Impact of levosimendan on brain injury patterns in a lamb model of infant cardiopulmonary bypass

Pediatr Res. 2014 Jul;76(1):64-71. doi: 10.1038/pr.2014.51. Epub 2014 Apr 8.

Abstract

Background: The effects of levosimendan (Levo) on injury patterns in the immature brain following cardiopulmonary bypass (CPB) are unknown.

Methods: Eighteen 3- to 4-wk-old anesthetized lambs, instrumented with vascular catheters and aortic and right carotid artery flow probes, were allocated to non-CPB, CPB, or CPB+Levo groups (each n = 6). After 120 min CPB with 90 min aortic cross-clamp, CPB animals received dopamine, and CPB+Levo animals both dopamine and Levo, for 4 h. All lambs then underwent brain magnetic resonance imaging, followed by postmortem brain perfusion fixation for immunohistochemical studies.

Results: In CPB lambs, aortic (P < 0.05) and carotid artery (P < 0.01) blood flows fell by 29 and 30%, respectively, between 2 and 4 h after cross-clamp removal but were unchanged in the CPB+Levo group. No brain injury was detectable with magnetic resonance imaging in either CPB or CPB+Levo lambs. However, on immunohistochemical analysis, white matter astrocyte density of both groups was higher than in non-CPB lambs (P < 0.05), while white matter microglial density was higher (P < 0.05), but markers of cortical oxidative stress were less prevalent in CPB+Levo than CPB lambs.

Conclusion: While Levo prevented early postoperative falls in cardiac output and carotid artery blood flow in a lamb model of infant CPB, this was associated with heterogeneous neuroglial activation and manifestation of markers of oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / therapeutic use
  • Blood Gas Analysis
  • Brain / drug effects
  • Brain / pathology
  • Brain Injuries / drug therapy*
  • Cardiac Output / drug effects
  • Cardiopulmonary Bypass / adverse effects*
  • Cardiopulmonary Bypass / methods
  • Carotid Arteries / drug effects
  • Disease Models, Animal
  • Dopamine / chemistry
  • Hemodynamics / drug effects
  • Hydrazones / therapeutic use*
  • Immunohistochemistry
  • Magnetic Resonance Imaging
  • Neuroglia / drug effects
  • Oxidative Stress
  • Pyridazines / therapeutic use*
  • Sheep
  • Simendan

Substances

  • Anti-Arrhythmia Agents
  • Hydrazones
  • Pyridazines
  • Simendan
  • Dopamine