Abstract 199: Neurological Recovery “Life after Death” following Total Brain Ischemia with Controlled Reperfusion
Brain damage due to limited ischemic tolerance often precludes meaningful recovery from sudden death, despite cardiac salvage. This study tests the tolerance of 30 minutes of normothermic (37°C) total brain ischemia in pigs using a new isolated global ischemic brain model that simulates sudden death. We tested how regular blood (uncontrolled reperfusion) or controlled reperfusion (controlling the conditions and composition of the reperfusate) influences neurological recovery.
Methods: Following 30 minutes of global brain ischemia, 12 pigs received either uncontrolled reperfusion with regular blood (n=6), or controlled reperfusion (n=6) by infusing a warm (hypocalcemic, hypermagnesemic, hyperosmolar, alkalotic, substrate enriched) modified blood solution delivered through a WBC filter for 20 minutes. Neurologic deficit score (NDS) evaluated respiration, cranial nerves, motor and sensory, behavior, and consciousness (score 0=normal, 500=brain death) 24 hours after reperfusion.
Results: Normal blood reperfusion caused negligible brain O2 uptake (2 extraction)* indicating damaged mitochondria, oxidant damage with raised conjugated dienes (CD) levels (1.64±0.02 A233mn)*, multiple post reperfusion seizures, 2 early deaths by brain herniation, and high NDS (231±16 in survivors)*. Post mortem analysis included marked tissue edema (83.6±0.6%)* with extensive basal ganglia and distal cortical infarcts measured by TTC stain*. In contrast, all 6 controlled reperfusion pigs had high O2 uptake, low CD levels (1.3±0.03 A233mn), awakened promptly to sit and eat, no seizures, and a low 24 hour NDS (39±16), with 3 showing complete recovery (NDS=0). Brain edema was low (81.1±0.2), and TTC stain showed no infarction.
Conclusions: Controlled reperfusion allows near complete neurologic recovery offsetting the presumed irreversible damage after 30-min warm global brain ischemia. This therapy redefines the time of brain death, and introduces potential innovative applications for a novel new treatment for brain ischemia after sudden death and stoke. *p<0.05 group controlled vs. uncontrolled, mean±SE