New method for absolute spinal cord ischemia protection in rabbits

J Vasc Surg. 2011 Oct;54(4):1109-16. doi: 10.1016/j.jvs.2011.04.043. Epub 2011 Sep 3.

Abstract

Objective: This study aims to establish a superior procedure to prevent spinal cord damage after severe spinal cord ischemia during aortic surgery. We examined the synergistic effect of topical hypothermia of the spinal cord combined with radical scavenger infusion into the clamped segment of the aorta to prevent spinal cord damage in an animal model.

Methods: Spinal cord ischemia was induced in rabbits by clamping the aorta between the renal artery and aortic bifurcation for 30 minutes. Rabbits were divided into four groups of 16 each: group I, sham-operated; group II, edaravone (6 mL, 4°C, 1 mg/kg); group III, saline (6 mL, 4°C) with transvertebral cooling pads; group IV, edaravone (6 mL, 4°C, 1 mg/kg) and transvertebral cooling pads. Solutions were injected into the clamped segment of the aorta. Postoperative assessments included the Tarlov score, spinal cord histopathology, and measurement of malondialdehyde levels in the spinal cord tissue.

Results: At 48 hours after reperfusion, the mean Tarlov scores in groups I, II, III, and IV were 4.0, 1.5, 1.9, and 4.0, respectively. The mean number of normal motor neurons was significantly higher in groups I (54.1) and IV (53.7) than in groups II (32.8) and III (36.3; P < .001). The mean malondialdehyde level in groups I (19.8 nmol/mL) and IV (22.6 nmol/mL) was significantly lower than in groups II (64.8 nmol/mL) and III (60.9 nmol/mL; P < .001). At 168 hours after reperfusion, the mean Tarlov scores in groups I, II, III, and IV were 4.0, 1.1, 1.3, and 4.0, respectively. The mean number of normal motor neurons was significantly higher in groups I (52.9) and IV (50.8) than in groups II (22.4) and III (25.9; P < .001). The mean malondialdehyde level in groups I (20.7 nmol/mL) and IV (23.4 nmol/mL) was significantly lower than in groups II (68.9 nmol/mL) and III (61.6 nmol/mL; P < .001).

Conclusion: In a rabbit model with aortic clamping up to 30 minutes, which consistently produces complete paraplegia in rabbits, spinal cord damage was partially reduced by topical cooling with transvertebral cooling pads or the injection of edaravone into the clamped segment of aorta, but was more effectively protected by a combined use of these two strategies.

MeSH terms

  • Animals
  • Antipyrine / administration & dosage
  • Antipyrine / analogs & derivatives*
  • Aorta / surgery*
  • Biomarkers / metabolism
  • Combined Modality Therapy
  • Constriction
  • Disease Models, Animal
  • Edaravone
  • Free Radical Scavengers / administration & dosage*
  • Hypothermia, Induced*
  • Infusions, Intra-Arterial
  • Malondialdehyde / metabolism
  • Motor Neurons / drug effects
  • Motor Neurons / pathology
  • Neurologic Examination
  • Neuroprotective Agents / administration & dosage*
  • Oxidative Stress / drug effects
  • Paraplegia / prevention & control
  • Rabbits
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Severity of Illness Index
  • Spinal Cord Ischemia / metabolism
  • Spinal Cord Ischemia / pathology
  • Spinal Cord Ischemia / physiopathology
  • Spinal Cord Ischemia / prevention & control*
  • Time Factors
  • Vascular Surgical Procedures / adverse effects*

Substances

  • Biomarkers
  • Free Radical Scavengers
  • Neuroprotective Agents
  • Malondialdehyde
  • Edaravone
  • Antipyrine