Inhaled Nitric Oxide Therapy Fails to Improve Outcome in Experimental Severe Influenza

Darwish, Ilyse; Miller, Chris; Kain, Kevin C.; Liles, W. Conrad

The objective of this study was to determine whether iNO administration could reduce viral load and improve survival in a murine model of severe influenza. Inhaled NO delivery would provide a safer and easier delivery method rather than administration of NO donors, as iNO is approved for treating term and near-term neonates with hypoxemic respiratory failure up to a dose of 80 parts per million (ppm) (26, 27) . It has been reported that exogenous gaseous NO (gNO) at a high dose of no less than 160 ppm and with five hours of continuous exposure, can elicit a non-specific antimicrobial response against a broad range of microorganisms in vitro (28) . In vivo, 160 ppm iNO treatment would result in NO binding to hemoglobin to form methemoglobin, resulting in reduced oxygen transport and hypoxemia, as well as the potential for elevated levels of the harmful NO metabo-lite NO2. However, Miller et al. (29) has shown that gNO in an intermittent delivery regimen of 160 ppm for 30 min every 3.5 hours can prevent methemoglobinemia and reduce the potential of host cell toxicity in vitro and in vivo (Miller C, personal communication), while retaining antimicrobial properties in vitro.