Impact of therapeutic hypothermia onset and duration on survival, neurologic function, and neurodegeneration after cardiac arrest.

Impact of therapeutic hypothermia onset and duration on survival, neurologic function, and neurodegeneration after cardiac arrest.
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DOI:
10.1097/ccm.0b013e318212020a
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发表时间:
2011-06
影响因子:
8.8
通讯作者:
Neumar RW
Neumar RW
中科院分区:
医学1区
文献类型:
--
作者:
Che D;Li L;Kopil CM;Liu Z;Guo W;Neumar RW

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心脏骤停后治疗性低温(TH)可改善昏迷的心脏骤停幸存者的预后。这项研究验证了心脏骤停后TH的疗效取决于治疗的开始和持续时间的假设。前瞻性随机实验室调查大学研究实验室268只雄性Long Evans大鼠心脏骤停治疗性低温后,成年雄性Long Evans大鼠在窒息心脏骤停10分钟后恢复自主循环(ROSC),随机分成常温(37±1℃)或TH(33±1℃)组,在ROSC后0、1、4或8小时开始,并维持24或48小时。在ROSC后0、1、4和8小时开始TH,7天存活率分别为45%*、36%*、36%*和14%,而常温对照组为17%;神经功能良好的存活率分别为24%*、24%*、19%*和0%,而常温对照组为2%(P<0.05对常温对照组)。当TH维持24小时与48小时时,这些结果没有差别。相反,在ROSC后0、1、4或8小时,海马区CA1区锥体神经元计数分别为正常的53±27%、53±19%、51±24%和65±16%,而常温对照组为9%(P<0.01 vs常温)。此外,与24小时相比,维持TH 48小时的存活神经元数量更多(68%±15%*vs.42%±22%,p<0.0001)。在本研究中,心脏骤停后TH的存活率和存活率均有类似的改善,且神经功能良好。然而,神经元存活的组织学评估显示,当TH维持48小时而不是24小时时,潜在的治疗窗口更宽,神经保护更强。
Post-cardiac arrest therapeutic hypothermia (TH) improves outcomes in comatose cardiac arrest survivors. This study tests the hypothesis that the efficacy of post-cardiac arrest TH is dependent on the onset and duration of therapy. Prospective randomized laboratory investigation University research laboratory 268 male Long Evans rats Post-cardiac arrest therapeutic hypothermia Adult male Long Evans rats that achieved return of spontaneous circulation (ROSC) after a 10-min asphyxial cardiac arrest were block randomized to normothermia (37±1°C) or TH (33±1°C) initiated 0, 1, 4, or 8 hrs after ROSC and maintained for 24 or 48 hrs. TH initiated 0, 1, 4, and 8 hours after ROSC resulted in 7-day survival rates of 45%*, 36%*, 36%*, and 14% respectively compared to 17% for normothermic controls, and survival with good neurologic function rates of 24%*, 24%*, 19%*, and 0% respectively compared to 2% for normothermic controls (*p<0.05 vs. normothermia). These outcomes were not different when TH was maintained for 24 vs. 48 hours. In contrast, hippocampal CA1 pyramidal neuron counts were 53±27%*, 53±19%*, 51±24%*, and 65±16%* of normal respectively when TH initiated 0, 1, 4, or 8 hrs after ROSC compared to 9% in normothermic controls (*p<0.01 vs. normothermia). Furthermore, surviving neuron counts were greater when TH was maintained for 48 hrs compared to 24 hrs (68%±15%* vs. 42%±22%, *p<0.0001) In this study, post-cardiac arrest TH resulted in comparable improvement of survival and survival with good neurologic function when initiated within 4-hours after ROSC. However, histological assessment of neuronal survival revealed a potentially broader therapeutic window and greater neuroprotection when TH was maintained for 48 vs. 24 hours.