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

Research output: Contribution to journalArticle

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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 1997
Externally publishedYes

Fingerprint

Pulmonary Hypertension
Vascular Resistance
Nitric Oxide
Lung
Drug Instillation
Arterial Pressure
Hemodynamics
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Nitric Oxide Donors
Thromboxanes
Nitroprusside
Trachea
Amines
Swine
(2-(dimethylamino)ethyl)phosphonic acid
Therapeutics

Keywords

  • Nitric oxide donor
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

Cite this

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

Intratracheal instillation of a novel NO/nucleophile adduct selectively reduces pulmonary hypertension. / Brilli, Richard J.; Krafte-Jacobs, Brian; Smith, Daniel J.; Roselle, Dominick; Passerini, Daniel; Vromen, Amos; Moore, Lori; Szabo, Csaba; Salzman, Andrew L.

In: Journal of Applied Physiology, Vol. 83, No. 6, 12.1997, p. 1968-1975.

Research output: Contribution to journalArticle

Brilli, RJ, Krafte-Jacobs, B, Smith, DJ, Roselle, D, Passerini, D, Vromen, A, Moore, L, Szabo, C & Salzman, AL 1997, 'Intratracheal instillation of a novel NO/nucleophile adduct selectively reduces pulmonary hypertension', Journal of Applied Physiology, vol. 83, no. 6, pp. 1968-1975.
Brilli RJ, Krafte-Jacobs B, Smith DJ, Roselle D, Passerini D, Vromen A et al. Intratracheal instillation of a novel NO/nucleophile adduct selectively reduces pulmonary hypertension. Journal of Applied Physiology. 1997 Dec;83(6):1968-1975.
Brilli, Richard J. ; Krafte-Jacobs, Brian ; Smith, Daniel J. ; Roselle, Dominick ; Passerini, Daniel ; Vromen, Amos ; Moore, Lori ; Szabo, Csaba ; Salzman, Andrew L. / Intratracheal instillation of a novel NO/nucleophile adduct selectively reduces pulmonary hypertension. In: Journal of Applied Physiology. 1997 ; Vol. 83, No. 6. pp. 1968-1975.
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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.",
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AB - 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.

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