title: Adenosine by aortic flush fails to augment the brain preservation effect of mild hypothermia during exsanguination cardiac arrest in dogs - an exploratory study.
abstract: Most trauma cases with rapid exsanguination to cardiac arrest (CA) in the field, as well as many cases of normovolemic sudden cardiac death are 'unresuscitable' by standard cardiopulmonary-cerebral resuscitation (CPCR). We are presenting a dog model for exploring pharmacological strategies for the rapid induction by aortic arch flush of suspended animation (SA), i.e. preservation of cerebral viability for 15 min or longer. This can be extended by profound hypothermic circulatory arrest of at least 60 min, induced and reversed with (portable) cardiopulmonary bypass (CPB). SA is meant to buy time for transport and repair during pulselessness, to be followed by delayed resuscitation to survival without brain damage. This model with exsanguination over 5 min to CA of 15-min no-flow, is to evaluate rapid SA induction by aortic flush of normal saline solution (NSS) at room temperature (24 degrees C) at 2-min no-flow. This previously achieved normal functional recovery, but with histologic brain damage. We hypothesized that the addition of adenosine would achieve recovery with no histologic damage, because adenosine delays energy failure and helps repair brain injury. This dog model included reversal of 15-min no-flow with closed-chest CPB, controlled ventilation to 20 h, and intensive care to 72 h. Outcome was evaluated by overall performance, 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 heart via an aortic balloon catheter. Controls (n=5) received no drug. The adenosine group (n=5) received 2-chloro-adenosine (long acting adenosine analogue), 30 mg in the flush solution, and, after reperfusion, adenosine i.v. over 12 h (210 microg/kg per min for 3 h, 140 microg/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 approximately 36.0 degrees C in both groups. At 72 h, final overall performance category (OPC) 1 (normal) was achieved by all ten dogs of the two groups. Final neurologic deficit scores (NDS; 0-10% normal, 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 prevalent in the basal ganglia and neocortex as in the cerebellum and hippocampus. The mild hypothermic aortic flush protocol is feasible in dogs. The adenosine strategy used does not abolish the mild histologic brain damage.
authors.affiliation: Safar Center for Resuscitation Research and the Department of Anesthesiology/Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Woods
authors.forename: S
authors.initials: S
authors.lastname: Prueckner
authors.forename: P
authors.initials: P
authors.lastname: Safar
authors.forename: A
authors.initials: A
authors.lastname: Takasu
authors.forename: S A
authors.initials: SA
authors.lastname: Tisherman
authors.forename: E K
authors.initials: EK
authors.lastname: Jackson
authors.forename: A
authors.initials: A
authors.lastname: Radovsky
authors.forename: P
authors.initials: P
authors.lastname: Kochanek
authors.forename: W
authors.initials: W
authors.lastname: Behringer
authors.forename: S W
authors.initials: SW
authors.lastname: Stezoski
authors.forename: R
authors.initials: R
authors.lastname: Hans
mesh_terms: D000241:Adenosine / Q000008:administration & dosage*; D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004285:Dogs; D006323:Heart Arrest / Q000188:drug therapy* / Q000401:mortality; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007036:Hypothermia, Induced; D007261:Infusions, Intra-Arterial; D008297:Male; D012016:Reference Values; D012771:Shock, Hemorrhagic; D015996:Survival Rate; D014665:Vasodilator Agents / Q000008:administration & dosage*
chemical_list: D014665:Vasodilator Agents; D000241:Adenosine