title: Effects of adenosine monophosphate on induction of therapeutic hypothermia and neuronal damage after cardiopulmonary resuscitation in rats.
abstract: BACKGROUND
  Animal studies and pathophysiological considerations suggest that therapeutic hypothermia after cardiopulmonary resuscitation is the more effective the earlier it is induced. Therefore this study is sought to examine whether pharmacological facilitated hypothermia by administration of 5'-adenosine monophosphate (AMP) is neuroprotective in a rat model of cardiac arrest (CA) and resuscitation.
  
  
  METHODS
  Sixty-one rats were subjected to CA. After 6 min of ventricular fibrillation advanced cardiac life support was started. After successful return of spontaneous circulation (ROSC, n=40), animals were randomized either to placebo group (n=14) or AMP group (800 mg/kg body weight, n=14). Animals were kept at an ambient temperature of 18°C for 12 h after ROSC and core body temperature was measured using a telemetry temperature probe. Neuronal damage was analyzed by counting Nissl-positive (i.e. viable) neurons and TUNEL-positive (i.e. apoptotic) cells in coronal brain sections 7 days after ROSC. Functional status evaluated on days 1, 3 and 7 after ROSC by a tape removal test.
  
  
  RESULTS
  Time until core body temperature dropped to <34.0°C was 31 min [28; 45] in AMP-treated animals and 125 min [90; 180] in the control group (p=0.003). Survival until 7 days after ROSC was comparable in both groups. Also number of Nissl-positive cells (AMP: 1 [1; 7] vs. placebo: 2 [1; 3] per 100 pixel; p=0.66) and TUNEL-positive cells (AMP: 56 [44; 72] vs. placebo: 53 [41; 67] per 100 pixel; p=0.70) did not differ. Neither did AMP affect functional neurological outcome up to 7 days after ROSC. Mean arterial pressure 20 min after ROSC was 49 [45; 55] mmHg in the AMP group in comparison to 91 [83; 95] mmHg in the control group (p<0.001).
  
  
  CONCLUSIONS
  Although application of AMP reduced the time to reach a core body temperature of <34°C neither survival was improved nor neuronal damage attenuated. Reason for this is probably induction of marked hypotension as an adverse reaction to AMP treatment.
authors: Department of Anaesthesiology, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany. Electronic address: juergen.knapp@uni-heidelberg.de.
authors: Jürgen
authors: J
authors: Knapp
authors: Department of Anaesthesiology and Postoperative Intensive Care Medicine, University of Cologne, Kerpener Str. 62, D-50937 Köln, Germany.
authors: Andreas
authors: A
authors: Schneider
authors: Department of Anaesthesiology, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany.
authors: Corinna
authors: C
authors: Nees
authors: Institute of Medical Biometry and Informatics, University of Heidelberg, Im Neuenheimer Feld 305, D-69120 Heidelberg, Germany.
authors: Thomas
authors: T
authors: Bruckner
authors: Department of Anaesthesiology and Postoperative Intensive Care Medicine, University of Cologne, Kerpener Str. 62, D-50937 Köln, Germany.
authors: Bernd W
authors: BW
authors: Böttiger
authors: Department of Anaesthesiology, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany.
authors: Erik
authors: E
authors: Popp
mesh_terms: D000249:Adenosine Monophosphate / Q000627:therapeutic use*; D000818:Animals; D016887:Cardiopulmonary Resuscitation / Q000009:adverse effects*; D006323:Heart Arrest / Q000628:therapy*; D007036:Hypothermia, Induced / Q000009:adverse effects*; D008297:Male; D009474:Neurons / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000249:Adenosine Monophosphate
keywords: Adenosine monophosphate; Cardiac arrest; Cardiopulmonary resuscitation (CPR); Therapeutic hypothermia