The effect of nimodipine on high-energy phosphates and intracellular pH during cerebral ischemia.
The effect of nimodipine on high-energy phosphates and intracellular pH during cerebral ischemia.
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尼莫地平对脑缺血时高能磷酸盐和细胞内pH的影响。
DOI：
10.1089/neu.1993.10.73
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发表时间：
1993
影响因子：
4.2
通讯作者：
WagnerJr,FC
中科院分区：
文献类型：
--
作者：
Lemons,V;Chehrazi,BB;Kauten,R;Hein,L;WagnerJr,FC
实验和临床研究表明，钙通道阻滞剂尼莫地平可减轻脑缺血损伤。利用快速采集磷-31核磁共振（31 P NMR）光谱，我们研究了尼莫地平对沙土鼠严重缺血时脑能量代谢的影响。高能磷酸盐和细胞内pH值的特点是在基线和2分钟的时间间隔后，双侧颈总动脉（CCA）结扎。连续前脑波谱分析持续进行，直到磷酸肌酸（PCr）和三磷酸腺苷（ATP）共振消失。将对照组（n= 10）与在颈动脉结扎前30分钟接受以下剂量的腹膜内尼莫地平的沙鼠进行比较：0.5 mg/kg（n= 8）、1.0 mg/kg（n= 10）、2.0 mg/kg（n= 8）或4.0 mg/kg（n= 4）。在对照组中，CCA结扎后平均5.4 ± 0.47min，PCr和ATP峰检测不到。与对照组相比，尼莫地平0.5 mg/kg和1.0 mg/kg剂量组颈动脉结扎后高能磷酸盐消耗的平均时间延长，但差异无统计学意义。然而，在2.0 mg/kg组中，ATP保留至缺血发作后9.8 ± 1.0 min，显著长于对照组（p= 0.005，Mann-Whitney检验）。尼莫地平对细胞内酸中毒的时间进程或严重程度没有影响。在这个严重缺血的模型中，相对高剂量的尼莫地平减缓了高能磷酸盐的消耗，而不改变细胞内酸中毒。这表明尼莫地平可能通过直接改变缺血细胞代谢来提供脑保护。
Experimental and clinical studies suggest that the calcium channel blocker nimodipine may reduce cerebral ischemic injury. Using rapid acquisition phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy, we examined the effect of nimodipine on cerebral energy metabolism during severe ischemia in gerbils. High-energy phosphates and intracellular pH were characterized at baseline and at 2-min intervals following bilateral common carotid artery (CCA) ligation. Serial forebrain spectroscopy was continued until phosphocreatine (PCr) and adenosine triphosphate (ATP) resonances disappeared. Controls (n= 10) were compared to gerbils receiving intraperitoneal nimodipine 30 min prior to carotid ligation, at the following doses: 0.5 mg/kg (n= 8), 1.0 mg/kg (n= 10), 2.0 mg/kg (n= 8), or 4.0 mg/kg (n= 4).In the control group, PCr and ATP peaks were undetectable after a mean of 5.4 ± 0.47 min following CCA ligation. Compared with controls, the mean time for depletion of high-energy phosphates following carotid ligation was prolonged at nimodipine doses of 0.5 mg/kg and 1.0 mg/kg, but the differences did not reach statistical significance. In the 2.0 mg/kg group, however, ATP was preserved until 9.8 ± 1.0 min following the onset of ischemia, significantly longer than the control group (p= 0.005, Mann-Whitney test). Nimodipine had no effect on the time course or severity of intracellular acidosis. In this model of severe ischemia, relatively high doses of nimodipine slowed the depletion of high-energy phosphates without altering intracellular acidosis. This suggests that nimodipine may provide cerebral protection by directly altering ischemic cellular metabolism.