Yanamoto H, Nagata I, Nakahara I, Tohnai N, Zhang Z, Kikuchi H
Laboratory for Cerebrovascular Disorders, National Cardio-Vascular Center Research Institute, Osaka, Japan.
Stroke. 1999 Dec;30(12):2720-6; discussion 2726. doi: 10.1161/01.str.30.12.2720.
It is not known whether a combination of intraischemic and postischemic mild hypothermia provides extra neuroprotection and if so, whether the neuroprotection is persistent.
Sixty-eight Sprague-Dawley rats were used. In group 1, ischemia and reperfusion were performed under normothermic (N) conditions (control, N-N). In group 2, ischemia was induced and maintained under hypothermic conditions (33 degrees C for 2 hours) and reperfusion was performed under normothermic conditions, H-N. In group 3, both ischemia and reperfusion were performed under hypothermic conditions for an additional 21 hours after the surgery, H-22H. In group 4, ischemia was induced and maintained under hypothermic conditions and reperfusion was performed under hypothermic conditions only for the initial 3 hours (H-3H). In group 5, ischemia was induced and maintained under normothermic conditions and reperfusion was performed under hypothermic conditions (33 degrees C) (N-22H). All rats were perfused 48 hours after the induction of ischemia. In addition, the normothermic or hypothermic therapy used for groups 1, 3, and 4 was performed again, and these rats were killed 30 days after the induction of ischemia. Furthermore, neurological deficits were monitored in groups N-N and H-22H for 4 weeks.
In the H-3H and H-22H groups, the total infarct volume was significantly reduced by 41% or 66%, respectively, assessed 48 hours after ischemia. The significant reduction in group H-22H was again confirmed 30 days after ischemia, ie, 50% reduction was observed. In contrast, the reduction in group H-3H (31%) was not significant. The neurological deficits were significantly more severe in the N-N group than in the H-22H group during week 4.
The neuroprotective effects against temporary focal ischemia evaluated by infarct volume and neurological functions by the combination therapy with intraischemic and prolonged postischemic mild hypothermia were persistent in rats. Appropriate design of mild hypothermia therapy extending into the late reperfusion period is important to maximize the neuroprotective effects of hypothermia.
目前尚不清楚缺血期和缺血后轻度低温联合应用是否能提供额外的神经保护作用，若能提供，这种神经保护作用是否持久。
使用68只Sprague-Dawley大鼠。第1组在常温（N）条件下进行缺血和再灌注（对照组，N-N）。第2组在低温条件下（33℃，持续2小时）诱导并维持缺血，然后在常温条件下进行再灌注，即H-N。第3组在手术后，缺血和再灌注均在低温条件下额外持续21小时，即H-22H。第4组在低温条件下诱导并维持缺血，仅在最初3小时在低温条件下进行再灌注，即H-3H。第5组在常温条件下诱导并维持缺血，然后在低温条件下（33℃）进行再灌注，即N-22H。所有大鼠在缺血诱导后48小时进行灌注。此外，对第1、3和4组所用的常温或低温治疗再次进行，这些大鼠在缺血诱导后30天处死。此外，对N-N组和H-22组的神经功能缺损进行了4周的监测。
在缺血后48小时评估，H-3H组和H-22H组的总梗死体积分别显著减少了41%或66%。缺血后30天再次证实H-22H组有显著减少，即观察到减少了50%。相比之下，H-3H组减少31%并不显著。在第4周时，N-N组的神经功能缺损明显比H-22H组严重。
通过梗死体积和神经功能评估，缺血期和延长的缺血后轻度低温联合治疗对大鼠短暂性局灶性缺血的神经保护作用是持久的。适当设计延伸至再灌注后期的轻度低温治疗对于最大限度发挥低温的神经保护作用很重要。
