a major research objective in lung transplantation. The effects of phosphodiesterase-5 (PDE-5) inhibitors during procurement are still not clear. It was the aim of this study to investigate the effect of sildenafil on post-transplanted lung function in a porcine model using different application procedures.. In control group lungs were flushed with buffered low-potassium dextran (LPD) solution (I) and compared to LPD solution with supplementation of 0.15 mg/kg body weight (BW) sildenafil (II), whereas in a third group 0.15 mg/kg BW sildenafil was administered intravenously 20 min prior to LPD flushing (III). All grafts were stored for 24 h at 4-6 degrees C. Hemodynamics and blood gases were monitored until 6 h after reperfusion. Lung tissue was taken for wet/dry ratio assessment.. All animals of groups I and III survived the entire observation period in contrast to four animals of group II which died within 4 h after reperfusion due to severe reperfusion injury. Group II showed a lower mean PAP and a reduced pulmonary vascular resistance (PVR) throughout the observation period, but did not reach significance due to low number of surviving animals. Group III achieved significantly improved PO2/FiO2 fraction at all timepoints and a significant reduced PVR [434+/-98 vs 594+/-184 dyn s cm(-5), II vs I; mean+/-SD, p<0.01] at 6 h. Wet/dry ratio was significantly higher in group II throughout the experiment.. Sildenafil allows for a better graft function after 24 h ischemia when given prior to standard flushing and preservation. This effect can be explained by a complete/homogenous preservation achieved by selective pulmonal vasodilatation. However, this effect seems to persist when sildenafil remains in the storage solution, leading to severe pulmonary edema.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Blood Pressure; Cyclic Nucleotide Phosphodiesterases, Type 5; Drug Evaluation, Preclinical; Extravascular Lung Water; Graft Survival; Lung Transplantation; Male; Organ Preservation; Phosphodiesterase Inhibitors; Piperazines; Pulmonary Artery; Pulmonary Edema; Purines; Reperfusion Injury; Sildenafil Citrate; Sulfones; Swine; Transplantation Conditioning; Vascular Resistance

High altitude pulmonary edema (HAPE) is the leading cause of death from altitude illness and rapid descent is often considered a life-saving foundation of therapy. Nevertheless, in the remote settings where HAPE often occurs, immediate descent sometimes places the victim and rescuers at risk. We treated 11 patients (7 Nepalese, 4 foreigners) for HAPE at the Himalayan Rescue Association clinic in Pheriche, Nepal (4240 m), from March 3 to May 14, 2006. Ten were admitted and primarily treated there. Seven of these (6 Nepalese, 1 foreigner) had serious to severe HAPE (Hultgren grades 3 or 4). Bed rest, oxygen, nifedipine, and acetazolamide were used for all patients. Sildenafil and salmeterol were used in most, but not all patients. The duration of stay was 31 +/- 16 h (range 12 to 48 h). Oxygen saturation was improved at discharge (84% +/- 1.7%) compared with admission (59% +/- 11%), as was ultrasound comet-tail score (11 +/- 4 at discharge vs. 33 +/- 8.6 at admission), a measure of pulmonary edema for which admission and discharge values were obtained in 7 patients. We conclude it is possible to treat even serious HAPE at 4240 m and discuss the significance of the predominance of Nepali patients seen in this series.

Topics: Acetazolamide; Adult; Albuterol; Altitude; Altitude Sickness; Bed Rest; Emergency Treatment; Female; Humans; Male; Middle Aged; Mountaineering; Nepal; Nifedipine; Oxygen Inhalation Therapy; Piperazines; Pulmonary Edema; Purines; Salmeterol Xinafoate; Sildenafil Citrate; Sulfones; Treatment Outcome; Vasodilator Agents

Topics: Altitude Sickness; Humans; Phosphodiesterase Inhibitors; Piperazines; Pulmonary Edema; Purines; Sildenafil Citrate; Sulfones

Topics: Female; Humans; Hypertension, Pulmonary; Middle Aged; Piperazines; Pulmonary Artery; Pulmonary Edema; Purines; Sildenafil Citrate; Sulfones; Vasodilator Agents

High-altitude pulmonary edema reflects a potentially life-threatening condition affecting susceptible persons in the second night after ascent to altitudes above 2500 m. Currently, nifedipine is the only pharmacological intervention approved for both, prevention and treatment of high-altitude pulmonary edema. We evaluated the application of the phosphodiesterase-V inhibitor sildenafil combined with the non-selective phosphodiesterase-inhibitor theophylline as preventive agents. In theory, the proposed regimen can impede the two main pathophysiological features of high-altitude pulmonary edema: the deleteriously high pulmonary artery pressure (sildenafil's task) on the one hand, and the activation of an inflammatory cascade (theophylline's task) on the other hand. We suggest that these orally applicable phosphodiesterase inhibitors might be useful in the prevention of high-altitude pulmonary edema.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Altitude Sickness; Cyclic Nucleotide Phosphodiesterases, Type 5; Humans; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Pulmonary Edema; Purines; Sildenafil Citrate; Sulfones; Theophylline