S-nitroso-N-acetylpenicillamine (SNAP) during hemorrhagic shock improves mortality as a result of recovery from vascular hyporeactivity

Nitric oxide donors are protective against hemorrhagic shock (HS). However, no detailed investigation has been performed. We investigated this mechani sm using S-nitroso-N-acetylpenicillamine (SNAP). HS (mean arterial pressure : 40 mm Hg) was induced in 20 dogs. Sixty min after HS, the animals were tr eated with saline (Cont-Gr: n = 7) or SNAP;5 mu g . kg(-1) . 10 min(-1) fol lowed by 5 mu g . kg(-1) . h(-1) (SNAP-Gr: n = 7). After another 60 min, th e shed blood was reinfused. Reactivities to noradrenalin (NA), changes in h emodynamics, the plasma catecholamines, and nitric oxide derivatives were d etermined. In Cont-Gr, 3 dogs died at 90, 98, and 102 min after HS. In Cont -Gr, % changes of systolic arterial blood pressure to 1 and 2.5 mu g/kg of NA after the recovery from HS decreased from 23.7% +/- 4.1% (before HS) to 6.5% +/- 0.6% and from 50.1% +/- 7.7% (before HS) to 14.5% +/- 2.6%, respec tively (P < 0.01). In SNAP-Gr, reactivity to NA was maintained. At 120 min after HS, mean arterial pressure and cardiac output in SNAP-Gr increased bu t not in Cont-Gr. Plasma catecholamine levels in SNAP-Gr were suppressed co mpared with those of Cant-Gr. In conclusion, a small dose of SNAP during HS decreased the mortality of the dogs. This might have been caused in part b y residual vascular hyporeactivity. Implications: The administration of a s mall dose of S-nitroso-N-acetylpenicillamine (a nitric oxide donor), a dose which did not exert a significant vasodilator effect, was administered dur ing hemorrhagic shock in dogs. S-nitroso-N-acetylpenicillamine improved and decreased the mortality rate.