Blood-brain barrier integrity in a rat model of emergency preservation and resuscitation

Emergency Preservation and Resuscitation (EPR) represents a novel approach to treat exsanguination cardiac arrest (CA) victims, using an aortic flush to induce hypothermia during circulatory arrest, followed by delayed resuscitation with cardiopulmonary bypass (CPB). The status of the blood-brain barrier (BBB) integrity after prolonged hypothermic CA is unclear. The objective of this study was to assess BBB permeability in two EPR models in rats, associated with poor outcome. Rats subjected to traumatic brain injury (TBI) and naïve rats served as positive and negative controls, respectively.

The BBB will be disrupted after TBI, but intact after prolonged hypothermic CA.

Four groups were studied: (1) EPR-IC (ice cold)-75 min CA at 15 degrees C; (2) EPR-RT (room temperature)-20 min CA at 28 degrees C; (3) TBI; (4) sham. Rats in EPR groups were subjected to rapid hemorrhage, followed by CA. Rats in the TBI group had a controlled cortical impact to the left hemisphere. Naïves were subjected to the same anesthesia and surgery. 1h after insult, rats were injected with Evans Blue (EB), a marker of BBB permeability for albumin. Rats were sacrificed after 5h and EB absorbance was quantified in brain samples.

TBI produced an approximately 10-fold increase in EB absorbance in the left (injured) hemisphere vs. left hemisphere for all other groups (p=0.001). In contrast, EB absorbance in either EPR group did not differ from sham.

BBB integrity to albumin is not disrupted early after resuscitation from prolonged CA treated with EPR. Neuroprotective adjuncts to hypothermia in this setting should focus on agents that penetrate the BBB. These findings also have implications for deep hypothermic circulatory arrest.