Preservation of cerebrovascular tone and reactivity by sodium channel inhibition in experimental prolonged asphyxia in piglets

Vladimir Levine, Massroor Pourcyrous, Henrietta S. Bada, Elena Parfenova, Wenjian Yang, Sheldon B. Korones, Charles Leffler

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)376-380
Number of pages5
JournalPediatric Research
Volume47
Issue number3
DOIs
StatePublished - Jan 1 2000

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Sodium Channels
Asphyxia
Cerebrospinal Fluid
Sodium Channel Blockers
Blood Vessels
Isoproterenol
Dilatation
Cerebrovascular Circulation
Swine
Second Messenger Systems
Ventilation
Gases
Air
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health

Cite this

Preservation of cerebrovascular tone and reactivity by sodium channel inhibition in experimental prolonged asphyxia in piglets. / Levine, Vladimir; Pourcyrous, Massroor; Bada, Henrietta S.; Parfenova, Elena; Yang, Wenjian; Korones, Sheldon B.; Leffler, Charles.

In: Pediatric Research, Vol. 47, No. 3, 01.01.2000, p. 376-380.

Research output: Contribution to journalArticle

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