title: Preservation of cerebrovascular tone and reactivity by sodium channel inhibition in experimental prolonged asphyxia in piglets.
abstract: Sodium channels using cAMP as a second messenger play a role in the regulation of cerebral circulation and metabolism. Cerebrospinal fluid (CSF) cAMP levels have been shown to correlate with the degree and duration of hypoxic injury and outcome and to be an indicator of cerebral vascular reactivity. We hypothesize that sodium channel inhibition either before or at termination of experimental asphyxia will attenuate cerebrovascular alterations and maintain CSF cAMP levels. Three groups of piglets with closed cranial windows were studied: asphyxia or group 1 (n = 5) and two treatment groups. Pigs were treated with 50 mg/kg of sodium channel blocker before asphyxia (group 2, n = 6) and after the termination of asphyxia and start of reventilation (group 3, n = 6). Asphyxia was sustained over 60 min by ventilating piglets with 10% O2 gas mixture and decreasing minute ventilation followed by 60 min of reventilation with room air. Every 10 min, pial arterial diameters were measured, and CSF samples were collected for cAMP determination. Vascular reactivity to topically applied isoproterenol (10(-4) M) was evaluated 60 min after recovery. During asphyxia, cAMP levels in group 2 peaked and declined at a later time with mean values remaining significantly higher than those of groups 1 and 3. During reventilation, CSF cAMP concentrations were highest in group 3 and lowest in group 1. Pial arteriolar dilation occurred during asphyxia in all three groups but to a lesser degree in the pretreated group compared with groups 1 and 3. Pial arteriolar reactivity to isoproterenol postasphyxia was preserved in both groups 2 and 3. In summary, in newborn pigs, pretreatment with sodium channel blocker resulted in higher CSF cAMP levels and a lesser degree of pial arteriolar dilation during prolonged asphyxia. Pretreatment or treatment at reventilation restored vascular tone and reactivity.
authors.affiliation: Department of Pediatrics, The University of Tennessee, Memphis 38163, USA.
authors.forename: V
authors.initials: V
authors.lastname: Levine
authors.forename: M
authors.initials: M
authors.lastname: Pourcyrous
authors.forename: H S
authors.initials: HS
authors.lastname: Bada
authors.forename: H
authors.initials: H
authors.lastname: Parfenova
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: S B
authors.initials: SB
authors.lastname: Korones
authors.forename: C W
authors.initials: CW
authors.lastname: Leffler
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000503:physiopathology*; D001808:Blood Vessels / Q000503:physiopathology*; D001921:Brain / Q000098:blood supply*; D000242:Cyclic AMP / Q000134:cerebrospinal fluid; D005260:Female; D008297:Male; D009129:Muscle Tonus; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D026941:Sodium Channel Blockers; D013552:Swine
chemical_list: D026941:Sodium Channel Blockers; D000242:Cyclic AMP