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

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

Author information

1
1] Pediatric Intensive Care Unit, The Royal Children's Hospital, Melbourne, Australia [2] Murdoch Children's Research Institute, Melbourne, Australia.
2
1] Murdoch Children's Research Institute, Melbourne, Australia [2] Department of Paediatrics, University of Melbourne, Melbourne, Australia.
3
Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, Australia.
4
Department of Radiology, The Royal Children's Hospital, Melbourne, Australia.
5
Cardiac Surgery, The Royal Children's Hospital, Melbourne, Australia.
6
1] Murdoch Children's Research Institute, Melbourne, Australia [2] Department of Paediatrics, University of Melbourne, Melbourne, Australia [3] Cardiac Surgery, The Royal Children's Hospital, Melbourne, Australia.
7
Section of Cardiology, Texas Children's Hospital, Houston, Texas.
8
Section of Critical Care Medicine, Texas Children's Hospital, Houston, Texas.

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.

PMID:
24713816
DOI:
10.1038/pr.2014.51
[Indexed for MEDLINE]

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