To test the effectiveness of intravenous Zaprinast (M&B 22948; 2-o -propoxyphenyl-8-azapurin-6-one; Rhône-Poulenc Rorer, Dagenham, Essex, United Kingdom) in lung-injury models, Adrie et al. studied two groups of sheep in which saline lavage was used to induce lung injury. After collection of baseline hemodynamic measurements, the authors performed bilateral lung lavage with use of 0.5% (vol/vol) polyoxythylene–sorbitan monooleate in 37°C saline in 15 healthy sheep. In the first group of 10 sheep, 1, 5, 10, and 20 ppm inhaled nitric oxide (NO) was administered in random order before and after an intravenous Zaprinast infusion (2 mg/kg bolus, followed by 0.1 mg · kg−1min−1). In the second group of five sheep, inhaled NO was administered, in the same concentrations, before and after an intravenous infusion of Zaprinast solvent (0.05 m NaOH).
The authors found that intravenous administration of Zaprinast alone decreased pulmonary artery pressure but worsened gas exchange. Furthermore, the Zaprinast infusion abolished the ability of inhaled NO to improve pulmonary gas exchange and to reduce pulmonary artery pressure.
