Asphyxia and Therapeutic Hypothermia Modulate Plasma Nitrite Concentrations and Carotid Vascular Resistance in Preterm Fetal Sheep

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.