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Vol. 83, Issue 6, 1968-1975, December 1997
1 Division of Critical Care
Medicine,
Received 10 March 1997; accepted in final form 31 July 1997.
Brilli, Richard J., Brian Krafte-Jacobs, Daniel J. Smith,
Dominick Roselle, Daniel Passerini, Amos Vromen, Lori Moore, Csaba
Szabó, and Andrew L. Salzman. Intratracheal instillation of
a novel NO/nucleophile adduct selectively reduces pulmonary hypertension. J. Appl. Physiol. 83(6):
1968-1975, 1997.
nitric oxide donor; pulmonary hypertension
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.
0161-7567/97 $5.00
Copyright © 1997 the American Physiological Society
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