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


CONCLUSIONS
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.
1] Pediatric Intensive Care Unit, The Royal Children's Hospital, Melbourne, Australia [2] Murdoch Children's Research Institute, Melbourne, Australia.
Poongundran
P
Namachivayam
1] Murdoch Children's Research Institute, Melbourne, Australia [2] Department of Paediatrics, University of Melbourne, Melbourne, Australia.
Joseph J
JJ
Smolich
Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, Australia.
Amy E
AE
Shields
Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, Australia.
Sandra
S
Rees
Department of Radiology, The Royal Children's Hospital, Melbourne, Australia.
Lee
L
Coleman
Cardiac Surgery, The Royal Children's Hospital, Melbourne, Australia.
Steven B
SB
Horton
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.
Igor E
IE
Konstantinov
Section of Cardiology, Texas Children's Hospital, Houston, Texas.
Daniel J
DJ
Penny
Section of Critical Care Medicine, Texas Children's Hospital, Houston, Texas.
Lara S
LS
Shekerdemian
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001784:Blood Gas Analysis; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy*; D002302:Cardiac Output / Q000187:drug effects; D002315:Cardiopulmonary Bypass / Q000009:adverse effects* / Q000379:methods; D002339:Carotid Arteries / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000737:chemistry; D006439:Hemodynamics / Q000187:drug effects; D006835:Hydrazones / Q000627:therapeutic use*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D009457:Neuroglia / Q000187:drug effects; D018384:Oxidative Stress; D011724:Pyridazines / Q000627:therapeutic use*; D012756:Sheep; D000077464:Simendan
D000889:Anti-Arrhythmia Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan; D004298:Dopamine