Adenosine by aortic flush fails to augment the brain preservation effect of mild hypothermia during exsanguination cardiac arrest in dogs - an exploratory study

Most trauma cases with rapid exsanguination to cardiac arrest (CA) in the f ield, as well as many cases of normovolemic sudden cardiac death are 'unres uscitable' by standard cardiopulmonary-cerebral resuscitation (CPCR). We ar e presenting a dog model for exploring pharmacological strategies for the s apid induction by aortic arch flush of suspended animation (SA), i.e. prese rvation of cerebral viability for 15 min or longer. This can be extended by profound hypothermic circulatory arrest of at least 60 min, induced and re versed with (portable) cardiopulmonary bypass (CPB). SA is meant to buy tim e for transport and repair during pulselessness, to be followed by delayed resuscitation to survival without brain damage. This model with exsanguinat ion over 5 min to CA of 15-min no-flow, is to evaluate rapid SA induction b y aortic flush of normal saline solution (NSS) at room temperature (24 degr ees C) at 2-min no-flow. This previously achieved normal functional recover y, but with histologic brain damage. We hypothesized that the addition of a denosine would achieve recovery with no histologic damage, because adenosin e delays energy failure and helps repair brain injury. This dog model inclu ded reversal of 15-min no-flow with closed-chest CPB, controlled ventilatio n to 20 h, and intensive care to 72 h. outcome was evaluated by overall per formance, neurologic deficit, and brain histologic damage. At 2 min of CA, 500 ml of NSS at 24 degrees C was flushed (over 1 min) into the brain and h eart via an aortic balloon catheter. Controls (n = 5) received no drug. The adenosine group (n = 5) received 2-chloro-adenosine (Pong acting adenosine analogue), 30 mg in the flush solution, and, after reperfusion, adenosine i.v. over 12 h (210 mu g/kg per min for 3 h, 140 mu g/kg per min for 9 h). The 24 degrees C flush reduced tympanic membrane temperature (T-ty) within 2 min of CA from 37.5 to approximate to 36.0 degrees C in both groups. At 7 2 h, final overall performance category (OPC) 1 (normal) was achieved by al l ten dogs of the two groups. Final neurologic deficit scores (NDS; 0-10% n ormal, 100% brain death) were 5 +/- 3% in the control group versus 6 +/- 5% in the adenosine group (NS). Total brain histologic damage scores (HDS) at 72 h were 74+/-9 (64-80) in the control group versus 68 +/- 19 (40-88) in the adenosine group (NS). In both groups, ischemic neurons were as prevalen t in the basal ganglia and neocortex as in the cerebellum and hippocampus. The mild hypothermic aortic flush protocol is feasible in dogs. The adenosi ne strategy used does not abolish the mild histologic brain damage. (C) 200 0 Elsevier Science Ireland Ltd. All rights reserved.