异丙酚腹主动脉灌注和静脉输入在兔脊髓组织内药物浓度的比较

COMPARISON OF PROPOFOL CONCENTRATION IN THE SPINAL CORD BETWEEN INTRA-AORTIC AND INTRAVENOUS INFUSION

目的测定腹主动脉灌注与静脉输入异丙酚在缺血再灌注脊髓损伤组织内的药物浓度,探讨其可能的作用部位。方法取健康4～6月龄新西兰大白兔46只,体重2.0～2.5kg,随机分为生理盐水组(N组,n=10)、异丙酚腹主动脉灌注组(A组,n=18)、异丙酚静脉输入组(V组,n=18)组。建立肾下腹主动脉阻断脊髓缺血再灌注损伤模型,A组经腹主动脉阻断远端持续泵入异丙酚(50mg/kg)30min,N组泵入同等容量的生理盐水,V组经静脉持续泵入异丙酚(50mg/kg)30min。测定再灌注即刻A组和V组L4～6节段和T6～8节段的脊髓组织中异丙酚浓度,观察再灌注后48h3组动物的神经行为学评分和组织病理学变化,并计数脊髓前角正常神经元。结果3组在腹主动脉阻断后平均动脉压均有一定程度的降低,其中V组降低幅度最明显,阻断5min后显著低于N组,阻断10min后低于同时间点A组(P<0.05);A组在阻断15min后显著低于N组(P<0.05)。N、A组组内不同时间点心率与基础心率比较差异无统计学意义(P>0.05);V组于阻断期间心率增加明显,于阻断15min开始心率明显高于同时间点的N组和A组(P<0.05)。A组与N组间心率比较差异无统计学意义(P>0.05)。A组L4～6节段脊髓组织异丙酚浓度为(26950.5±30242.3)ng/g,显著高于T6～8节段的(3587.4±2479.3)ng/g、V组L4～6节段的(3045.9±2252.9)ng/g及T6～8节段的(3181.1±1720.9)ng/g,比较差异有统计学意义(P<0.05)。神经行为学观察显示,A组动物术后截瘫率为30%,明显低于N组的80%和V组的100%,差异有统计学意义(P<0.05);N、V组间比较差异无统计学意义(P>0.05)。A组脊髓前角正常神经元计数为8.4(4.0～11.5),明显多于N组的2.2(0～4.3)和V组的1.9(0～4.0),差异有统计学意义(P<0.05),N、V组间比较差异无统计学意义(P>0.05)。结论异丙酚腹主动脉灌注较静脉输入能获得更高的靶器官药物浓度,对缺血再灌注损伤脊髓具有更好的保护作用。

Objective To investigate the effect of propofol intra-aortic and intravenous infusion on the concentration of propofol for an ischemia-reperfusion spinal cord injury in rabbits. Methods Forty-six healthy adult New Zealand white rabbits were randomly divided into 3 groups： saline infusion group （group N, n=10）, propofol intra-aortic infusion group （group A, n=16） and propofol intravenous infusion group （group V, n=16）. The infrarenal abdominal aorta was occluded for 30 min during which propofol 50 mg/kg was infused continuously intra-aortic or intravenous with a pump in group A and V. In group N, the same volume of normal saline was infused in the same way and at the same rate as in group A. Upon reperfusion, propofol concentration of the spinal segments of L4-6 and T6-8 was examined in group A and V. At 48 hours after reperfusion, the neurological outcomes were recorded in each group. Results Mean blood pressure in group V from the time of 5 minutes after occlusion decreased more than in group N （P 〈 0.05） and than in group A from the time of 10 minutes after occlusion（P 〈 0.05）. The mean blood pressure in group N increased more than in group A from 15 minutes after occlusion （P 〈 0.05）. The heart rate increased more in group V from 10 minutes after occlusion than in group N and A （P 〈 0.05） in which no difference was observed. The propofol concentration in L4-6 of group A （26 950.5± 30 242.3） ng/g was higher than that in T6-8 of group A （3 587.4 _＋2 479.3） ng/g and both L4-6 （3 045.9 ±2 252.9） ng/g and T6-8 （3 181.1 ± 1 720.9） ng/g of group V（P 〈 0.05）. The paraplegia incidence was lower （30%） and the median of normal neurons was higher （8.4） in group A than in group N （80%, 2.2） and group V（100%, 1.9）, （P 〈 0.05）. There was no significant difference in group N and V in paraplegia incidence and the median of normal neurons （P 〉 0.05）. Conclusion Intra-aortic infusion shows a better neurological outcome than intravenous infusion and could contribute to higher concentration of propofol in the ischemia spinal cord.