Are sildenafil and theophylline effective in the prevention of high-altitude pulmonary edema?
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.
The Innsbruck Pulmonary Research Group, Department of Anesthesiology and Critical Care Medicine, TILAK General Hospital, Innsbruck, Austria. akleinsasser@ucsd.edu
Axel
A
Kleinsasser
A
A
Loeckinger
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000532:Altitude Sickness / Q000517:prevention & control*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006801:Humans; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D011654:Pulmonary Edema / Q000517:prevention & control*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D013806:Theophylline / Q000494:pharmacology / Q000627:therapeutic use*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D013806:Theophylline; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human