Effects of intravenous Zaprinast and inhaled nitric oxide on pulmonary hemodynamics and gas exchange in an ovine model of acute respiratory distress syndrome

Background: Inhaled nitric oxide (NO) selectively dilates the pulmonary vas culature and improves gas exchange in acute respiratory distress syndrome. Because of the very short half-life of NO, inhaled NO is administered conti nuously. Intravenous Zaprinast (2-o-propoxyphenyl-8-azapurin-6-one), a cycl ic guanosine monophosphate phosphodiesterase inhibitor, increases the effic acy and prolongs the duration of action of inhaled NO in models of acute pu lmonary hypertension. Its efficacy in lung injury models is uncertain, The authors hypothesized that the use of intravenous Zaprinast would have simil ar beneficial effects when used in combination with inhaled NO to improve o xygenation and dilate the pulmonary vasculature in a diffuse model of acute lung injury. Methods: The authors studied two groups of sheep with lung injury produced by saline lavage. In the first group, 0, 5, 10, and 20 ppm of inhaled NO we re administered in a random order before and after an intravenous Zaprinast infusion (2 mg/kg bolus followed by 0.1 mg . kg(-1) . min(-1)). In the sec ond group, inhaled NO was administered at the same concentrations before an d after an intravenous infusion of Zaprinast solvent (0.05 M NaOH), Results: After lavage, inhaled NO decreased pulmonary arterial pressure and resistance with no systemic hemodynamic effects, increased arterial oxygen partial pressure, and decreased venous admixture (all P < 0.05). The intra venous administration of Zaprinast alone decreased pulmonary artery pressur e but worsened gas exchange (P < 0.05). Zaprinast infusion abolished the be neficial ability of inhaled NO to improve pulmonary gas exchange and reduce pulmonary artery pressure (P < 0.05 vs. control), Conclusions: This study suggests that nonselective vasodilation induced by intravenously administered Zaprinast at the dose used in our study not only worsens gas exchange, but also abolishes the beneficial effects of inhaled NO.