Examination of physiological function and biochemical disorders in a rat model of prolonged asphyxia-induced cardiac arrest followed by cardio pulmonary bypass resuscitation.
BACKGROUND
Cardiac arrest induces whole body ischemia, which causes damage to multiple organs particularly the heart and the brain. There is clinical and preclinical evidence that neurological injury is responsible for high mortality and morbidity of patients even after successful cardiopulmonary resuscitation. A better understanding of the metabolic alterations in the brain during ischemia will enable the development of better targeted resuscitation protocols that repair the ischemic damage and minimize the additional damage caused by reperfusion.


METHODS
A validated whole body model of rodent arrest followed by resuscitation was utilized; animals were randomized into three groups: control, 30 minute asphyxial arrest, or 30 minutes asphyxial arrest followed by 60 min cardiopulmonary bypass (CPB) resuscitation. Blood gases and hemodynamics were monitored during the procedures. An untargeted metabolic survey of heart and brain tissues following cardiac arrest and after CPB resuscitation was conducted to better define the alterations associated with each condition.


RESULTS
After 30 min cardiac arrest and 60 min CPB, the rats exhibited no observable brain function and weakened heart function in a physiological assessment. Heart and brain tissues harvested following 30 min ischemia had significant changes in the concentration of metabolites in lipid and carbohydrate metabolism. In addition, the brain had increased lysophospholipid content. CPB resuscitation significantly normalized metabolite concentrations in the heart tissue, but not in the brain tissue.


CONCLUSIONS
The observation that metabolic alterations are seen primarily during cardiac arrest suggests that the events of ischemia are the major cause of neurological damage in our rat model of asphyxia-CPB resuscitation. Impaired glycolysis and increased lysophospholipids observed only in the brain suggest that altered energy metabolism and phospholipid degradation may be a central mechanism in unresuscitatable brain damage.
Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Junhwan
J
Kim
Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Tai
T
Yin
Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Ming
M
Yin
Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Wei
W
Zhang
Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Koichiro
K
Shinozaki
Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Mary A
MA
Selak
Metabolon Inc., Durham, North Carolina, United States of America.
Kirk L
KL
Pappan
Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Joshua W
JW
Lampe
Center for Resuscitation Science, Department of Emergency Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Lance B
LB
Becker
D000818:Animals; D001237:Asphyxia / Q000150:complications*; D001784:Blood Gas Analysis; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D016887:Cardiopulmonary Resuscitation / Q000009:adverse effects*; D005227:Fatty Acids / Q000378:metabolism; D006019:Glycolysis; D006321:Heart / Q000503:physiopathology; D006323:Heart Arrest / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy*; D008297:Male; D055432:Metabolomics; D017202:Myocardial Ischemia / Q000209:etiology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley
D005227:Fatty Acids