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Title: Nitric oxide in the lung
Author: Cuthbertson, B. H.
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1997
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Aim: To study the role of NO in inflammatory and immune processes within the lung. Methods: 1. A study of the in-vitro response of human neutrophils and whole blood cultures to exogenous NO and superoxide donors with regard to interleukin-8 and elastase accumulation. 2. In a randomised controlled study of inhaled NO versus control in ALI the effects of inhaled NO on inflammatory and immune responses within the lung was studied. Results: 1. NO donors are seen to have varying effects on interleukin-8 accumulation from human neutrophils and on interleukin-8 and elastase accumulation from whole blood incubation. 2. Inhaled NO therapy is seen to reduce time to resolution of ALI but did not effect mortality. Leucocyte NOS activity was reduced in the inhaled NO group whilst plasma total nitrite and nitrate was seen to increase. Bronchoalveolar (BAL) fluid leukotriene levels at 72 hours were also demonstrated to increase with inhaled NO treatment. BAL fluid myeloperoxidase was demonstrated to be a outcome marker in ALI. There was no difference between BAL fluid IL-8, elastase and myeloperoxidase levels between groups. Discussion: These results demonstrate that NO has significant effects on neutrophil function in-vitro. Inhaled NO therapy also reduces time to resolution of ALI which may reduce morbidity and cost of ITU care. Although there was an increase in BAL leukotriene levels in the treatment group there was not a significant rise in other inflammatory markers suggesting that inhaled NO may not be causing a large alteration in inflammatory response within the lung in ALI. The regulation of NOS activity may explain the mechanism of rebound phenomena upon inhaled NO withdrawal. Increased plasma total nitrite and nitrate demonstrates the importance of this route to metabolism on the biological breakdown of inhaled NO.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available