Selective pulmonary vasodilation by intravenous infusion of an ultrashort half-life nucleophile nitric oxide adduct

被引:14
作者
Adrie, C
Hirani, WM
Holzmann, A
Keefer, L
Zapol, WM
Hurford, WE [1 ]
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA
[2] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA
关键词
nitric oxide prodrugs; pulmonary hypertension; sheep; sodium nitroprusside;
D O I
10.1097/00000542-199801000-00027
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Background: PROLI/NO (C5H7/N3O4Na2 . CH3OH) is an ultrashort-acting nucleophile/NO adduct that generates NO (half-life 2 s at 37 degrees C and pH 7.4). Because of its short half-life, the authors hypothesized that intravenons administration of this compound would selectively dilate the pulmonary vasculature but cause little or no systemic hypotension, Methods; in eight awake healthy sheep with pulmonary Hypertension induced by 9,11-dideoxy-9 alpha,11 alpha-methanoepoxy prostaglandin F-2 alpha, the authors compared PROLI/NO with two reference drugs-inhaled NO, a well-studied selective pulmonary vasodilator, and intravenous sodium nitroprusside (SNP), a nonselective vasodilator. Sheep inhaled 10, 20, 40, and 80 parts per million NO or received intravenous infusions of 0.25, 0.5, 1, 2, and 4 mu g.kg(-1).min(-1) of SNP or 0.75, 1.5, 3, 6, and 12 mu g.kg(-1).min(-1) of PROLI/NB. The order of administration of the vasoactive drugs (NO, SNP, PROLI/NO) and their doses were randomized. Results: Inhaled NO selectively dilated the pulmonary vasculature. Intravenous SNP induced nonselective vasodilation of the systemic and pulmonary circulation. Intravenous PROLI/NO selectively vasodilated the pulmonary circulation at doses up to 6 mu g.kg(-1).min(-1), which decreased pulmonary vascular resistance by 63% (P < 0.01) from pulmonary hypertensive baseline values without changing systemic vascular resistance. At 12 mu g.kg(-1).min(-1), PROLI/NO decreased systemic and pulmonary vascular resistance and pressure. Exhaled NO concentrations were higher during PROLI/NO infusion than during SNP infusion (P < 0.01 with all data pooled), Conclusions: The results suggest that PROLI/NO could be a useful intravenous drug to vasodilate the pulmonary circulation selectively.
引用
收藏
页码:190 / 195
页数:6
相关论文
共 15 条
[1]   A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension [J].
Barst, RJ ;
Rubin, LJ ;
Long, WA ;
McGoon, MD ;
Rich, S ;
Badesch, DB ;
Groves, BM ;
Tapson, VF ;
Bourge, RC ;
Brundage, BH ;
Koerner, SK ;
Langleben, D ;
Keller, CA ;
Murali, S ;
Uretsky, BF ;
Clayton, LM ;
Jobsis, MM ;
Blackburn, SD ;
Shortino, D ;
Crow, JW .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 334 (05) :296-301
[2]  
FISHMAN AP, 1988, CECIL TXB MED, P293
[3]   HOMOGENEOUS CHEMILUMINESCENT MEASUREMENT OF NITRIC OXIDE WITH OZONE - IMPLICATIONS FOR CONTINUOUS SELECTIVE MONITORING OF GASEOUS AIR POLLUTANTS [J].
FONTIJN, A ;
SABADELL, AJ ;
RONCO, RJ .
ANALYTICAL CHEMISTRY, 1970, 42 (06) :575-&
[4]   INHALED NITRIC-OXIDE - A SELECTIVE PULMONARY VASODILATOR REVERSING HYPOXIC PULMONARY VASOCONSTRICTION [J].
FROSTELL, C ;
FRATACCI, MD ;
WAIN, JC ;
JONES, R ;
ZAPOL, WM .
CIRCULATION, 1991, 83 (06) :2038-2047
[6]   PULMONARY VASODILATOR RESPONSES TO NITROPRUSSIDE AND NITROGLYCERIN IN THE DOG [J].
KADOWITZ, PJ ;
NANDIWADA, P ;
GRUETTER, CA ;
IGNARRO, LJ ;
HYMAN, AI .
JOURNAL OF CLINICAL INVESTIGATION, 1981, 67 (03) :893-902
[7]  
Keefer LK, 1996, METHOD ENZYMOL, V268, P281
[8]  
PEARL RG, 1993, ANESTHESIOLOGY, V78, P413
[9]   INHALED NITRIC-OXIDE AS A CAUSE OF SELECTIVE PULMONARY VASODILATATION IN PULMONARY-HYPERTENSION [J].
PEPKEZABA, J ;
HIGENBOTTAM, TW ;
DINHXUAN, AT ;
STONE, D ;
WALLWORK, J .
LANCET, 1991, 338 (8776) :1173-1174
[10]   SELECTIVE PULMONARY VASODILATION BY INHALED NITRIC-OXIDE IS DUE TO HEMOGLOBIN INACTIVATION [J].
RIMAR, S ;
GILLIS, CN .
CIRCULATION, 1993, 88 (06) :2884-2887