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(Chest. 2005;128:2910-2917.)
© 2005 American College of Chest Physicians

Effects of Inhaled Nitric Oxide on Inflammation and Apoptosis After Cardiopulmonary Bypass*

Driss El Kebir, PhD; Bernard Hubert, MD; Rame Taha, MD; Eric Troncy, PhD; Tianlong Wang, MD; Dominique Gauvin, BS; Marius Gangal, MD, PhD and Gilbert Blaise, MD

* From the Laboratory of Anesthesia (Drs. El Kebir, Taha, Troncy, Wang, Gangal, and Blaise, and Ms. Gauvin), Department of Anesthesia and Research Center, Center Hospitalier de Ùniversitie de Montreal, Hopital Notre-Dame, Montreal, QC, Canada; and Department of Anesthesia and Intensive Care Medicine (Dr. Hubert), CHU Liege, Belgium.

Correspondence to: Gilbert Blaise, MD, Center Hospitalier de Ùniversitie de Montreal–Hopital Notre-Dame Hospital, Laboratory of Anesthesia, Deschamps Pavilion, Room FS-1136, 1560 Sherbrooke St East, Montreal, QC, Canada, H2L 4M1; e-mail: blaisegil{at}sympatico.ca

Background: Cardiopulmonary bypass (CPB), a procedure often used during cardiac surgery, is associated with an inflammatory process that leads to lung injury. We hypothesized that inhaled nitric oxide (INO), which has anti-inflammatory properties, possesses the ability to modulate lung cell apoptosis and prevent CPB-induced inflammation.

Methods: Twenty male pigs were randomly classified into four groups: sham, sham plus INO, CPB, and CPB plus INO. INO (20 ppm) was administered for 24 h after anesthesia. CPB was performed 90 min into INO treatment. BAL fluid and blood were collected at time 0 (before CPB), at 4 h after beginning CPB, and 24 h after beginning CPB (T24).

Results: At T24, BAL interleukin (IL)-8 levels and neutrophil percentages were elevated significantly in the CPB group. At T24, INO reduced IL-8 concentrations and attenuated the increase of neutrophil percentage in the CPB-plus-INO group. Nitrite-plus-nitrate (NOx) concentrations were decreased significantly in groups without INO. Moreover, animals treated with INO showed higher rates of pulmonary apoptosis compared to their respective control groups except for the sham-plus-INO group, in which they were diminished.

Conclusion: These results demonstrate that NOx production is reduced after CPB, and that INO acts as an anti-inflammatory agent by decreasing neutrophil numbers and their major chemoattractant, IL-8. INO also increases cell apoptosis in the lungs during inflammatory conditions, which may explain, in part, how it resolves pulmonary inflammation.

Key Words: cardiopulmonary bypass • endothelial nitric oxide synthase • inhaled nitric oxide






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