Intratracheal instillation of a novel NO/nucleophile adduct selectively reduces pulmonary hypertension

Richard J. Brilli, Brian Krafte-Jacobs, Daniel J. Smith, Dominick Roselle, Daniel Passerini, Amos Vromen, Lori Moore, Csaba Szabo, Andrew L. Salzman

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    35 Scopus citations

    Abstract

    We examined the pulmonary and systemic hemodynamic effects of administering soluble nitric oxide (NO) donor compounds (NO/nucleophile adducts, i.e., NONOates) directly into the trachea of animals with experimentally induced pulmonary hypertension. Steady-state pulmonary hypertension was created by using the thromboxane agonist U-46619. Yorkshire pigs were randomly assigned to one of four groups: group 1, intratracheal saline (control; n = 8); group 2, intratracheal sodium nitroprusside (n = 6); group 3, intratracheal ethylputreanine NONOate (n = 6); and group 4, intratracheal 2-(dimethylamino)-ethylputreanine NONOate (DMAEP/NO; n = 6). Pulmonary and systemic hemodynamics were monitored after drug instillation. Group 4 had significant reductions in pulmonary vascular resistance index (PVRI) at all time points compared with steady state and compared with group 1 (P < 0.05), whereas systemic vascular resistance index did not change. The mean change in mean pulmonary arterial pressure in group 4 was -33.1 ± 1.2% compared with +6.4 ± 1.3% in group 1 (P < 0.001), and the mean change in mean arterial pressure was -9.3 ± 0.7% compared with a control value of - 0.9 ± 0.5% (P < 0.05). Groups 2 and 3 had significant decreases in both PVRI and systemic vascular resistance index compared with steady state and with group 1. In conclusion, intratracheal instillation of a polar-charged tertiary amine NONOate DMAEP/NO results in the selective reduction of PVRI. Intermittent intratracheal instillation of selective NONOates may be an alternative to continuously inhaled NO in the treatment of pulmonary hypertension.

    Original languageEnglish (US)
    Pages (from-to)1968-1975
    Number of pages8
    JournalJournal of Applied Physiology
    Volume83
    Issue number6
    StatePublished - Dec 1 1997

    Keywords

    • Nitric oxide donor
    • Pulmonary hypertension

    ASJC Scopus subject areas

    • Physiology
    • Physiology (medical)

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    Brilli, R. J., Krafte-Jacobs, B., Smith, D. J., Roselle, D., Passerini, D., Vromen, A., Moore, L., Szabo, C., & Salzman, A. L. (1997). Intratracheal instillation of a novel NO/nucleophile adduct selectively reduces pulmonary hypertension. Journal of Applied Physiology, 83(6), 1968-1975.