Two aerosolized nitric oxide adducts as selective pulmonary vasodilators for acute pulmonary hypertension

Study objectives: To determine the selective vasodilatory effects of two inhaled “NONOate” aerosols in a closed chest pig model of acute pulmonary hypertension (APH). Methods: APH was induced by IV infusion of the prostaglandin H2/thromboxane A2 receptor agonist (U46619). Aerosolized diethylenetriamine nitric oxide (NO) adduct (DETA/NO, n 4), dipropylenetriamine NO adduct (DPTA/NO, n 4) [60 mol each], or placebo (n 4) was delivered via the trachea. Hemodynamic parameters and blood samples were measured before and after inhalation therapy. Results: Compared to control animals, pulmonary vascular resistance and pulmonary arterial pressure were significantly reduced from 10 to 105 min after DETA/NO administration and from 10 to 45 min after DPTA/NO aerosol administration (p < 0.05). Both aerosols had no significant effect on systemic vascular resistance or systemic BP. Serum nitrite significantly increased after the inhalation of both NONOates (p < 0.01). There was a tendency for reduced intrapulmonary shunting, particularly after treatment with DETA/NO. Conclusion: Both DETA/NO and DPTA/NO administered as aerosols selectively reduced pulmonary hypertension induced by U46619. (CHEST 2003; 123:869 – 874) Abbreviations: ANOVA analysis of variance; APH acute pulmonary hypertension; CI cardiac index; DETA/ NO diethylenetriamine nitric oxide adduct; DPTA/NO dipropylenetriamine nitric oxide adduct; MPAP mean pulmonary artery pressure; NO nitric oxide; NO2 - nitrite; PAP pulmonary artery pressure; PCWP pulmonary capillary wedge pressure; PVRI pulmonary vascular resistance index; SBP systemic BP; SPV selective pulmonary