Pulmonary Macrophage Inhibition and Inhaled Nitric Oxide Attenuate Lung Ischemia-Reperfusion Injury

Leo M. Gazoni, Curtis G. Tribble, Min Q. Zhao, Eric B. Unger, Robert A. Farrar, Peter I. Ellman, Lucas G. Fernandez, Victor E. Laubach, Irving L. Kron

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23 Scopus citations


Background: Lung ischemia-reperfusion injury (LIRI) is postulated to occur biphasically. Donor pulmonary macrophages mediate early injury, and neutrophil-dependent injury predominates in the later phase of LIRI. We hypothesized that the biphasic response to LIRI would be attenuated by the administration of gadolinium, a known pulmonary macrophage inhibitor, and inhaled nitric oxide (NO), a pulmonary vasodilator that also interferes with neutrophil chemotaxis. Methods: Using our isolated, ventilated, blood-perfused rabbit lung model, study groups (n = 10 per group) underwent two hours of reperfusion after 18 hours of cold ischemia (4°C). Lungs received gadolinium alone, or inhaled NO in the presence or absence of macrophage inhibition with gadolinium. Results: Compared with control animals, pulmonary macrophage inhibition with the concurrent administration of inhaled NO increased lung compliance (p < 0.01) and oxygenation (p = 0.03), while also decreasing pulmonary artery pressure (p < 0.01), myeloperoxidase content by 63% (p < 0.01), wet to dry ratios by 23% (p < 0.01), and lung tissue (p < 0.01) and bronchoalveolar lavage tumor necrosis factor-α (TNF-α) protein levels (p < 0.01). Conclusions: The severity of LIRI was most significantly reduced by the inhibition of pulmonary macrophages and the concomitant use of inhaled NO. Pulmonary macrophages, likely through the elaboration of proinflammatory cytokines such as TNF-α, not only cause early injury themselves but also prime cells such as neutrophils to injure lungs in the later stages of LIRI. The LIRI was effectively blunted by the reduction of macrophage-dependent injury by gadolinium while inhaled NO also attenuated injury by reducing pulmonary hypertension and minimizing neutrophil sequestration.

Original languageEnglish (US)
Pages (from-to)247-253
Number of pages7
JournalAnnals of Thoracic Surgery
Issue number1
StatePublished - Jul 2007

Bibliographical note

Funding Information:
Research for this study was funded by NIH RO1 HL 056093 (ILK) and NIH Training Grant 5 T32 HL007849 (ILK). The authors thank Sheila Hammond and Anthony Herring for their technical expertise and contributions and Kimberly Shockey for her statistical expertise.


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