title: Survival without brain damage after clinical death of 60-120 mins in dogs using suspended animation by profound hypothermia.
abstract: OBJECTIVE
  This study explored the limits of good outcome of brain and organism achievable after cardiac arrest (no blood flow) of 60-120 mins, with preservation (suspended animation) induced immediately after the start of exsanguination cardiac arrest.
  
  
  METHODS
  Prospective experimental comparison of three arrest times, without randomization.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Twenty-seven custom-bred hunting dogs (17-25 kg).
  
  
  METHODS
  Dogs were exsanguinated over 5 mins to cardiac arrest no-flow of 60 mins, 90 mins, or 120 mins. At 2 mins of cardiac arrest, the dogs received, via a balloon-tipped catheter, an aortic flush of isotonic saline at 2 degrees C (at a rate of 1 L/min), until tympanic temperature reached 20 degrees C (for 60 mins of cardiac arrest), 15 degrees C (for 60 mins of cardiac arrest), or 10 degrees C (for 60, 90, or 120 mins of cardiac arrest). Resuscitation was by closed-chest cardiopulmonary bypass, postcardiac arrest mild hypothermia (tympanic temperature 34 degrees C) to 12 hrs, controlled ventilation to 20 hrs, and intensive care to 72 hrs.
  
  
  RESULTS
  We assessed overall performance categories (OPC 1, normal; 2, moderate disability; 3, severe disability; 4, coma; 5, death), neurologic deficit scores (NDS 0-10%, normal; 100%, brain death), regional and total brain histologic damage scores at 72 hrs (total HDS >0-40, mild; 40-100, moderate; >100, severe damage), and morphologic damage of extracerebral organs. For 60 mins of cardiac arrest (n = 14), tympanic temperature 20 degrees C (n = 6) was achieved after flush of 3 mins and resulted in two dogs with OPC 1 and four dogs with OPC 2: median NDS, 13% (range 0-27%); and median total HDS, 28 (range, 4-36). Tympanic temperature of 15 degrees C (n = 5) was achieved after flush of 7 mins and resulted in all five dogs with OPC 1, NDS 0% (0-3%), and HDS 8 (0-48). Tympanic temperature 10 degrees C (n = 3) was achieved after flush of 11 mins and resulted in all three dogs with OPC 1, NDS 0%, and HDS 16 (2-18). For 90 mins of cardiac arrest (n = 6), tympanic temperature 10 degrees C was achieved after flush of 15 mins and resulted in all six dogs with OPC 1, NDS 0%, and HDS 8 (0-37). For 120 mins of cardiac arrest (n = 7), three dogs had to be excluded. In the four dogs within protocol, tympanic temperature 10 degrees C was achieved after flush of 15 mins. This resulted in one dog with OPC 1, NDS 0%, and total HDS 14; one with OPC 1, NDS 6%, and total HDS 20; one with OPC 2, NDS 13%, and total HDS 10; and one with OPC 3, NDS 39%, and total HDS 22.
  
  
  CONCLUSIONS
  In a systematic series of studies in dogs, the rapid induction of profound cerebral hypothermia (tympanic temperature 10 degrees C) by aortic flush of cold saline immediately after the start of exsanguination cardiac arrest-which rarely can be resuscitated effectively with current methods-can achieve survival without functional or histologic brain damage, after cardiac arrest no-flow of 60 or 90 mins and possibly 120 mins. The use of additional preservation strategies should be pursued in the 120-min arrest model.
authors.affiliation: Safar Center for Resuscitation Research, Pittsburgh, PA, USA.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Behringer
authors.forename: Peter
authors.initials: P
authors.lastname: Safar
authors.forename: Xianren
authors.initials: X
authors.lastname: Wu
authors.forename: Rainer
authors.initials: R
authors.lastname: Kentner
authors.forename: Ann
authors.initials: A
authors.lastname: Radovsky
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.forename: C Edward
authors.initials: CE
authors.lastname: Dixon
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Tisherman
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001831:Body Temperature; D001926:Brain Death; D002315:Cardiopulmonary Bypass / Q000379:methods; D003128:Coma / Q000209:etiology; D003404:Creatinine / Q000378:metabolism; D003422:Critical Care / Q000379:methods; D004195:Disease Models, Animal; D004285:Dogs; D006323:Heart Arrest / Q000150:complications*; D006470:Hemorrhage / Q000150:complications; D007036:Hypothermia, Induced / Q000379:methods*; D002534:Hypoxia, Brain / Q000145:classification / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D008657:Metabolic Clearance Rate; D011446:Prospective Studies; D011897:Random Allocation; D012121:Respiration, Artificial / Q000379:methods; D012151:Resuscitation / Q000379:methods*; D012720:Severity of Illness Index; D016019:Survival Analysis; D013997:Time Factors; D014432:Tympanic Membrane; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D003404:Creatinine; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D001663:Bilirubin