title: Asphyxia and therapeutic hypothermia modulate plasma nitrite concentrations and carotid vascular resistance in preterm fetal sheep.
abstract: In this study, we tested the hypothesis that cerebral hypoperfusion after asphyxia and induced hypothermia is associated with reduced circulating nitrite levels as an index of nitric oxide synthase (NOS) activity. The preterm fetal sheep at 0.7 gestation (103-104 days, term = 147 days) received 25-minute umbilical cord occlusion, followed by mild whole-body cooling from 30 minutes to 72 hours after occlusion. Occlusion and induced hypothermia were independently associated with reduced carotid vascular conductance (CaVC) from 2 to 72 hours, and with transiently suppressed plasma nitrite levels at 6 hours. There was a significant within-subjects correlation (r(2) = 0.33, P = .002) between CaVC and plasma nitrite values in the first 24 hours after occlusion but not after sham occlusion. These findings suggest that in preterm fetal sheep, changes in NOS activity are an important mediator of changes in carotid vascular tone in the early recovery phase after asphyxia and may help mediate some of the vascular effects of induced hypothermia.
authors.affiliation: Department of Physiology, University of Auckland, Auckland, New Zealand.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Barrett
authors.affiliation: Department of Physiology, University of Auckland, Auckland, New Zealand.
authors.forename: Laura
authors.initials: L
authors.lastname: Bennet
authors.affiliation: Department of Pediatrics and Center for Perinatal Biology, Division of Neonatology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Arlin B
authors.initials: AB
authors.lastname: Blood
authors.affiliation: Department of Physiology, University of Auckland, Auckland, New Zealand.
authors.forename: Guido
authors.initials: G
authors.lastname: Wassink
authors.affiliation: Department of Physiology, University of Auckland, Auckland, New Zealand aj.gunn@auckland.ac.nz.
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Gunn
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D002339:Carotid Arteries / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D002561:Cerebrovascular Disorders / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D005865:Gestational Age; D007036:Hypothermia, Induced / Q000009:adverse effects*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000097:blood*; D047928:Premature Birth; D012756:Sheep; D013997:Time Factors; D014655:Vascular Resistance
chemical_list: D009573:Nitrites; D019001:Nitric Oxide Synthase
keywords: blood flow; fetal sheep; nitric oxide; therapeutic hypothermia
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