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 mechanism 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 treated with saline (Cont-Gr: n = 7) or SNAP; 5 microg. kg(-1). 10 min(-1) followed by 5 microg. kg(-1). h(-1) (SNAP-Gr: n = 7). After another 60 min, the shed blood was reinfused. Reactivities to noradrenalin (NA), changes in hemodynamics, the plasma catecholamines, and nitric oxide derivatives were determined. 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 microg/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%, respectively (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 but not in Cont-Gr. Plasma catecholamine levels in SNAP-Gr were suppressed compared with those of Cont-Gr. In conclusion, a small dose of SNAP during HS decreased the mortality of the dogs. This might have been caused in part by residual vascular hyporeactivity.


CONCLUSIONS
The administration of a small dose of S-nitroso-N-acetylpenicillamine (a nitric oxide donor), a dose which did not exert a significant vasodilator effect, was administered during hemorrhagic shock in dogs. S-nitroso-N-acetylpenicillamine improved the vascular hyporeactivity to noradrenaline and decreased the mortality rate.
Sato
S
S
Department of Anesthesiology and Intensive Care, Hamamatsu University School of Medicine, Hamamatsu, Japan. ssato@hama-med.ac.jp
Suzuki
A
A
Nakajima
Y
Y
Iwamoto
T
T
Bito
H
H
Miyabe
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000503:physiopathology*; D002395:Catecholamines / Q000097:blood; D004285:Dogs; D004562:Electrocardiography; D006439:Hemodynamics / Q000187:drug effects; D009569:Nitric Oxide / Q000097:blood; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D009638:Norepinephrine / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D026423:S-Nitroso-N-Acetylpenicillamine; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D015996:Survival Rate; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002395:Catecholamines; D020030:Nitric Oxide Donors; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine; D009638:Norepinephrine