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J Thorac Cardiovasc Surg 2006;131:659-665
© 2006 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Antegrade cerebral perfusion reduces apoptotic neuronal injury in a neonatal piglet model of cardiopulmonary bypass

Valerie Y. Chock, MD a , * , Gabriel Amir, MD b , Corrine R. Davis, PhD c , Chandra Ramamoorthy, MD d , R. Kirk Riemer, PhD b , Dustin Ray d , Rona G. Giffard, MD, PhD d , V. Mohan Reddy, MD b

a Department of Neonatology, Stanford University School of Medicine, Stanford, Calif
b Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, Calif
c Department of Comparative Medicine, Stanford University School of Medicine, Stanford, Calif
d Department of Anesthesia, Stanford University School of Medicine, Stanford, Calif

Received for publication May 23, 2005; revisions received September 2, 2005; accepted for publication September 13, 2005.

* Address for reprints: Valerie Chock, MD, Division of Neonatology, Stanford University Medical Center, 750 Welch Rd, Suite 315, Stanford, CA 94305. (Email: vchock{at}stanford.edu).

OBJECTIVE: Neonates with congenital heart disease might require surgical repair with deep hypothermic circulatory arrest, a technique associated with adverse neurodevelopmental outcomes. Antegrade cerebral perfusion is thought to minimize ischemic brain injury, although there are no supporting experimental data. We sought to evaluate and compare the extent of neurologic injury in a neonatal piglet model of deep hypothermic circulatory arrest and antegrade cerebral perfusion.

METHODS: Neonatal piglets undergoing cardiopulmonary bypass were randomized to deep hypothermic circulatory arrest or antegrade cerebral perfusion for 45 minutes. Animals were killed after 6 hours of recovery, and brain tissue was stained for evidence of cellular injury and for the apoptotic markers activated caspase 3 and cytochrome c translocation from mitochondria to cytosol.

RESULTS: Piglets from the antegrade cerebral perfusion group exhibited less apoptotic or necrotic injury (4 ± 3 vs 29 ± 12 cells per field, P = .03). The piglets undergoing antegrade cerebral perfusion also had less evidence of apoptosis, with fewer cells staining for activated caspase 3 (57 ± 8 vs 93 ± 9 cells per field, P = .001) or showing cytochrome c translocation (6 ± 2 vs 15 ± 4 cells per field, P = .02).

CONCLUSIONS: The use of antegrade cerebral perfusion in place of deep hypothermic circulatory arrest reduces evidence of apoptosis and histologic injury in neonatal piglets. Neonates with congenital heart disease might benefit from antegrade cerebral perfusion during complex cardiac surgery to improve their overall neurologic outcome.

Abbreviations and Acronyms ACP = antegrade cerebral perfusion; CPB = cardiopulmonary bypass; CREB = cAMP response element binding protein; DHCA = deep hypothermic circulatory arrest; H&E = hematoxylin and eosin; NMDA = N-methyl-D-aspartate; TUNEL = terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling




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[Abstract] [Full Text] [PDF]


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