Leukocyte filtration improves brain protection after a prolonged period of hypothermic circulatory arrest: A study in a chronic porcine model

J Thorac Cardiovasc Surg. 2000 Dec;120(6):1131-41. doi: 10.1067/mtc.2000.111050.

Abstract

Background: Ischemic cerebral injury follows a well-attested sequence of events, including 3 phases: depolarization, biochemical cascade, and reperfusion injury. Leukocyte infiltration and cytokine-mediated inflammatory reaction are known to play a pivotal role in the reperfusion phase. These events exacerbate the brain injury by impairing the normal microvascular perfusion and through the release of cytotoxic enzymes. The aim of the present study was to determine whether a leukocyte-depleting filter (LeukoGuard LG6, Pall Biomedical, Portsmouth, United Kingdom) could improve the cerebral outcome after hypothermic circulatory arrest.

Methods: Twenty pigs (23-30 kg) were randomly assigned to undergo cardiopulmonary bypass with or without a leukocyte-depleting filter before and after a 75-minute period of hypothermic circulatory arrest at 20 degrees C. Electroencephalographic recovery, S-100beta protein levels, and cytokine levels (interleukin 1beta, interleukin 8, and tumor necrosis factor alpha) were recorded up to the first postoperative day. Postoperatively, all animals were evaluated daily until death or until electively being put to death on day 7 by using a quantitative behavioral score. A postmortem histologic analysis of the brain was carried out on all animals.

Results: The rate of mortality was 2 of 10 in the leukocyte-depletion group and 5 of 10 in control animals. The risk for early death in control animals was 2.5 (95% confidence interval, 0.63-10.0) times higher than that of the leukocyte-depleted animals. The median behavioral score at day 7 was higher in the leukocyte-depletion group (8.5 vs 3.5; P =.04). The median of total histopathologic score was 8.5 in the leukocyte-depletion group and 15.5 in the control group (P =.005).

Conclusion: A leukocyte-depleting filter improves brain protection after a prolonged period of hypothermic circulatory arrest.

MeSH terms

  • Animals
  • Brain Injuries / blood
  • Brain Injuries / etiology*
  • Brain Injuries / mortality
  • Brain Injuries / pathology
  • Brain Injuries / prevention & control*
  • Calcium-Binding Proteins / blood
  • Chronic Disease
  • Disease Models, Animal*
  • Electroencephalography
  • Female
  • Heart Arrest, Induced / adverse effects*
  • Hemofiltration / methods*
  • Hypothermia, Induced / adverse effects*
  • Inflammation
  • Interleukin-1 / blood
  • Interleukin-8 / blood
  • Leukocyte Count
  • Leukocytes / immunology*
  • Morbidity
  • Nerve Growth Factors / blood
  • Random Allocation
  • Reperfusion Injury / blood
  • Reperfusion Injury / etiology*
  • Reperfusion Injury / mortality
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins*
  • Severity of Illness Index
  • Swine
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Calcium-Binding Proteins
  • Interleukin-1
  • Interleukin-8
  • Nerve Growth Factors
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins
  • Tumor Necrosis Factor-alpha