Phenylephrine Ameliorates Cerebral Cytotoxic Edema and Reduces Cerebral Infarction Volume in a Rat Model of Complete Unilateral Carotid Artery Occlusion with Severe Hypotension
Phenylephrine Ameliorates Cerebral Cytotoxic Edema and Reduces Cerebral Infarction Volume in a Rat Model of Complete Unilateral Carotid Artery Occlusion with Severe Hypotension
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DOI：
10.1213/ane.0b013e31819d94e3
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发表时间：
2009-05-01
影响因子：
5.7
通讯作者：
Makita, Koshi
中科院分区：
文献类型：
--
作者：
Ishikawa, Seiji;Ito, Hiroyuki;Makita, Koshi
背景：苯肾上腺素是一种选择性肾上腺素能受体激动剂，可通过收缩外周血管来增加动脉血压。然而，苯肾上腺素是否能改善失血性休克期间颈内动脉疾病患者的脑缺血预后尚不清楚。(实验1)成年雄性SD大鼠21只，用异氟醚麻醉，机械通气。结扎右侧颈总动脉后，抽动脉血至平均动脉压(MAP)达到30 mm Hg，造成脑缺血。MAP维持在30 mm Hg10min后，动物随机分为3组，每组7只。苯肾上腺素组静脉注射苯肾上腺素维持MAP为70+/-3 mm Hg，持续5分钟。生理盐水组连续给予等量生理盐水5min。对照组不注射苯肾上腺素或生理盐水，MAP维持在30 mm Hg。在失血30min时，以0.25mL/min的速度静脉回输。连续采集弥散加权磁共振图像，建立表观扩散系数图，以确定细胞毒性水肿的体积。(实验2)为分析苯肾上腺素对右侧大脑中动脉区局部脑血流量的影响，用激光多普勒血流仪测定了15只大鼠(n=5)的局部脑血流量。结果：(实验1)失血10min时，去氧肾上腺素组(357.5±93.5mm3)、生理盐水组(333.5+/-69.6mm3)和对照组(303.1+/-85.8mm3)之间细胞毒性水肿体积差异无统计学意义。对照组低扩散系数区随时间延长明显扩大，而去甲肾上腺素组低扩散系数区在注射苯肾上腺素后即开始缩小，30min内几乎全部消失。去甲肾上腺素组最终脑梗塞体积(3.90±-2.6mm3)显著低于生理盐水组(341.5±-21.3.7mm3)和对照组(509.1+/-197.0 mm(3))。(实验2)虽然rCBF在失血10min时下降到基线的40%-50%，但苯肾上腺素立即使rCBF高于基线水平。生理盐水组rCBF显著增加，但与苯肾上腺素组相比有一定延迟。结论：苯肾上腺素可减轻大鼠一侧颈动脉完全闭塞伴重度低血压时的细胞毒性水肿，缩小脑梗塞体积。这些发现表明，在失血性休克期间，苯肾上腺素短暂地增加了脑血流量，而不增加脑血管张力。
BACKGROUND: Phenylephrine is a selective a, adrenergic receptor agonist that increases arterial blood pressure by peripheral vasoconstriction. However, whether phenylephrine improves the Outcome of cerebral ischemia in patients with internal carotid artery disease during hemorrhagic shock is unclear.METHODS: (Experiment 1) Twenty-one adult male Sprague-Dawley rats were anesthetized with isoflurane and their lungs mechanically ventilated. After the right common carotid artery was ligated, arterial blood was withdrawn until mean arterial blood pressure (MAP) reached 30 mm Hg to induce cerebral ischemia. After MAP was maintained at 30 mm Hg for 10 min, the animals were randomly allocated to three groups (n = 7 each). in the phenylephrine group, phenylephrine was administered IV to maintain a MAP of 70 +/- 3 mm Hg for 5 min. in the saline group, an identical volume of normal physiologic saline was continuously administered for 5 min. In the control group, neither phenylephrine nor saline was administered and MAP was maintained at 30 mm Hg. At 30 min of exsanguination, the withdrawn blood was reinfused IV at a rate of 0.25 mL/min. Diffusion-weighted magnetic resonance images were serially acquired and apparent diffusion coefficient maps were created to determine the volume of cytotoxic edema. (Experiment 2) To analyze the effect of phenylephrine on the regional cerebral blood flow (rCBF) in the right middle cerebral artery territory, rCBF was measured using laser Doppler flowmetry in 15 additional rats (n = 5 each).RESULTS: (Experiment 1) At 10 min of exsanguination, there were no significant differences in the volume of cytotoxic edema among the phenylephrine (357.5 +/- 93.5 mm(3)), saline (333.5 +/- 69.6 mm(3)), and control (303.1 +/- 85.8 mm(3)) groups. Low apparent diffusion coefficient regions significantly expanded with time in the control group, whereas they started to decrease just after phenylephrine infusion and almost all had disappeared within 30 min in the phenylephrine group. The final infarction volume in the phenylephrine group (3.9 +/- 2.6 mm(3), P < 0.01) was significantly lower than that in the saline group (341.5 +/- 21.3.7 mm(3)) and control group (509.1 +/- 197.0 mm(3)). (Experiment 2) Although rCBF decreased to 40%-50% of the baseline at 10 min of exsanguination, phenylephrine immediately increased rCBF over the baseline level. In the saline group, rCBF increased significantly, but there was some delay compared with the phenylephrine group.CONCLUSIONS: Phenylephrine ameliorated cytotoxic edema and decreased the infarction volume in a rat model of complete Unilateral carotid artery occlusion with severe hypotension. These findings suggest that phenylephrine transiently increased CBF Without increasing the tonus of cerebral vasculature during hemorrhagic shock.