Retrograde perfusion with a sodium channel antagonist provides ischemic spinal cord protection

James J. Gangemi, John A. Kern, Scott D. Ross, Kimberly S. Shockey, Irving L. Kron, Curtis G. Tribble

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background. Neuronal voltage-dependent sodium channel antagonists have been shown to provide neuroprotection in focal and global cerebral ischemic models. We hypothesized that retrograde spinal cord venous perfusion with phenytoin, a neuronal voltage-dependent sodium channel antagonist, would provide protection during prolonged spinal cord ischemia. Methods. In a rabbit model, spinal cord ischemia was induced for 45 minutes. Six groups of animals were studied. Controls (group I, n = 8) received no intervention during aortic cross-clamping. Group II (n = 8) received systemic phenytoin (100 mg). Group III (n = 4) received systemic phenytoin (200 mg). Group IV (n = 8) received retrograde infusion of room temperature saline (22°C) only. Group V (n = 8) and group VI (n = 9) received retrograde infusion of 50 mg and 100 mg of phenytoin, respectively, (infusion rate: 0.8 mL · kg-1 · min-1 during the ischemic period). Mean arterial blood pressure was monitored continuously. Animals were allowed to recover for 24 hours before assessment of neurologic function using the Tarlov scale. Results. Tarlov scores (0 = complete paraplegia, 1 = slight lower limb movement, 2 = sits with assistance, 3 = sits alone, 4 = weak hop, 5 = normal hop) were as follows (mean ± SEM): group I, 0.50 ± 0.50; group II, 0.25 ± 0.46; group IV, 1.63 ± 0.56; group V, 4.13 ± 0.23; and group VI, 4.22 ± 0.22 (p < 0.0001 V, VI versus I, II, IV by analysis of variance). No differences in mean arterial blood pressure were observed. All animals in group III became profoundly hypotensive and died before the conclusion of the 45-minute ischemic time. Conclusions. Retrograde venous perfusion of the spinal cord with phenytoin, a voltage-sensitive sodium channel blocker, is safe and provides significant protection during prolonged spinal cord ischemia. (C) 2000 by The Society of Thoracic Surgeons.

Original languageEnglish (US)
Pages (from-to)1744-1748
Number of pages5
JournalAnnals of Thoracic Surgery
Volume69
Issue number6
DOIs
StatePublished - Jun 2000
Externally publishedYes

Fingerprint

Sodium Channels
Phenytoin
Spinal Cord Ischemia
Spinal Cord
Perfusion
Arterial Pressure
Humulus
Sodium Channel Blockers
Paraplegia
Constriction
Nervous System
Lower Extremity
Analysis of Variance
Rabbits
Control Groups
Temperature

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Retrograde perfusion with a sodium channel antagonist provides ischemic spinal cord protection. / Gangemi, James J.; Kern, John A.; Ross, Scott D.; Shockey, Kimberly S.; Kron, Irving L.; Tribble, Curtis G.

In: Annals of Thoracic Surgery, Vol. 69, No. 6, 06.2000, p. 1744-1748.

Research output: Contribution to journalArticle

Gangemi, James J. ; Kern, John A. ; Ross, Scott D. ; Shockey, Kimberly S. ; Kron, Irving L. ; Tribble, Curtis G. / Retrograde perfusion with a sodium channel antagonist provides ischemic spinal cord protection. In: Annals of Thoracic Surgery. 2000 ; Vol. 69, No. 6. pp. 1744-1748.
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abstract = "Background. Neuronal voltage-dependent sodium channel antagonists have been shown to provide neuroprotection in focal and global cerebral ischemic models. We hypothesized that retrograde spinal cord venous perfusion with phenytoin, a neuronal voltage-dependent sodium channel antagonist, would provide protection during prolonged spinal cord ischemia. Methods. In a rabbit model, spinal cord ischemia was induced for 45 minutes. Six groups of animals were studied. Controls (group I, n = 8) received no intervention during aortic cross-clamping. Group II (n = 8) received systemic phenytoin (100 mg). Group III (n = 4) received systemic phenytoin (200 mg). Group IV (n = 8) received retrograde infusion of room temperature saline (22°C) only. Group V (n = 8) and group VI (n = 9) received retrograde infusion of 50 mg and 100 mg of phenytoin, respectively, (infusion rate: 0.8 mL · kg-1 · min-1 during the ischemic period). Mean arterial blood pressure was monitored continuously. Animals were allowed to recover for 24 hours before assessment of neurologic function using the Tarlov scale. Results. Tarlov scores (0 = complete paraplegia, 1 = slight lower limb movement, 2 = sits with assistance, 3 = sits alone, 4 = weak hop, 5 = normal hop) were as follows (mean ± SEM): group I, 0.50 ± 0.50; group II, 0.25 ± 0.46; group IV, 1.63 ± 0.56; group V, 4.13 ± 0.23; and group VI, 4.22 ± 0.22 (p < 0.0001 V, VI versus I, II, IV by analysis of variance). No differences in mean arterial blood pressure were observed. All animals in group III became profoundly hypotensive and died before the conclusion of the 45-minute ischemic time. Conclusions. Retrograde venous perfusion of the spinal cord with phenytoin, a voltage-sensitive sodium channel blocker, is safe and provides significant protection during prolonged spinal cord ischemia. (C) 2000 by The Society of Thoracic Surgeons.",
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T1 - Retrograde perfusion with a sodium channel antagonist provides ischemic spinal cord protection

