Abstract P37: Blood Brain Barrier Integrity in Emergency Preservation and Resuscitation Rat Model
Emergency Preservation and Resuscitation (EPR) is a novel approach to treat exsanguination cardiac arrest (ExCA) victims, using an aortic flush to induce hypothermia during circulatory arrest(CA), followed by delayed resuscitation with cardiopulmonary bypass (CPB). The status of blood brain barrier (BBB) integrity after prolonged hypothermic CA is unclear and controversial. In contrast, BBB disruption is well-recognized after traumatic brain injury (TBI).
The objective of this study was to assess BBB permeability in two EPR models in rats, associated with poor outcome. TBI and naïve rats served as positive and negative controls respectively.
Hypothesis: BBB will be disrupted after TBI, but intact after prolonged hypothermic CA.
Methods: Using Isoflurane anesthetized adult male Sprague-Dawley rats, 4 groups were studied using EPR with either an ice cold (IC) or room temperature (RT) flush:
EPR-IC-75 min CA at 15°C (n=3);
EPR-RT-20 min CA at 28°C (n=4);
Rats in the EPR groups were subjected to rapid hemorrhage, followed by CA. In the EPR-IC group, hypothermia was initiated after 1 min of no-flow using IC flush, target 15°C for a 75 min CA. In the EPR-RT group, hypothermia (28°C) was induced after 5 min delay, with a 20 min CA. Resuscitation was initiated with CPB. Rats in the TBI group had a controlled cortical impact to the right hemisphere. Naives were subjected to the same anesthesia and surgery. After CPB, rats were injected IV with Evans Blue (EB), a BBB marker, for 5 h. and EB quantified in brain samples.
Results: TBI produced an ~10 fold increase in EB absorbance in the right (injured) hemisphere at 5h vs right hemispheres of all other groups (p=0.001), and a more modest increase in the L (uninjured) hemisphere vs. EPR-IC or EPR-RT groups (p<0.05). In contrast, EB absorbance in either EPR group did not differ from naïve.
Discusssion: BBB integrity to albumin is not disrupted early after resuscitation from prolonged CA treated with moderate or deep hypothermic EPR. Future studies should assess if BBB is permeable either to smaller molecules or in a delayed fashion.
Conclusion: Resuscitation from ExCA with EPR and deep hypothermia does not damage BBB. Neuroprotective adjuncts to hypothermia should focus on agents that penetrate the BBB.