Facilitation of hypothermia by quinpirole and 8-OH-DPAT in a rat model of cardiac arrest.

Aim of the study: Therapeutic hypothermia improves outcome after cardiac arrest. Dopamine D-2 agonists and serotonin 5-HT1A 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, 1 mg quinpirole, 1 mg 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 degrees C/min) and 8-OH-DPAT (-0.029 +/- 0.010 degrees C/min) when compared to vehicle (-0.020 +/- 0.005 degrees 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. Conclusion: 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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.