European journal of medical research
-
Clinical Trial
Response to inhaled nitric oxide (NO) is not associated with changes of plasma cGMP levels in patients with acute lung injury.
A clinically relevant increase of PaO subset2 or decrease of pulmonary vascular resistance (PVR) upon inhalation of NO (iNO) does occur in only 60 to 80% of patients with acute lung injury. The mechanisms for divergent responses of different patients have not yet been fully elucidated. Since NO mediates its pulmonary effects by stimulating soluble guanylate cyclase, thereby increasing levels of cyclic guanosinemonophosphate (cGMP), we hypothesized that pulmonary cGMP production upon iNO might be suppressed in patients not responding to iNO treatment. ⋯ Inhalation of NO significantly stimulates soluble guanylate cyclase within the lungs in patients with acute lung injury. However, neither baseline cGMP nor its rise during treatment with inhaled NO can predict the clinical efficacy of iNO in humans. Furthermore, the fact that increased cGMP concentrations were detected during administration of iNO in mixed venous blood (i.e. pulmonary inflow) strongly suggest that the pharmacological effects of iNO are not fully selective for the lungs, but may also affect extrapulmonary organs.