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

被引:32
作者
Brilli, RJ
KrafteJacobs, B
Smith, DJ
Roselle, D
Passerini, D
Vromen, A
Moore, L
Szabo, C
Salzman, AL
机构
[1] UNIV AKRON,DEPT CHEM,AKRON,OH 44325
[2] CHILDRENS HOSP,MED CTR,DIV PEDIAT SURG,CINCINNATI,OH 45229
关键词
nitric oxide donor; pulmonary hypertension;
D O I
10.1152/jappl.1997.83.6.1968
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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.
引用
收藏
页码:1968 / 1975
页数:8
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