Department of Hepatology, Rigshospitalet, Copenhagen, Denmark.
Hepatology. 2011 Jun;53(6):1986-94. doi: 10.1002/hep.24274.
Intravenous infusion of magnesium sulfate prevents seizures in patients with eclampsia and brain edema after traumatic brain injury. Neuroprotection is achieved by controlling cerebral blood flow (CBF), intracranial pressure, neuronal glutamate release, and aquaporin-4 (Aqp4) expression. These factors are also thought to be involved in the development of brain edema in acute liver failure. We wanted to study whether hypermagnesemia prevented development of intracranial hypertension and hyperperfusion in a rat model of portacaval anastomosis (PCA) and acute hyperammonemia. We also studied whether hypermagnesemia had an influence on brain content of glutamate, glutamine, and aquaporin-4 expression. The study consisted of three experiments: The first was a dose-finding study of four different dosing regimens of magnesium sulfate (MgSO4) in healthy rats. The second involved four groups of PCA rats receiving ammonia infusion/vehicle and MgSO4) /saline. The effect of MgSO(4) on mean arterial pressure (MAP), intracranial pressure (ICP), CBF, cerebral glutamate and glutamine, and aquaporin-4 expression was studied. Finally, the effect of MgSO4 on MAP, ICP, and CBF was studied, using two supplementary dosing regimens. In the second experiment, we found that hypermagnesemia and hyperammonemia were associated with a significantly higher CBF (P < 0.05, two-way analysis of variance [ANOVA]). Hypermagnesemia did not lead to a reduction in ICP and did not affect the brain content of glutamate, glutamine, or Aqp-4 expression. In the third experiment, we achieved higher P-Mg but this did not lead to a significant reduction in ICP or CBF.
Our results demonstrate that hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in rats with PCA and hyperammonemia.
静脉输注硫酸镁可预防子痫和创伤性脑损伤后脑水肿患者的癫痫发作。神经保护通过控制脑血流 (CBF)、颅内压、神经元谷氨酸释放和水通道蛋白-4 (Aqp4) 表达来实现。这些因素也被认为与急性肝衰竭后脑水肿的发展有关。我们想研究高镁血症是否可以预防门腔静脉分流术 (PCA) 和急性高氨血症大鼠模型中颅内高血压和高灌注的发展。我们还研究了高镁血症对脑内谷氨酸、谷氨酰胺和水通道蛋白-4 表达的影响。该研究包括三个实验：第一个是在健康大鼠中进行的四种不同硫酸镁 (MgSO4) 剂量方案的剂量发现研究。第二个实验包括四组接受氨输注/载体和 MgSO4/盐水的 PCA 大鼠。研究了 MgSO4 对平均动脉压 (MAP)、颅内压 (ICP)、CBF、脑内谷氨酸和谷氨酰胺以及水通道蛋白-4 表达的影响。最后，研究了两种补充剂量方案对 MAP、ICP 和 CBF 的影响。在第二个实验中，我们发现高镁血症和高氨血症与 CBF 显著升高有关 (P < 0.05，双向方差分析 [ANOVA])。高镁血症并未导致 ICP 降低，也未影响脑内谷氨酸、谷氨酰胺或 Aqp-4 表达。在第三个实验中，我们实现了更高的 P-Mg，但这并没有导致 ICP 或 CBF 显著降低。
我们的结果表明，高镁血症不能预防 PCA 和高氨血症大鼠的颅内高血压并加重脑高灌注。
