Cerebral mitochondrial dysfunction associated with deep hypothermic circulatory arrest in neonatal swine

被引:33
作者
Mavroudis, Constantine D. [1 ]
Karlsson, Michael [2 ]
Ko, Tiffany [3 ]
Hefti, Marco [4 ]
Gentile, Javier I. [1 ]
Morgan, Ryan W. [2 ]
Plyler, Ross [2 ]
Mensah-Brown, Kobina G. [3 ]
Boorady, Timothy W. [3 ]
Melchior, Richard W. [5 ]
Rosenthal, Tami M. [5 ]
Shade, Brandon C. [5 ]
Schiavo, Kellie L. [5 ]
Nicolson, Susan C. [2 ]
Spray, Thomas L. [1 ]
Sutton, Robert M. [2 ]
Berg, Robert A. [2 ]
Licht, Daniel J. [3 ]
Gaynor, J. William [1 ]
Kilbaugh, Todd J. [2 ]
机构
[1] Childrens Hosp Philadelphia, Dept Cardiothorac Surg, Philadelphia, PA 19104 USA
[2] Childrens Hosp Philadelphia, Dept Anesthesia & Crit Care Med, Philadelphia, PA 19104 USA
[3] Childrens Hosp Philadelphia, Dept Neurol, Philadelphia, PA 19104 USA
[4] Univ Iowa, Dept Pathol, Carver Coll Med, Iowa City, IA 52242 USA
[5] Childrens Hosp Philadelphia, Dept Perfus Serv, Philadelphia, PA 19104 USA
关键词
Deep hypothermic circulatory arrest; Congenital heart surgery; Neuroprotection; Mitochondria; Basic science; CARDIAC-ARREST; PH MANAGEMENT; BRAIN-INJURY; ALPHA-STAT; BLOOD-FLOW; PERFUSION; MODEL; MICROCIRCULATION; RESUSCITATION; METABOLISM;
D O I
10.1093/ejcts/ezx467
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVES: Controversy remains regarding the use of deep hypothermic circulatory arrest (DHCA) in neonatal cardiac surgery. Alterations in cerebral mitochondrial bioenergetics are thought to contribute to ischaemia-reperfusion injury in DHCA. The purpose of this study was to compare cerebral mitochondrial bioenergetics for DHCA with deep hypothermic continuous perfusion using a neonatal swine model. METHODS: Twenty-four piglets (mean weight 3.8 kg) were placed on cardiopulmonary bypass (CPB): 10 underwent 40-min DHCA, following cooling to 18 degrees C, 10 underwent 40 min DHCA and 10 remained at deep hypothermia for 40 min; animals were subsequently rewarmed to normothermia. 4 remained on normothermic CPB throughout. Fresh brain tissue was harvested while on CPB and assessed for mitochondrial respiration and reactive oxygen species generation. Cerebral microdialysis samples were collected throughout the analysis. RESULTS: DHCA animals had significantly decreased mitochondrial complex I respiration, maximal oxidative phosphorylation, respiratory control ratio and significantly increased mitochondrial reactive oxygen species (P < 0.05 for all). DHCA animals also had significantly increased cerebral microdialysis indicators of cerebral ischaemia (lactate/pyruvate ratio) and neuronal death (glycerol) during and after rewarming. CONCLUSIONS: DHCA is associated with disruption of mitochondrial bioenergetics compared with deep hypothermic continuous perfusion. Preserving mitochondrial health may mitigate brain injury in cardiac surgical patients. Further studies are needed to better understand the mechanisms of neurological injury in neonatal cardiac surgery and correlate mitochondrial dysfunction with neurological outcomes.
引用
收藏
页码:162 / 168
页数:7
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