Toung T J, Kirsch J R, Traystman R J
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
Crit Care Med. 1996 Jan;24(1):103-8. doi: 10.1097/00003246-199601000-00018.
To test the hypothesis that adenosine 3',5'-cyclic monophosphate (cAMP) or dibutyl-cAMP (a more lipid-soluble, less rapidly metabolized analog of cAMP) would improve recovery of cerebral electrical activity and metabolic function after transient global cerebral ischemia by improving cerebral blood flow during the reperfusion period.
Randomized, controlled, prospective study.
University research laboratory.
Twenty-five male beagle dogs.
Nine control dogs received saline (20-mL/kg bolus and 0.01 mL/kg/min) intravenously, beginning 25 mins before 12 mins of cerebral global ischemia (by aortic occlusion). The dogs in the experimental groups received either cAMP (40 mg/kg 25 mins before ischemia and 0.2 mg/kg/min throughout reperfusion, n = 7), or dibutyl-cAMP (6 mg/kg 25 mins before ischemia and 3 mg/kg at 60, 90, and 120 mins of reperfusion, n = 9).
Total and regional cerebral blood flow, cerebral oxygen consumption, and somatosensory evoked potentials were measured during 180 mins of reperfusion. Pretreatment with dibutyl-cAMP resulted in increased postischemic hyperemia at 30 mins of reperfusion (e.g., whole brain: control 40 +/- 6; cAMP 56 +/- 9; dibutyl-cAMP 67 +/- 10 mL/min/100 g [mean +/- SEM, p < .05 control vs. dibutyl-cAMP group]) but no difference in total cerebral blood flow or oxygen consumption during later points of reperfusion. All groups demonstrated rapid ablation of the amplitude of somatosensory evoked potentials during ischemia, with no difference between the groups. At 180 mins of reperfusion, somatosensory evoked potentials recovered to 28 +/- 4% of the preischemic baseline value in dogs treated with saline, whereas the somatosensory evoked potentials recovered to 58 +/- 4% of preischemic baseline value in the cAMP-pretreated group (p < .05), and to 70 +/- 6% of preischemic baseline value in dogs treated with dibutyl-cAMP (p < .05).
cAMP and dibutyl-cAMP improve recovery of cerebral electrical function after complete transient global cerebral ischemia. Although hyperemia was more prolonged in cAMP- and dibutyl-cAMP-treated dogs, there was no difference between groups in degree of postischemic delayed hypoperfusion. Therefore, we believe that the mechanism for cerebral protection afforded by cAMP and dibutyl-cAMP is not related to cerebral circulatory effects.
检验如下假设，即3',5'-环磷酸腺苷（cAMP）或二丁酰 - cAMP（一种脂溶性更高、代谢更慢的cAMP类似物）可通过改善再灌注期脑血流量，促进短暂性全脑缺血后脑电活动及代谢功能的恢复。
随机、对照、前瞻性研究。
大学研究实验室。
25只雄性比格犬。
9只对照犬在全脑缺血12分钟（通过主动脉阻断）前25分钟开始静脉输注生理盐水（20毫升/千克推注量，0.01毫升/千克/分钟）。实验组的犬分别接受cAMP（缺血前25分钟给予40毫克/千克，再灌注全程给予0.2毫克/千克/分钟，n = 7）或二丁酰 - cAMP（缺血前25分钟给予6毫克/千克，再灌注60、90和120分钟时分别给予3毫克/千克，n = 9）。
在180分钟的再灌注期内测量全脑及局部脑血流量、脑氧耗量和体感诱发电位。二丁酰 - cAMP预处理使再灌注30分钟时缺血后充血增加（例如，全脑：对照组40±6；cAMP组56±9；二丁酰 - cAMP组67±10毫升/分钟/100克[均值±标准误，对照组与二丁酰 - cAMP组比较，p < 0.05]），但在再灌注后期全脑血流量或氧耗量无差异。所有组在缺血期间体感诱发电位波幅均迅速消失，组间无差异。再灌注180分钟时，生理盐水处理组犬的体感诱发电位恢复至缺血前基线值的28±4%，而cAMP预处理组恢复至缺血前基线值 的58±4%（p < 0.05），二丁酰 - cAMP处理组犬恢复至缺血前基线值的70±6%（p < 0.05）。
cAMP和二丁酰 - cAMP可促进完全性短暂性全脑缺血后脑电功能的恢复。尽管cAMP和二丁酰 - cAMP处理组犬的充血持续时间更长，但缺血后延迟性灌注不足的程度在组间无差异。因此，我们认为cAMP和二丁酰 - cAMP提供脑保护的机制与脑循环效应无关。
