Cerebral activation of mitogen-activated protein kinases after circulatory arrest and low flow cardiopulmonary bypass

Alon S. Aharon, Matthew R. Mulloy, Davis C. Drinkwater, Oliver B. Lao, Mahlon Johnson, Megan Thunder, Chang Yu, Paul Chang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objectives: Mitogen-activated protein kinases (MAPK) are important intermediates in the signal transduction pathways involved in neuronal dysfunction following cerebral ischemia-reperfusion injury. One subfamily, extracellular regulated kinase 1/2, has been heavily implicated in the pathogenesis of post-ischemic neuronal damage. However, the contribution of extracellular regulated kinase 1/2 to neuronal damage following deep hypothermic circulatory arrest and low flow cardiopulmonary bypass is unknown. We attempted to correlate the extent of neuronal damage present following deep hypothermic circulatory arrest and low flow cardiopulmonary bypass with phosphorylated extracellular regulated kinase 1/2 expression in the cerebral vascular endothelium. Methods: Piglets underwent normal flow cardiopulmonary bypass (n=4), deep hypothermic circulatory arrest (n=6) and low flow cardiopulmonary bypass (n=5). Brains were harvested following 24 h of post-cardiopulmonary bypass recovery. Cerebral cortical watershed zones, hippocampus, basal ganglia, thalamus, cerebellum, mesencephalon, pons and medulla were evaluated using hematoxylin and eosin staining. A section of ischemic cortex was evaluated by immunohistochemistry with rabbit polyclonal antibodies against phosphorylated extracellular regulated kinase 1/2. Results: Compared to cardiopulmonary bypass controls, the deep hypothermic circulatory arrest and low flow cardiopulmonary bypass piglets exhibited diffuse ischemic changes with overlapping severity and distribution. Significant neuronal damage occurred in the frontal watershed zones and basal ganglia of the deep hypothermic circulatory arrest group (P<0.05). No detectable phosphorylated extracellular regulated kinase 1/2 immunoreactivity was found in the cardiopulmonary bypass controls; however, ERK 1/2 immunoreactivity was present in the cerebral vascular endothelium of the deep hypothermic circulatory arrest and low flow cardiopulmonary bypass groups. Conclusions: Our results indicate that phosphorylated extracellular regulated kinase 1/2 may play a prominent role in early cerebral ischemia-reperfusion injury and endothelial dysfunction. The pharmacologic inhibition of extracellular regulated kinase 1/2 represents a new and exciting opportunity for the modulation of cerebral tolerance to low flow cardiopulmonary bypass and deep hypothermic circulatory arrest.

Original languageEnglish (US)
Pages (from-to)912-919
Number of pages8
JournalEuropean Journal of Cardio-thoracic Surgery
Volume26
Issue number5
DOIs
StatePublished - Nov 1 2004
Externally publishedYes

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Deep Hypothermia Induced Circulatory Arrest
Mitogen-Activated Protein Kinases
Cardiopulmonary Bypass
Phosphotransferases
Vascular Endothelium
Basal Ganglia
Reperfusion Injury
Brain Ischemia
Pons
Hematoxylin
Eosine Yellowish-(YS)
Mesencephalon
Thalamus
Cerebellum
Signal Transduction
Hippocampus
Immunohistochemistry
Staining and Labeling
Rabbits
Antibodies

All Science Journal Classification (ASJC) codes

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Cerebral activation of mitogen-activated protein kinases after circulatory arrest and low flow cardiopulmonary bypass. / Aharon, Alon S.; Mulloy, Matthew R.; Drinkwater, Davis C.; Lao, Oliver B.; Johnson, Mahlon; Thunder, Megan; Yu, Chang; Chang, Paul.

In: European Journal of Cardio-thoracic Surgery, Vol. 26, No. 5, 01.11.2004, p. 912-919.

Research output: Contribution to journalArticle

Aharon, Alon S. ; Mulloy, Matthew R. ; Drinkwater, Davis C. ; Lao, Oliver B. ; Johnson, Mahlon ; Thunder, Megan ; Yu, Chang ; Chang, Paul. / Cerebral activation of mitogen-activated protein kinases after circulatory arrest and low flow cardiopulmonary bypass. In: European Journal of Cardio-thoracic Surgery. 2004 ; Vol. 26, No. 5. pp. 912-919.
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AU - Johnson, Mahlon

AU - Thunder, Megan

AU - Yu, Chang

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