Abstract 16872: Levosimendan Modulates Brain Injury Pattern in a Model of Infant Cardiopulmonary Bypass
Introduction. Brain immaturity and cardiopulmonary bypass (CPB) are important factors in the pathophysiology of brain injury in infants undergoing cardiac surgery. However, the impact of Levosimendan (Levo), a novel inodilator, on circulatory hemodynamics and microscopic markers of brain injury have not been fully investigated. We therefore studied the effects of Levo on global and regional hemodynamics and brain immunohistochemistry in a lamb model of infant CPB.
Methods. Eighteen 1-week-old and eighteen 4-week lambs were anesthetized and instrumented with vascular catheters and aortic and right carotid artery transit-time flow probes. At each age, similar numbers were allocated to one of three treatment groups: 1) Non-CPB control, 2) CPB and 3) CPB+Levo. CPB animals underwent aortic and right atrial cannulation, and all received 120 min of CPB, with 90 min of aortic cross-clamp (XC) and cardioplegic arrest. Lambs in Group 2 received dopamine, and in Group 3, dopamine plus Levo, on weaning from CPB. Hemodynamic measurements were recorded pre-CPB and at 60, 120, 180 and 240 min after XC removal. At the end of the study, brains were fixed by perfusion and prepared for immunohistochemical analysis. Data were analysed with analysis of variance and P<0.05 considered significant.
Results. After CPB in 1-week lambs, cardiac output fell by 25% (P<0.05) and carotid artery flow by 45% (P<0.05), while in the CPB+Levo group, cardiac output was preserved and carotid artery flow fell by 23% (P<0.05). After CPB in 4-week lambs, cardiac output decreased by 26% (P<0.05) and carotid artery flow by 32% (P<0.05), but in the CPB+Levo group, both cardiac output and carotid artery flow were preserved. On brain immunohistochemistry, an increased density of microglia (P<0.05) was evident in deep white matter of the CPB+Levo group in 4-week, but not 1-week lambs.
Conclusion. In a model of infant CPB, Levo prevented an early post-operative fall in cardiac output after CPB. However, while Levo preserved post-CPB carotid artery blood flow in 4-week lambs, this was associated with microscopic changes suggestive of increased brain injury. The impact of Levo on cerebral hemodynamics and evolution of brain injury in the immature circulation after CPB warrants further investigation.
- © 2011 by American Heart Association, Inc.