Effects of Nebulized Diethylenetetraamine-NONOate in a Mouse Model of Acute Pseudomonas aeruginosa Pneumonia
Bacterial pneumonia remains a common and important clinical problem. Despite effective antimicrobial therapy, pneumonia has significant morbidity and mortality, especially in hospitalized patients and in those patients with certain pathogens, such as Pseudomonas aeruginosa. Pneumonia is characterized by intrapulmonary bacterial proliferation, pulmonary edema, neutrophil infiltration, and parenchymal lung injury. Therapy targeted at these pathophysiologic features of pneumonia may be beneficial in the clinical management of patients with pneumonia. buy ventolin inhaler
Nitric oxide (NO) is a ubiquitous mammalian mediator with many homeostatic effects, such as vasodilation and immune modulation. Endogenous NO has been shown to have both proinflammatory and anti-inflammatory effects in various models of lung injury. Moreover, the antibacterial effects of NO also have been described.
The gaseous nature of NO and its recognized selective pulmonary vasodilatory effects have led to the clinical use of inhaled NO (iNO) in pulmonary hypertension and in acute lung injury. Furthermore, antibacterial and anti-inflammatory effects of iNO in various models of lung injury have been suggested. Continuous iNO therapy usually is restricted to patients who are intubated and ventilated with closed circuits because of concerns about health-care giver safety on exposure to ambient NO and its oxidative metabolite, NO2.
NONOates are synthetic adducts of NO and a nucleophile backbone that spontaneously and non-enzymatically release NO at predictable rates. Different NONOates are characterized by differences in half-life and the resulting rate of NO release. The intermittent inhalation of a nebulized NONOate solution may permit the continuous release of NO in the lower respiratory tract, which may avoid the technical complexities and potential risks of continuous iNO delivery.