Dosage of inhaled nitric oxide: a simple method for experimental studies

Few studies on treatment with inhaled nitric oxide (NOi) have been carried out in small laboratory animals yet, since commercially available dosing devices are not appropriate in this setting for technical or financial reasons. The aim of our study was to establish and validate a simple, cost-effective system for the application of NOi in small animals. The system mixes NOi with constant-flow inspiratory gas. A gas blender allows for a mixture of nitrogen, oxygen, and NO dissolved in nitrogen. A formula using the desired inspiratory oxygen fraction and the desired concentration of NOi as independent variables derives a somewhat higher inspiratory oxygen fraction, which is preset using an oximeter. Then the flow of NO in nitrogen is started, lowering the inspiratory oxygen fraction to the initially desired value, thereby adding NOi in the desired concentration. The method was validated by 153 adjustments, covering a variety of oxygen fractions and concentrations of NOi. NOi was measured by chemiluminescence as reference method. A close correlation (R = 0.994) was found, and the regression line was close to the line of identity with y = -0.0994 + 1.048x. No systematic errors could be identified. We conclude that the method described may serve as a simple, cost-effective way to administer NOi to small animals.