Ferimer H N, Kutina K L, LaManna J C
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4938, USA.
Crit Care Med. 1995 Jun;23(6):1106-11. doi: 10.1097/00003246-199506000-00017.
The sodium/hydrogen ion (Na+/H+) antiporter system of brain cells is responsible for reducing intracellular acid loads and regulating cellular volume. Activation of this system during reperfusion following cardiac arrest may contribute to cerebral edema and subsequent brain damage. Therefore, we wished to determine whether administration of methyl isobutyl amiloride, a known inhibitor of the Na+/H+ antiporter system, would cross the blood brain barrier and delay the return of brain intracellular pH to normal values during reperfusion after cardiac arrest in rats.
a) Prospective sequential evaluation of the regional brain blood flow and 3H-methyl isobutyl amiloride extraction fraction in rats; b) prospective sequential evaluation of brain intracellular pH in rats treated with methyl isobutyl amiloride compared with untreated control rats.
A research laboratory.
Thirteen male Wistar rats: a) three rats to study regional brain blood flow and 3H-methyl isobutyl amiloride cerebral extraction; and b) ten rats to study the effect of methyl isobutyl amiloride on brain intracellular pH after cardiac arrest and reperfusion.
a) Rats were injected with 14C iodoantipyrine and 3H-methyl isobutyl amiloride, and their brains were subsequently analyzed to determine regional cerebral blood flow and percent of cerebral extraction of methyl isobutyl amiloride. b) Cardiac arrest was induced with potassium chloride followed by resuscitation 7 mins later in untreated control rats and rats treated with methyl isobutyl amiloride.
a) Regional cerebral blood flow (mL/100 g/min) determined with 14C iodoantipyrine and percent of cerebral extraction of 3H-methyl isobutyl amiloride were evaluated in various regions of the brain. Mean +/- SD values were 167 +/- 15 and 7 +/- 1 for the frontal cerebral cortex; 159 +/- 10 and 7 +/- 2 for the parietal cerebral cortex, 130 +/- 17 and 8 +/- 1 for the hippocampus, 154 +/- 33 and 13 +/- 4 for the cerebellum and 166 +/- 27 and 6 +/- 1 for the striatum (mL/100 g/min). These values were determined by a dual label indicator fractionation method. b) Brain intracellular pH was measured by neutral red histophotometry after 15 mins of reperfusion following cardiac arrest. As compared with untreated control rats, methyl isobutyl amiloride-treated animals had significantly lower brain intracellular pH values after 15 mins of reperfusion. Mean +/- SD pH values were 6.78 +/- 0.18 for the rats treated with methyl isobutyl amiloride vs. normal intracellular pH of 7.11 +/- 0.07 for the untreated control rats.
a) Methyl isobutyl amiloride crosses the blood brain barrier of rats. b) The Na+/H+ antiporter system is operative during reperfusion after cardiac arrest in rats.
脑细胞的钠/氢离子（Na+/H+）逆向转运体系统负责减少细胞内酸负荷并调节细胞体积。心脏骤停后再灌注期间该系统的激活可能导致脑水肿及随后的脑损伤。因此，我们希望确定给予甲基异丁基阿米洛利（一种已知的Na+/H+逆向转运体系统抑制剂）是否会穿过血脑屏障，并在大鼠心脏骤停后的再灌注期间延迟脑内细胞内pH值恢复到正常水平。
a）对大鼠脑局部血流和3H-甲基异丁基阿米洛利提取率进行前瞻性序贯评估；b）对用甲基异丁基阿米洛利治疗的大鼠与未治疗的对照大鼠的脑细胞内pH值进行前瞻性序贯评估。
一个研究实验室。
13只雄性Wistar大鼠：a）3只大鼠用于研究脑局部血流和3H-甲基异丁基阿米洛利的脑提取情况；b）10只大鼠用于研究甲基异丁基阿米洛利对心脏骤停和再灌注后脑细胞内pH值的影响。
a）给大鼠注射14C碘安替比林和3H-甲基异丁基阿米洛利，随后分析它们的大脑以确定脑局部血流和甲基异丁基阿米洛利的脑提取百分比。b）在未治疗的对照大鼠和用甲基异丁基阿米洛利治疗的大鼠中，用氯化钾诱导心脏骤停，7分钟后进行复苏。
a）用14C碘安替比林测定脑局部血流（mL/100 g/分钟），并评估3H-甲基异丁基阿米洛利在大脑各区域的提取百分比。额叶皮质的平均值±标准差分别为167±15和7±1；顶叶皮质为159±10和7±2，海马体为130±17和8±1，小脑为154±33和13±4，纹状体为166±27和6±1（mL/100 g/分钟）。这些值通过双标记指示剂分级法测定。b）心脏骤停后再灌注15分钟后，用中性红组织光度法测量脑细胞内pH值。与未治疗的对照大鼠相比，用甲基异丁基阿米洛利治疗的动物在再灌注15分钟后脑细胞内pH值明显较低。用甲基异丁基阿米洛利治疗的大鼠的平均±标准差pH值为6.78±0.18，而未治疗的对照大鼠的细胞内正常pH值为7.11±0.07。
a）甲基异丁基阿米洛利可穿过大鼠的血脑屏障。b）Na+/H+逆向转运体系统在大鼠心脏骤停后的再灌注期间起作用。
