PMID- 12411809
OWN - NLM
STAT- MEDLINE
DCOM- 20021127
LR  - 20201208
IS  - 0003-3022 (Print)
IS  - 0003-3022 (Linking)
VI  - 97
IP  - 5
DP  - 2002 Nov
TI  - Reactive oxygen species scavengers attenuate endotoxin-induced impairment of 
      hypoxic pulmonary vasoconstriction in mice.
PG  - 1227-33
AB  - BACKGROUND: Sepsis and endotoxemia attenuate hypoxic pulmonary vasoconstriction 
      (HPV), thereby impairing systemic oxygenation. Reactive oxygen species (ROS) are 
      implicated in the pathogenesis of sepsis-induced lung injury. The authors 
      investigated whether treatment with scavengers of ROS prevents impairment of HPV 
      in mice challenged with endotoxin. METHODS: The pulmonary vasoconstrictor 
      response to left mainstem bronchus occlusion (LMBO) was studied in anesthetized 
      mice 22 h after an intraperitoneal challenge with saline solution or 10 mg/kg 
      Escherichia coli endotoxin. In some mice, challenge with saline solution or 
      endotoxin was followed after 1 h with intraperitoneal or intratracheal 
      administration of the ROS scavengers N-acetylcysteine or EUK-8. Myeloperoxidase 
      activity and nitric oxide synthase-2 gene expression were measured in lung 
      tissues. RESULTS: The LMBO increased left pulmonary vascular resistance by 106 
      +/- 24% in saline-challenged control mice but by only 23 +/- 12% (P < 0.05) in 
      endotoxin-challenged mice. Intraperitoneal administration of N-acetylcysteine or 
      EUK-8 1 h after endotoxin challenge attenuated the endotoxin-induced impairment 
      of HPV (58 +/- 6% and 68 +/- 10%, respectively; both P< 0.05 endotoxin-challenged 
      mice). Intratracheal administration of ROS scavengers 1 h after endotoxin 
      challenge was equally effective but required lower doses than systemic treatment. 
      Administration of the ROS scavengers 22 h after endotoxin challenge did not 
      restore HPV. CONCLUSIONS: Administration of N-acetylcysteine or EUK-8 1 h after 
      endotoxin challenge in mice prevented the impairment of HPV after LMBO. Early 
      therapy with ROS scavengers, either systemically or by inhalation, may provide a 
      means to preserve HPV in sepsis-associated acute lung injury.
FAU - Baboolal, Hemanth A
AU  - Baboolal HA
AD  - Department of Anesthesia and Critical Care, Cardiovascular Research Center, 
      Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
FAU - Ichinose, Fumito
AU  - Ichinose F
FAU - Ullrich, Roman
AU  - Ullrich R
FAU - Kawai, Noriko
AU  - Kawai N
FAU - Bloch, Kenneth D
AU  - Bloch KD
FAU - Zapol, Warren M
AU  - Zapol WM
LA  - eng
GR  - HL-42397/HL/NHLBI NIH HHS/United States
GR  - HL-57172/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Anesthesiology
JT  - Anesthesiology
JID - 1300217
RN  - 0 (Antioxidants)
RN  - 0 (Endotoxins)
RN  - 0 (Ethylenediamines)
RN  - 0 (Organometallic Compounds)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 53177-12-1 (N,N'-bis(salicylideneamino)ethane-manganese(II))
RN  - 67924-63-4 (endotoxin, Escherichia coli)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/*pharmacology
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Cell Hypoxia/*physiology
MH  - Endotoxins/*toxicity
MH  - Ethylenediamines/*pharmacology
MH  - Female
MH  - Male
MH  - Mice
MH  - Nitric Oxide Synthase/genetics
MH  - Nitric Oxide Synthase Type II
MH  - Organometallic Compounds/*pharmacology
MH  - Peroxidase/metabolism
MH  - Pulmonary Circulation/*drug effects
MH  - RNA, Messenger/analysis
MH  - Reactive Oxygen Species/*metabolism
MH  - Respiratory Distress Syndrome/prevention & control
MH  - Vasoconstriction/*drug effects
EDAT- 2002/11/02 04:00
MHDA- 2002/11/28 04:00
CRDT- 2002/11/02 04:00
PHST- 2002/11/02 04:00 [pubmed]
PHST- 2002/11/28 04:00 [medline]
PHST- 2002/11/02 04:00 [entrez]
AID - 00000542-200211000-00028 [pii]
AID - 10.1097/00000542-200211000-00028 [doi]
PST - ppublish
SO  - Anesthesiology. 2002 Nov;97(5):1227-33. doi: 10.1097/00000542-200211000-00028.