Exploration of pharmacologic aortic arch flush strategies for rapid induction of suspended animation (SA) (cerebral preservation) during exsanguination cardiac arrest (ExCA) of 20 min in dogs

Objectives: ExCA can rarely be survived by conventional resuscitation attempts. This is an overview of systematic explorations of methods for rapid initiation of SA (preservation for transport and resuscitative surgery) with mild hypothermic aortic arch flush. We hypothesized that flush with drugs at start of 20 min ExCA, can achieve normal functional recovery, as did saline flush at 4°C without drug. Methods: 43 dogs (20-25 kg) were exsanguinated over 5 min to CA of 20 min no-flow, resuscitated by closed-chest cardiopulmonary bypass. Controlled ventilation was to 20 h, and intensive care to 72 h. At CA 2 min, the dogs received a flush of 500 ml saline at 24°C into the aortic arch via a balloon catheter. Added to the flush were drugs for different strategies: delaying energy failure (2Chloroadenosine [Ad], Thiopental [Th], Fructose-Bi-Phosphate [FBP]); protecting membrane integrity (MK801; Nimodipine; Phenytoin with Th [Ph/Th]); preventing apoptosis (Cycloheximide [Cyclo]); blocking intracellular Ca²⁺ (Ca²⁺ calmodulin antagonist [W-7]). Results: See table. Overall performance category (OPC) 1 (normal function at 72 h) was achieved only by 2 dogs with Th and 1 dog with Ph/Th. Neurologic deficit score (NDS) 0-10%=normal, 100%=brain death. Brain histologic damage scores will be presented. Conclusion: Seeking a breakthrough effect - consistant normal recovery (OPC 1)- was not achieved with any of these pharmacologie approaches. Combination treatments of drues with relatively "better" outcomes should be tested. Control Ad Th FBP MK801 Nimod Ph/Th Cyclo W-7 OPC 1 0/7 0/2 2/9 0/5 0/5 0/2 1/7 0/3 0/2 NDS(%) 56 50,43 52 55 50 33,66 55 50,39, 66,48 (29-65) (22-57) (39-63) (33-55) (38-59) 42 OPC data are given as n with good outcome from n total. NDS data are given as single values or median (interquartile range).