Mutoh Tomoko, Mutoh Tatsushi, Sasaki Kazumasu, Nakamura Kazuhiro, Tatewaki Yasuko, Ishikawa Tatsuya, Taki Yasuyuki
Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Japan; Graduate School of Psychology, Kobe Shoin Women's University, Kobe, Japan.
Department of Nuclear Medicine and Radiology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, Sendai, Japan; Research Institute for Brain and Blood Vessels-AKITA, Akita, Japan.
Neurosci Lett. 2017 Feb 15;640:70-75. doi: 10.1016/j.neulet.2017.01.008. Epub 2017 Jan 6.
Acute cerebral hypoperfusion following subarachnoid hemorrhage (SAH) is highly related to the pathogenesis of delayed cerebral ischemia (DCI), but the therapeutic option is poorly available. This study aimed to clarify the effect of milrinone (MIL) on cerebral blood flow (CBF) and related outcomes after experimental SAH.
Twenty-seven male C57BL/6 mice were assigned to either sham surgery (SAH-sham; n=6), SAH induced by endovascular perforation (control; n=10), or SAH followed by cardiac support with intravenous MIL (n=11) performed 1.5-h after SAH induction. CBF, neurobehavioral function, occurrence of DCI were assessed by MR-continuous arterial spin labeling, daily neurological score testing, and diffusion- and T2-weighted MR images on days 1 and 3, respectively.
Initial global CBF depression was notable in mice of control and MIL groups as compared to the SAH-sham group (P<0.05). MIL raised CBF in a dose-dependent manner (P<0.001), resulted in lower incidence of DCI (P=0.008) and better recovery from neurobehavioral decline than control (P<0.001). The CBF values on day 1 predicted DCI with a cut-off of 42.5ml/100g/min (82% specificity and 83% sensitivity), which was greater in mice treated with MIL than those of control (51.7 versus 37.6ml/100g/min; P<0.001).
MIL improves post-SAH acute hypoperfusion that can lead to the prevention of DCI and functional worsening, acting as a neurocardiac protective agent against EBI.
蛛网膜下腔出血（SAH）后的急性脑灌注不足与迟发性脑缺血（DCI）的发病机制高度相关，但治疗选择有限。本研究旨在阐明米力农（MIL）对实验性SAH后脑血流量（CBF）及相关结局的影响。
将27只雄性C57BL/6小鼠分为假手术组（SAH-假手术组；n = 6）、血管内穿刺诱导SAH组（对照组；n = 10）或SAH后1.5小时静脉给予MIL进行心脏支持组（n = 11）。分别在第1天和第3天通过磁共振连续动脉自旋标记、每日神经功能评分测试以及扩散加权和T2加权磁共振成像评估CBF、神经行为功能和DCI的发生情况。
与SAH-假手术组相比，对照组和MIL组小鼠最初的全脑CBF降低明显（P < 0.05）。MIL以剂量依赖性方式增加CBF（P < 0.001），导致DCI发生率降低（P = 0.008），且神经行为功能衰退的恢复情况优于对照组（P < 0.001）。第1天的CBF值预测DCI的临界值为42.5ml/100g/min（特异性82%，敏感性83%），MIL治疗的小鼠该值高于对照组（51.7对37.6ml/100g/min；P < 0.001）。
MIL可改善SAH后的急性灌注不足，从而预防DCI和功能恶化，作为一种针对早期脑损伤的神经心脏保护剂发挥作用。
