title: Facilitation of hypothermia by quinpirole and 8-OH-DPAT in a rat model of cardiac arrest.
abstract: OBJECTIVE
  Therapeutic hypothermia improves outcome after cardiac arrest. Dopamine D(2) agonists and serotonin 5-HT(1A) agonists lower body temperature by decreasing the set-point. We investigated the effect of these drugs on temperature and cerebral recovery of rats after cardiac arrest.
  
  
  METHODS
  Male Wistar-Han rats were subjected to 6 min of cardiac arrest due to ventricular fibrillation. Following restoration of circulation, 1mg quinpirole, 1mg 8-OH-DPAT or vehicle were injected subcutaneously. Body temperature was monitored for 48 h. One additional group was kept normothermic. Animals were neurologically tested by a tape removal test. After 7 days, histology of hippocampal CA-1 sector was analysed with Nissl and TUNEL staining.
  
  
  RESULTS
  Rats became spontaneously hypothermic after cardiac arrest. Induction of hypothermia was facilitated by both quinpirole (-0.033 ± 0.008°C/min) and 8-OH-DPAT (-0.029 ± 0.010°C/min) when compared to vehicle (-0.020 ± 0.005°C/min). Total 'dose' of hypothermia (area under the curve) was not different. All animals showed a neurological deficit, which improved with time; after 7 days, test results of the normothermic group (30 [11-88]s) still tended to be worse than those of the hypothermic groups (vehicle 8 [6-14]s, quinpirole 9 [4-17]s, 8-OH-DPAT 10 [8-22]s). There were no clear differences in Nissl or TUNEL histology after 7 days.
  
  
  CONCLUSIONS
  Both quinpirole and 8-OH-DPAT led to faster induction of hypothermia. However, the outcome was not different from spontaneous hypothermia, probably because the total 'dose' of hypothermia was not influenced.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University of Cologne, Kerpener Straße 62, 50937 Köln, Germany. andreas.schneider @uk-koeln.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneider
authors.forename: Peter
authors.initials: P
authors.lastname: Teschendorf
authors.forename: Peter
authors.initials: P
authors.lastname: Vogel
authors.forename: Nicolai
authors.initials: N
authors.lastname: Russ
authors.forename: Jürgen
authors.initials: J
authors.lastname: Knapp
authors.forename: Bernd W
authors.initials: BW
authors.lastname: Böttiger
authors.forename: Erik
authors.initials: E
authors.lastname: Popp
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D006323:Heart Arrest / Q000209:etiology / Q000628:therapy*; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D016896:Treatment Outcome; D014693:Ventricular Fibrillation / Q000150:complications
chemical_list: D018491:Dopamine Agonists; D017366:Serotonin Receptor Agonists; D019257:Quinpirole; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin