実験的脳虚血に対するCa^<++>拮抗剤とbarbiturateの脳保護作用について
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概要
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Calcium-antagonist (nicardipine, 0.1 mg/kg), barbiturate (thiamylal, 100 mg/kg), and saline as control were intraperitoneally administered to mongolian gerbils prior to the 20 minutes of ischemia, produced by bilateral clipping of the common carotid arteries of the animals. (1) The survival rates at either 24 hours or 14 days of recirculation of the animals, pretreated with nicardipine (n=30) and thiamylal (n=44), respectively, were significantly higher than that of control (n=64) (p<0.05). (2) The changes in cerebral concentrations of adenosine triphosphate (ATP), phosphocreatine (P-Cr), glucose, lactate, and cyclic-adenosine 3'5'-monophosphate (C-AMP) were assayed during ischemia, and at various periods of recirculation after ischemia. During ischemia, accumulation of lactate and decreased concentration of the energy metabolites were similarly found in control and experimental animals with premedication. As early as 5 minutes after beginning recirculation, however, ATP and P-Cr increased up to 75% and 98% of control values, respectively, in the animals treated by nicardipine, whereas recovery of the controls and thiamylal-treated animals was not significant. At 30 minutes of recirculation in the control animals, the energy metabolites were restored as high as the control level, but two fold or more reaccumulation of lactate and significant decrease in ATP concentration occurred at 360 minutes of recirculation. In both groups of experimental animals with premedication, however, there were neither accumulation of lactate nor decrease of ATP concentration at 360 minutes. At the same time, the high energy phosphate utilization rate in both experimental groups measured in various periods of recirculation was found to be decreased compared to that of control groups. (3) Overshoot of C-AMP at 5 minutes of recirculation was found in all animals treated with or without premedication but the rate of the overshoot in thiamylal-treated animals was significantly lower than those of others. It seems that both calcium-antagonist and barbiturate similarly demonstrate protective effects possibly by decreasing the energy demand of the brain during ischemia-recirculation periods. When compared with the effects of barbiturate during early periods of recirculation, calcium-antagonist appears to facilitate the rapid recovery of ATP and P-Cr regeneration, which are the indicators of mitochondrial activities. The physiological significance of relevant changes in C-AMP overshoot during early periods of recirculation, however, is not clearly understood.
- 社団法人 日本脳神経外科学会の論文
- 1987-05-15