Evaluation of inhaled .NO in a model of rat neonate brain injury caused by hypoxia-ischaemia.
OBJECTIVE
Inhaled NO (INO), at 5-40 parts per million (ppm) in the air, is indicated for treating neonatal hypoxic respiratory failure. Whether these doses of INO are protective or toxic towards brain was here evaluated in laboratory animals.


METHODS
In rat neonates (postnatal day 7), a brain injury based on permanent right carotid artery occlusion plus transient (90 min) respiratory hypoxia (8% O(2)) was challenged by two NO dosages (10 and 40 ppm) given either before, during or after transient hypoxia. Three weeks later, animal brains were studied for the loss of cerebral matter (infarct or atrophy).


RESULTS
In right hemispheres, significant increases (26-39%) in lesion sizes were induced by 40 and not 10 ppm INO, whatever the inhalation period. The two doses reduced significantly the left hemisphere volume only when NO was inhaled at the re-oxygenation period.


CONCLUSIONS
Our results suggest that high doses of INO, brain damaging events and inhalation at re-oxygenation might affect brain integrity when these conditions are cumulated. However, the clinical relevance of this (infarct or atrophy) and previously described (haematomas) brain toxicity associated with INO remains to be clarified in the human neonates, for instance through non-invasive cerebral imagery follow-up of patients given INO.
Joriot-Chekaf
Sylvie
S
Inserm Univ 045131 & EA 1046, IMPRT-IFR114, Pharmacology, Faculty of Medicine, University of Lille North of France, 59045 Lille, France.
Sfeir
Rony
R
Riou
Yvon
Y
Gressens
Pierre
P
Vallée
Louis
L
Bordet
Régis
R
Vamecq
Joseph
J
D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D001284:Atrophy / Q000139:chemically induced; D001921:Brain / Q000473:pathology; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology*; D002339:Carotid Arteries / Q000601:surgery; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D011247:Pregnancy; D051381:Rats; D012131:Respiratory Insufficiency / Q000188:drug therapy*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D014665:Vasodilator Agents; D009569:Nitric Oxide