Circulation of red blood cells having high levels of 2,3-bisphosphoglycerate protects rat brain from ischemic metabolic changes during hemodilution.
Circulation of red blood cells having high levels of 2,3-bisphosphoglycerate protects rat brain from ischemic metabolic changes during hemodilution.
复制标题
含有高水平 2,3-二磷酸甘油酸的红细胞循环可保护大鼠大脑在血液稀释过程中免受缺血性代谢变化的影响。
作者：
H. Kimura;N. Hamasaki;M. Yamamoto;M. Tomonaga
背景和目的
我们设计了本研究，以检查红细胞供氧能力对缺血性脑代谢的影响，在血液稀释过程中，红细胞2，3-二磷酸甘油酸含量。
方法
红细胞2，3-二磷酸甘油酸含量的修改是通过血液交换输血，其中红细胞用磷酸（烯醇）丙酮酸盐或无机磷酸盐在自发性高血压大鼠。输血期间循环血液的红细胞压积值在30%至20%之间变化。采用双侧颈总动脉夹闭60分钟造成大鼠脑缺血模型。通过酶法估计血液中ATP和2，3-二磷酸甘油酸的浓度以及脑中ATP、磷酸肌酸和乳酸的浓度。
结果
输注后，红细胞2，3-二磷酸甘油酸浓度增加至输注前水平的200%，其中红细胞用磷酸（烯醇）丙酮酸盐处理，而输注后，红细胞用磷酸盐处理，浓度降低至80%。输血后磷酸（烯醇）丙酮酸盐和磷酸盐处理组之间红细胞ATP含量没有显着差异。当红细胞压积约为30%时，缺血脑ATP和乳酸含量在非缺血组和缺血组之间没有差异。然而，当血细胞比容降低到低于25%时，在2，3-二磷酸甘油酸-亚正常红细胞组中，缺血性脑ATP含量显著降低，乳酸含量显著增加。与此相反，在2，3-二磷酸甘油酸丰富的红细胞组的缺血脑ATP和磷酸肌酸含量被保存，并在相同的条件下，在非缺血组的那些一样高。
结论
由于血细胞比容降低到最佳水平，脑缺血得到脑血流量增加的补偿，但极度血液稀释导致脑组织供氧不足，导致脑代谢更明显的损害，尽管脑血流量增加。然而，即使在极端的血液稀释条件下，循环血液中富含2，3-二磷酸甘油酸的红细胞也能保护大脑免受缺血性代谢变化的影响。这些结果表明，循环血液中富含2，3-二磷酸甘油酸的红细胞因此可以通过在缺血性损伤时提供充足的氧气供应来补偿极度贫血条件下氧气供应不足。
BACKGROUND AND PURPOSE
We designed the present study to examine the effects of red blood cell oxygen-delivering capacity on ischemic brain metabolism during hemodilution with respect to red blood cell 2,3-bisphosphoglycerate content.
METHODS
A modification of red blood cell 2,3-bisphosphoglycerate content was achieved by an exchange transfusion of blood in which red blood cells were treated with either phospho(enol)pyruvate or inorganic phosphate in spontaneously hypertensive rats. Hematocrit values of circulating blood were varied from 30% to 20% during transfusion. Brain ischemia was produced in rats by bilateral carotid artery occlusion lasting 60 minutes. The concentrations of ATP and 2,3-bisphosphoglycerate in the blood and the ATP, phosphocreatine, and lactate concentrations in the brain were estimated by an enzymatic method.
RESULTS
Red blood cell 2,3-bisphosphoglycerate concentration increased to 200% of the pretransfusion level after the transfusion in which red blood cells were treated with phospho(enol)pyruvate, whereas the concentration decreased to 80% after the transfusion in which red blood cells were treated with phosphate. Red blood cell ATP content did not differ significantly between the phospho(enol)pyruvate- and phosphate-treated groups after transfusion. When hematocrit was approximately 30%, the ischemic brain ATP and lactate contents did not differ between the nonischemic and ischemic groups. However, as hematocrit was reduced to less than 25% the ischemic brain ATP content remarkably decreased and the lactate content substantially increased in the 2,3-bisphosphoglycerate-subnormal red blood cell group. In contrast, the ischemic brain ATP and phosphocreatine contents in the 2,3-bisphosphoglycerate-enriched red blood cell group were preserved and as high as those in the nonischemic group under the same conditions.
CONCLUSIONS
Cerebral ischemia was compensated with the increment of cerebral blood flow as a result of the reduction of hematocrit to optimal levels, but the extreme hemodilution induced insufficient oxygen supply to the brain tissue, resulting in a more marked impairment of brain metabolism despite an increase in cerebral blood flow. However, even in extreme hemodilution conditions the 2,3-bisphosphoglycerate-enriched red blood cells in circulating blood protected the brain from ischemic metabolic changes. These results suggest that the 2,3-bisphosphoglycerate-enriched red blood cells in the circulating blood may thus compensate for the insufficient oxygen supply in extremely anemic conditions by providing a sufficient supply of oxygen in the face of ischemic insult.