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Selective Pulmonary Vasodilation by Intravenous Infusion of an Ultrashort Half‐life Nucleophile/Nitric Oxide Adduct

Background PROLI/NO (C5 H7 N3 O4 Na2 [center dot] CH3 OH) is an ultrashort‐acting nucleophile/NO adduct that generates NO (half‐life 2 s at 37 [degree sign] Celsius and pH 7.4). Because of its short half‐life, the authors hypothesized that intravenous 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 sub 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 micro gram [center dot] kg sup ‐1 [center dot] min sup ‐1 of SNP or 0.75, 1.5, 3, 6, and 12 micro gram [center dot] kg sup ‐1 [center dot] min sup ‐1 of PROLI/NO. 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 micro gram [center dot] kg sup ‐1 [center dot] min sup ‐1, which decreased pulmonary vascular resistance by 63% (P < 0.01) from pulmonary hypertensive baseline values without changing systemic vascular resistance. At 12 micro gram [center dot] kg sup ‐1 [center dot] min sup ‐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.