title: Exsanguination cardiac arrest in rats treated by 60 min, but not 75 min, emergency preservation and delayed resuscitation is associated with intact outcome.
abstract: Emergency preservation and resuscitation (EPR) is a new approach for resuscitation of exsanguination cardiac arrest (CA) victims to buy time for surgical hemostasis. EPR uses a cold aortic flush to induce deep hypothermic preservation, followed by resuscitation with cardiopulmonary bypass (CPB). We previously reported that 20 min of EPR was feasible with intact outcome. In this report, we tested the limits for EPR in rats. Adult male isoflurane-anesthetized rats were subjected to rapid hemorrhage (12.5 ml over 5 min), followed by esmolol/KCl-induced CA and 1 min of no-flow. EPR was then induced by perfusion with 270 ml of ice-cold Plasma-Lyte to decrease body temperature to 15 degrees C. After 60 min (n=7) or 75 min (n=7) of EPR, resuscitation was attempted with CPB over 60 min, blood transfusion, correction of acid-base balance and electrolyte disturbances, and mechanical ventilation for 2h. Survival, overall performance category (OPC: 1=normal, 5=death), neurological deficit score (NDS), and histological damage score (HDS) were assessed in survivors on day 3. While all rats after 60 min EPR survived, only two out of seven rats after 75 min EPR survived (p<0.05). All rats after 60 min EPR achieved OPC 1 and normal NDS by day 3. Survivors after 75 min EPR achieved best OPC 3 (p<0.05 vs. 60 min EPR). HDS of either brain or individual viscera was not statistically different after 60 versus 75 min EPR, except for kidneys (0+/-0 vs. 1.9+/-1.3, respectively; p<0.05), with a strong trend toward greater injury in all extracerebral organs in the 75-min EPR group (p<0.06). Histological findings were dominated by cardiac lesions observed in both groups and acute renal tubular and liver necrosis in the 75-min EPR group. In conclusion, we have shown that 60 min of EPR after exsanguination CA is associated with survival and favorable neurological outcome, while 75 min of EPR results in significant mortality and neurological damage in survivors. Surprisingly, extracerebral lesions predominated at 75-min EPR group. This model should serve as a screening model both for testing new pharmacological adjuncts to improve survival after exsanguination CA, and for elucidating the underlying mechanisms of ischemia/reperfusion injury.
authors.affiliation: Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA. drabekt@anes.upmc.edu
authors.forename: Tomas
authors.initials: T
authors.lastname: Drabek
authors.forename: Jason
authors.initials: J
authors.lastname: Stezoski
authors.forename: Robert H
authors.initials: RH
authors.lastname: Garman
authors.forename: Fei
authors.initials: F
authors.lastname: Han
authors.forename: Jeremy
authors.initials: J
authors.lastname: Henchir
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Tisherman
authors.forename: S William
authors.initials: SW
authors.lastname: Stezoski
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
mesh_terms: D000818:Animals; D002315:Cardiopulmonary Bypass; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004334:Drug Administration Schedule; D004573:Electrolytes / Q000008:administration & dosage; D006323:Heart Arrest / Q000150:complications / Q000473:pathology / Q000628:therapy*; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D009422:Nervous System Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D013997:Time Factors
chemical_list: D004573:Electrolytes; C048013:Plasmalyte A