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喹吡罗和 8-OH-DPAT 促进心脏骤停大鼠模型的体温降低。

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

机构信息

Department of Anaesthesiology and Intensive Care Medicine, University of Cologne, Kerpener Straße 62, 50937 Köln, Germany. andreas.schneider @uk-koeln.de

出版信息

Resuscitation. 2012 Feb;83(2):232-7. doi: 10.1016/j.resuscitation.2011.07.023. Epub 2011 Jul 29.

DOI:10.1016/j.resuscitation.2011.07.023
PMID:21803015
Abstract

AIM OF THE STUDY

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.

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.

摘要

研究目的

心脏骤停后,治疗性低温可改善预后。多巴胺 D2 激动剂和 5-羟色胺 5-HT1A 激动剂通过降低设定点来降低体温。我们研究了这些药物对心脏骤停后大鼠体温和大脑恢复的影响。

方法

雄性 Wistar-Han 大鼠因心室颤动而发生 6 分钟的心脏骤停。循环恢复后,皮下注射 1mg 喹吡罗、1mg 8-OH-DPAT 或载体。监测体温 48 小时。另外一组保持正常体温。通过胶带去除试验对动物进行神经学测试。7 天后,用尼氏染色和 TUNEL 染色分析海马 CA-1 区的组织学。

结果

大鼠心脏骤停后自发出现体温过低。与载体(-0.020 ± 0.005°C/min)相比,喹吡罗(-0.033 ± 0.008°C/min)和 8-OH-DPAT(-0.029 ± 0.010°C/min)诱导体温过低更容易。低温的总“剂量”(曲线下面积)没有差异。所有动物均出现神经功能缺损,随着时间的推移而改善;7 天后,正常体温组(30 [11-88]s)的测试结果仍倾向于比低温组(载体 8 [6-14]s,喹吡罗 9 [4-17]s,8-OH-DPAT 10 [8-22]s)差。7 天后尼氏染色或 TUNEL 组织学无明显差异。

结论

喹吡罗和 8-OH-DPAT 均导致体温更快下降。然而,结果与自发性低温无差异,可能是因为低温的总“剂量”没有受到影响。

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