Edvard Terrence Weitzberg

BackgroundNitric oxide (NO) is a pluripotent signaling molecule involved in numerous physiological processes. This tiny gas is classically produced by specific NO synthases, but we and others have discovered an alternative pathway for NO generation, namely by serial reduction of the inorganic anions nitrate (NO3-) and nitrite (NO2-). This nitrate-nitrite-NO pathway can be stimulated by administration of these anions, thereby boosting NO bioavailability, which is negatively affected in many diseases and in the Intensive Care Unit (ICU) setting.AimsIn a series of proof-of-concept studies we will explore the therapeutic effects of nitrate and nitrite and the diagnostic potential of measuring exhaled NO in anesthesia and intensive care.Project planIn ICU patients we will first explore the compartmental distribution and metabolic fate of administered nitrite.In patients with Adult Respiratory Stress Syndrome we will investigate the potential pulmonary benefit of inhaled nitrite.We will study the effects of preoperative nitrate in major surgery with focus on bleeding, inflammation, and endothelial function.Finally, we will investigate if exhaled NO can be an early non-invasive biomarker of ventilator-associated pneumonia.SignificanceNitric oxide bioavailability is threatened in patients subjected to major surgery and intensive care. Stimulation of the nitrate-nitrite-NO pathway by the simple anions nitrate and nitrite may prove to be of therapeutic benefit in these patient groups.