AU - Gangemi, James J.

AU - Kern, John A.

AU - Ross, Scott D.

AU - Shockey, Kimberly S.

AU - Kron, Irving L.

AU - Tribble, Curtis G.

PY - 2000/6

Y1 - 2000/6

N2 - Background. Neuronal voltage-dependent sodium channel antagonists have been shown to provide neuroprotection in focal and global cerebral ischemic models. We hypothesized that retrograde spinal cord venous perfusion with phenytoin, a neuronal voltage-dependent sodium channel antagonist, would provide protection during prolonged spinal cord ischemia. Methods. In a rabbit model, spinal cord ischemia was induced for 45 minutes. Six groups of animals were studied. Controls (group I, n = 8) received no intervention during aortic cross-clamping. Group II (n = 8) received systemic phenytoin (100 mg). Group III (n = 4) received systemic phenytoin (200 mg). Group IV (n = 8) received retrograde infusion of room temperature saline (22°C) only. Group V (n = 8) and group VI (n = 9) received retrograde infusion of 50 mg and 100 mg of phenytoin, respectively, (infusion rate: 0.8 mL · kg-1 · min-1 during the ischemic period). Mean arterial blood pressure was monitored continuously. Animals were allowed to recover for 24 hours before assessment of neurologic function using the Tarlov scale. Results. Tarlov scores (0 = complete paraplegia, 1 = slight lower limb movement, 2 = sits with assistance, 3 = sits alone, 4 = weak hop, 5 = normal hop) were as follows (mean ± SEM): group I, 0.50 ± 0.50; group II, 0.25 ± 0.46; group IV, 1.63 ± 0.56; group V, 4.13 ± 0.23; and group VI, 4.22 ± 0.22 (p < 0.0001 V, VI versus I, II, IV by analysis of variance). No differences in mean arterial blood pressure were observed. All animals in group III became profoundly hypotensive and died before the conclusion of the 45-minute ischemic time. Conclusions. Retrograde venous perfusion of the spinal cord with phenytoin, a voltage-sensitive sodium channel blocker, is safe and provides significant protection during prolonged spinal cord ischemia. (C) 2000 by The Society of Thoracic Surgeons.

AB - Background. Neuronal voltage-dependent sodium channel antagonists have been shown to provide neuroprotection in focal and global cerebral ischemic models. We hypothesized that retrograde spinal cord venous perfusion with phenytoin, a neuronal voltage-dependent sodium channel antagonist, would provide protection during prolonged spinal cord ischemia. Methods. In a rabbit model, spinal cord ischemia was induced for 45 minutes. Six groups of animals were studied. Controls (group I, n = 8) received no intervention during aortic cross-clamping. Group II (n = 8) received systemic phenytoin (100 mg). Group III (n = 4) received systemic phenytoin (200 mg). Group IV (n = 8) received retrograde infusion of room temperature saline (22°C) only. Group V (n = 8) and group VI (n = 9) received retrograde infusion of 50 mg and 100 mg of phenytoin, respectively, (infusion rate: 0.8 mL · kg-1 · min-1 during the ischemic period). Mean arterial blood pressure was monitored continuously. Animals were allowed to recover for 24 hours before assessment of neurologic function using the Tarlov scale. Results. Tarlov scores (0 = complete paraplegia, 1 = slight lower limb movement, 2 = sits with assistance, 3 = sits alone, 4 = weak hop, 5 = normal hop) were as follows (mean ± SEM): group I, 0.50 ± 0.50; group II, 0.25 ± 0.46; group IV, 1.63 ± 0.56; group V, 4.13 ± 0.23; and group VI, 4.22 ± 0.22 (p < 0.0001 V, VI versus I, II, IV by analysis of variance). No differences in mean arterial blood pressure were observed. All animals in group III became profoundly hypotensive and died before the conclusion of the 45-minute ischemic time. Conclusions. Retrograde venous perfusion of the spinal cord with phenytoin, a voltage-sensitive sodium channel blocker, is safe and provides significant protection during prolonged spinal cord ischemia. (C) 2000 by The Society of Thoracic Surgeons.

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