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

Abstract 

Aim of the study

Therapeutic hypothermia improves outcome after cardiac arrest. Dopamine D₂ 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 6min 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 48h. 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.

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.

Keywords: Cardiac arrest, Hypothermia, Neurological dysfunction