BackgroundSodium ion transportation plays a crucial role in the pathogenesis of hypoxic–ischemic brain injury. Amiodarone, a Vaughan-Williams class III antiarrhythmic drug, has been widely used to treat life-threatening arrhythmia and cardiac arrest worldwide. In addition to its inhibitory effects on the potassium channel, amiodarone also blocks various sodium ion transporters, including the voltage-gated sodium channel, sodium pump, and Na+/Ca+ exchanger. Considering these pharmacological profile, amiodarone may affect the influx–efflux balance of sodium ion in the hypoxic–ischemic brain. Previous studies suggest that the blockade of the voltage-gated sodium channel during hypoxic–ischemic brain injury exerts neuroprotection. On the contrary, the blockade of sodium pump or Na+/Ca+ exchanger during hypoxia–ischemia may cause further intracellular sodium accumulation and consequent osmotic cell death. From these perspectives, the effects of amiodarone on sodium ion balance on the hypoxic–ischemic brain can be both protective and detrimental depending on the clinical and pathophysiological conditions. In this study, we therefore investigated the effect of amiodarone on hypoxic–ischemic brain injury using a murine experimental model.ResultsCompared with the control group mice, mice that received amiodarone after induction of 40-min hypoxic–ischemic brain injury exhibited lower survival rates over 7 days and worse neurological function. After 25-min hypoxic–ischemic brain injury, amiodarone treated mice exhibited larger infarct volumes (16.0 ± 6.9 vs. 24.2 ± 6.8 mm3, P < 0.05) and worse neurological function. In addition, the brains harvested from the amiodarone-treated mice contained larger amounts of sodium (194.7 ± 45.1 vs. 253.5 ± 50.9 mEq/kg dry weight, P < 0.01) and water (259.3 ± 8.9 vs. 277.2 ± 12.5 mg, P < 0.01). There were no significant differences in hemodynamic parameters between groups.ConclusionsAmiodarone exacerbated brain injuries and neurological outcomes after hypoxic–ischemic insults. Severe brain sodium accumulation and brain edema were associated with the detrimental effects of amiodarone. Amiodarone at the clinical dose can exacerbate brain injury after hypoxic–ischemic insult by affecting sodium ion transportation and facilitate intracellular sodium accumulation in the brain.

中文翻译：

---

胺碘酮加剧小鼠缺氧缺血性损伤后的脑损伤

背景钠离子转运在缺氧缺血性脑损伤的发病机制中起着至关重要的作用。胺碘酮是一种 Vaughan-Williams III 类抗心律失常药物，已在全球广泛用于治疗危及生命的心律失常和心脏骤停。除了对钾通道的抑制作用外，胺碘酮还阻断各种钠离子转运体，包括电压门控钠通道、钠泵和 Na+/Ca+ 交换器。考虑到这些药理学特征，胺碘酮可能会影响缺氧缺血脑中钠离子的流入流出平衡。先前的研究表明，在缺氧缺血性脑损伤期间，电压门控钠通道的阻断发挥了神经保护作用。相反，缺氧缺血期间钠泵或 Na+/Ca+ 交换器的阻断可能导致细胞内钠的进一步积累和随之而来的渗透性细胞死亡。从这些角度来看，胺碘酮对缺氧缺血脑钠离子平衡的影响可能具有保护性和有害性，具体取决于临床和病理生理条件。因此，在本研究中，我们使用小鼠实验模型研究了胺碘酮对缺氧缺血性脑损伤的影响。 结果与对照组小鼠相比，在诱导 40 分钟缺氧缺血性脑损伤后接受胺碘酮的小鼠的存活率低于对照组小鼠。 7 天及更糟的神经功能。在 25 分钟缺氧缺血性脑损伤后，胺碘酮治疗的小鼠表现出更大的梗死体积（16.0 ± 6.9 与 24.2 ± 6.8 mm3，P < 0。05）和更糟的神经功能。此外，从胺碘酮治疗的小鼠中收获的大脑含有大量的钠（194.7 ± 45.1 与 253.5 ± 50.9 mEq/kg 干重，P < 0.01）和水（259.3 ± 8.9 与 277.2 ± 12.5 mg，P < 0.01)。各组之间的血流动力学参数没有显着差异。结论胺碘酮会加剧缺氧缺血性损伤后的脑损伤和神经系统结果。严重的脑钠积累和脑水肿与胺碘酮的有害作用有关。临床剂量的胺碘酮可通过影响钠离子转运和促进脑内细胞内钠的积累，加剧缺氧缺血性损伤后的脑损伤。从胺碘酮治疗的小鼠中收获的大脑含有大量的钠（194.7 ± 45.1 与 253.5 ± 50.9 mEq/kg 干重，P < 0.01）和水（259.3 ± 8.9 与 277.2 ± 12.5 mg，P < 0.01） . 各组之间的血流动力学参数没有显着差异。结论胺碘酮会加剧缺氧缺血性损伤后的脑损伤和神经系统结果。严重的脑钠积累和脑水肿与胺碘酮的有害作用有关。临床剂量的胺碘酮可通过影响钠离子转运和促进脑内细胞内钠的积累，加剧缺氧缺血性损伤后的脑损伤。从胺碘酮治疗的小鼠中收获的大脑含有大量的钠（194.7 ± 45.1 与 253.5 ± 50.9 mEq/kg 干重，P < 0.01）和水（259.3 ± 8.9 与 277.2 ± 12.5 mg，P < 0.01） . 各组之间的血流动力学参数没有显着差异。结论胺碘酮会加剧缺氧缺血性损伤后的脑损伤和神经系统结果。严重的脑钠积累和脑水肿与胺碘酮的有害作用有关。临床剂量的胺碘酮可通过影响钠离子转运并促进脑内细胞内钠的积累，从而加剧缺氧缺血性损伤后的脑损伤。各组之间的血流动力学参数没有显着差异。结论胺碘酮会加剧缺氧缺血性损伤后的脑损伤和神经系统结果。严重的脑钠积累和脑水肿与胺碘酮的有害作用有关。临床剂量的胺碘酮可通过影响钠离子转运和促进脑内细胞内钠的积累，加剧缺氧缺血性损伤后的脑损伤。各组之间的血流动力学参数没有显着差异。结论胺碘酮会加剧缺氧缺血性损伤后的脑损伤和神经系统结果。严重的脑钠积累和脑水肿与胺碘酮的有害作用有关。临床剂量的胺碘酮可通过影响钠离子转运和促进脑内细胞内钠的积累，加剧缺氧缺血性损伤后的脑损伤。