Abstract 73: Lipid Mediators as Novel Biomarkers and Surrogate Indicators of Neurologic Recovery after Cardiac Arrest in a Hypothermic Swine Model
Background: Prognostic tools to predict neurologic outcome are essential so that relevant care can be given to patients awakening from coma, and futile intensive care be avoided in patients with severe hypoxic ischemic encephalopathy. There is a need for biomarkers as surrogate indicators of ischemic brain injury or recovery. We studied lipid mediators (Neuroprotectin D1, (NPD1), DHA, PGE-2, and PGD-2) that would reflect the status of anti-inflammatory signaling in endothelial cells and/or brain parenchyma.
Methods: Swine who had return of spontaneous circulation (ROSC) after cardiac arrest, with CPR, and up to 3 shocks were randomized to receive 20 hours of hypothermia with Life Recovery Systems (LRS) Thermosuitâ,,¢ at 34Â° C (n=6) or as normothermic controls (n = 8). Serial blood samples were obtained at intervals up to 48 hrs.
Results: The time required to reach the target cooling temperature was 9.0 min. Normal neurologic function was regained in all 6 hypothermic animals but in only 1 of 8 normothermic animals. At 3 hours after ROSC, NPD1 rose from 2– 4 pmole/ml to 16 pmole/ml in normothermic controls and remarkably to 50 pmole/ml (p < 0.0034) in hypothermic pigs. DHA, the precursor of NPD1, and arachidonic acid showed two distinct peaks only in hypothermic animals, one immediately following ROSC and a second higher peak at 12 hrs. Prostaglandins E2 and D2 were not different between the groups.
Conclusion: We found differential patterns of changes in lipid mediators as a function of time after cardiac arrest. NPD1 displayed a remarkable increase only in the hypothermic animals who also displayed uniform recovery of normal neurologic function. These changes followed a course totally independent of the other lipid mediators studied. Changes in NPD1 may reflect activation of cytoprotective and neuroprotective anti-inflammatory cell signalling in endothelial cells and/or brain parenchyma, correlating well with hypothermia-induced functional recovery.