Nitric Oxide In Acute Lung Injury Research Articles

Nitric Oxide Mediates Acute Lung Injury Caused by Fat Embolism in Isolated Rat’s Lungs

The involvement of nitric oxide (NO) in acute lung injury (ALI) induced by fat embolism (FE) has not been investigated. The present study elucidated the role of NO in ALI because of FE. FE was produced by introduction of fatty acid (corn oil micelles) into the isolated rat's lungs. Nonselective NO synthase (NOS) and selective inducible NOS (iNOS) inhibitors, N-nitro-l-arginine methyl ester (l-NAME) and l-N(1-iminoethyl)-lysine (l-Nil) as well as NO donors, sodium nitroprusside (SNP), and S-nitroso-N-acetylpenicillamine (SNAP) at a dose of 10 mol/L were given 60 minutes before FE. There were six groups of isolated lungs randomly assigned to receive vehicle (physiologic saline solution), FE, FE with pretreatment of l-NAME, l-Nil, SNP, or SNAP. Each group was observed for 4 hours. FE significantly increased the lung weight changes, pulmonary arterial pressure, and microvascular permeability. The concentration of nitrate or nitrite, methyl guanidine, tumor necrosis factor-alpha, and interleukin-1beta was significantly elevated after FE. Hisotopathologic examination revealed lung edema with multiple fatty droplets in lung tissue. Pretreatment with l-NAME or l-Nil attenuated, whereas SNP or SNAP exacerbated most of the FE-induced changes. Addition of NO donors (SNP or SNAP) into the isolated lungs did not produce significant changes in the lungs, suggesting that NO donation alone without FE does not exerts harmful effect. Our results suggest that NO production through the iNOS isoform plays a detrimental role in the FE-induced ALI. Free radical and proinflammatory cytokines may also be involved in the pathogenesis of ALI because of FE.

The effects of nitric oxide in acute lung injury

Acute lung injury (ALI) is a common clinical problem associated with significant morbidity and mortality. Ongoing clinical and basic research and a greater understanding of the pathophysiology of ALI have not been translated into new anti-inflammatory therapeutic options for patients with ALI, or into a significant improvement in the outcome of ALI. In both animal models and humans with ALI, there is increased endogenous production of nitric oxide (NO) due to enhanced expression and activity of inducible NO synthase (iNOS). This increased presence of iNOS and NO in ALI contributes importantly to the pathophysiology of ALI. However, inhibition of total NO production or selective inhibition of iNOS has not been effective in the treatment of ALI. We have recently suggested that there may be differential effects of NO derived from different cell populations in ALI. This concept of cell-source-specific effects of NO in ALI has potential therapeutic relevance, as targeted iNOS inhibition specifically to key individual cells may be an effective therapeutic approach in patients with ALI. In this paper, we will explore the potential role for endogenous iNOS-derived NO in ALI. We will review the evidence for increased iNOS expression and NO production, the effects of non-selective NOS inhibition, the effects of selective inhibition or deficiency of iNOS, and this concept of cell-source-specific effects of iNOS in both animal models and human ALI.

Nitric Oxide Potentiates Acute Lung Injury in an Isolated Rabbit Lung Model

Background. The effect of inhaled nitric oxide (NO) treatment on pulmonary function in the setting of adult respiratory distress syndrome is controversial. We examined the effect of inhaled NO on pulmonary function in an isolated rabbit lung model of oleic acid (OA)-induced acute lung injury. We hypothesized that NO would decrease pulmonary artery pressure and improve oxygenation. Methods. Rabbit heart-lung blocks were isolated, flushed in vivo, harvested, and immediately perfused with whole blood and ventilated with 50% oxygen (O 2). Pulmonary artery pressure was determined every 15 seconds for 60 minutes of perfusion. Oxygenation was determined by blood gas analysis of pulmonary venous effluent at 0, 20, 40, and 60 minutes after initiation of OA infusion. Rabbits were randomized into four study groups: saline control; OA control, which received a 20-minute infusion of 50% OA/ethanol solution; NO treatment (20 ppm NO inhaled before OA infusion); and NO control, which underwent NO (20 ppm) pretreatment, followed by saline infusion. Pulmonary artery pressure, oxygenation (arteriovenous O 2 difference), compliance, and wet/dry lung weight were determined. Results. Pretreatment with NO caused significant increases in pulmonary artery pressure (NO treatment versus NO control and saline control; no significant difference between NO treatment group and OA control group), and did not improve oxygenation in our model. Conclusions. Contrary to our hypothesis, pretreatment with NO potentiates acute lung injury in our isolated lung model. There was significant exacerbation of pulmonary hypertension and no improvement in oxygenation. Further investigation of the possible deleterious effects of NO in acute lung injury are needed, especially in the early acute phases of this process.