Milde L N, Milde J H, Michenfelder J D
J Cereb Blood Flow Metab. 1986 Jun;6(3):332-7. doi: 10.1038/jcbfm.1986.56.
Ten minutes of complete cerebral ischemia was produced in 18 dogs by temporary ligation of the aorta and venae cavae. Dogs were randomly assigned to one of three groups. A bolus dose of 10 micrograms kg-1 nimodipine, a dihydropyridine calcium entry blocker, followed by a constant infusion of 1 microgram kg-1 min-1 was given at 15, 30, or 60 min post ischemia. Cerebral blood flow and metabolism were measured for 2 h postischemia. Delayed treatment with nimodipine ameliorated or reversed the cerebral hypoperfusion that routinely occurs after complete ischemia. In the groups treated at 15 and 30 min, CBF remained above 60 ml min-1 100 g-1. In the group treated at 60 min, there was a progressive decline in CBF to 37 ml min-1 100 g-1. Following treatment with nimodipine, CBF immediately increased and was maintained above 50 ml min-1 100 g-1 for the remainder of the study. Once treatment with nimodipine was begun, CBF was approximately double that of an untreated group. Changes in CBF reflected changes in cerebrovascular resistance. Nimodipine had no effect on cerebral metabolism. Since the postischemic hypoperfusion state is believed to contribute to the ultimate neurologic damage following complete ischemia, treatment with nimodipine, even if delayed up to 60 min, may improve the outcome.
通过暂时结扎主动脉和腔静脉，在18只狗身上造成10分钟的全脑缺血。将狗随机分为三组。在缺血后15、30或60分钟给予一剂10微克/千克的尼莫地平（一种二氢吡啶类钙通道阻滞剂）推注，随后以1微克/千克·分钟的速度持续输注。在缺血后2小时测量脑血流量和代谢。尼莫地平延迟治疗改善或逆转了全脑缺血后通常出现的脑灌注不足。在15分钟和30分钟治疗的组中，脑血流量在100克脑组织每分钟60毫升以上。在60分钟治疗的组中，脑血流量逐渐下降至100克脑组织每分钟37毫升。给予尼莫地平治疗后，脑血流量立即增加，并在研究的剩余时间内维持在100克脑组织每分钟50毫升以上。一旦开始使用尼莫地平治疗，脑血流量约为未治疗组的两倍。脑血流量的变化反映了脑血管阻力的变化。尼莫地平对脑代谢没有影响。由于缺血后灌注不足状态被认为是全脑缺血后最终神经损伤的原因，即使延迟至60分钟进行尼莫地平治疗，也可能改善预后。
