米力农对兔蛛网膜下腔出血后脑血管痉挛的作用及其机制研究

目的探讨米力农对兔蛛网膜下腔出血(SAH)后脑血管痉挛的作用及其机制。方法取3个月龄日本大耳白兔32只,随机分为SAH组、对照组、米力农组及米力农+N-硝基-左旋精氨酸甲酯(L-NAME)组,共4组,每组8只。采用枕大池二次注入自体血建立SAH模型。向对照组兔枕大池内注入等渗盐水替代自体血,其他操作同SAH组。在SAH造模后30 min,对米力农组兔由耳源静脉注射米力农溶液5 ml(30μg/kg);米力农+L-NAME组,先经耳源静脉注射米力农溶液(30μg/kg),再注射L-NAME(30 mg/kg),共5 ml;对照组、SAH组注射等渗盐水5 ml。对4组兔均连续给药3 d,1次/d。术后第3天应用CT血管造影(CTA)和经颅多普勒超声(TCD)观察各组兔基底动脉的管径和血流速度。结果 TCD检查显示,对照组、SAH组、米力农组、米力农+L-NAME组基底动脉的平均血流速度分别为(19.4±1.8)、(32.7±4.2)、(17.8±1.8)及(33.2±7.2)cm/s;收缩期峰值流速分别为(27±5)、(45±4)、(29±3)及(44±4)cm/s。CTA检查显示,4组基底动脉管径分别为(1127±140)、(772±116)、(1113±101)及(802±91)μm。上述指标各组间比较,差异均有统计学意义,P<0.01。结论米力农对SAH后脑血管痉挛有缓解作用,其扩血管作用可能与L-NAME抑制一氧化氮合酶活性有关。

Effect of milrinone on cerebral vasospasm after subarachnoid hemorrhage in rabbits and its pathogenesis study

Objective To investigate the effect of milrinone on cerebral vasospasm after subarach- noid hemorrhage （SAH） in rabbits and its pathogenesis. Methods A total of 32 3-month-old Japanese white rabbits were selected and randomly allocated into SAH, control, milrinone, and milrinone ± N-nitro-L-arginine methyl ester （L-NAME） groups （n = 8 in each group）. A SAH model was induced by double injection of autologous blood into the cisterna magna. Iisotonic saline was injected into the cisterna magna instead of autoblood in the control group. The others were the same as the SAH model group. At 30 minutes after SAH modeling, milrinone solution 5 mL （30 p,g/kg） were injected via ear vein in the milrinone group;and milrinone solution 5 mL （30 txg/kg） were injected first, then L-NAME 5 mL （30 μg/kg） were injected in the milrinone ± L-NAME group; 5 mL isotonic saline were injected in the control and SAH groups. The 4 groups were administered continuously for 3 days, once a day. CT angiography （CTA） and transcranial Doppler （TCD） were used to observe basilar artery diameter and blood flow velocity of the ani-mals in each group at day 3 after procedure. Results TCD examination showed that the mean flow veloci-ties of the basilar arteries in the control, SAH, milrinone, milrinone ± L-NAME groups were 19.4 ± 1.8, 32.7 ± 4.2, 17.8 ± 1.8, and 33.2 ± 7.2 cm/s, respectively; the peak systolic velocities were 27 ± 5, 45 ±4, 29 ± 3, and 44 ± 4 cm/s, respectively. CTA examination showed that the diameters of basilar arteries were 1127 ± 140, 772 ± 116, 1113 ± 101, and 802 ± 91 μm, respectively. In comparision with the above indicators among each group, the differences were statistically significant （P 〈0.01 ）. Conclusion M ilri- none has a mitigative effect on cerebral vasospasm after SAH, and its vasodilator effect may be associated with L-NAME inhibit the activities of carbon monoxide synthase.