目的探讨利多卡因(lidocaine)经兔腹主动脉局部灌注减轻脊髓缺血再灌注损伤(ischemia-reperfusion injury,IRI)的作用及最佳保护剂量。方法新西兰大耳白兔40只,随机分为5组(n=8):生理盐水对照组(NS组)、利多卡因10 mg/kg组(L10组)、利多卡因20 mg/kg组(L20组)、利多卡因40 mg/kg组(L40组)和利多卡因80 mg/kg组(L80组)。全麻下开腹阻断左肾动脉远端的腹主动脉及双侧髂总动脉30 min,构建脊髓缺血模型,自缺血即刻起分别向阻断的腹主动脉段内灌注生理盐水(NS组)和不同剂量的利多卡因溶液(L10~L80组),持续30 min后停止,同时开放腹主动脉及双侧髂总动脉行再灌注,观察血液动力学变化,并于动物清醒即刻、再灌注6、24和48 h按Tarlov标准进行神经行为学评分。全麻下取出L4~L6脊髓,光镜下观察脊髓前角组织形态并计数正常运动神经元。结果与NS组比较,利多卡因组神经行为学评分及脊髓前角正常运动神经元计数均增高,其中L40组最高(P〈0.05)。L80组有2例动物在腹主动脉开放后出现心率显著减慢。与其他各组比较,L80组再灌注期间平均动脉压降低(P〈0.05)。结论利多卡因经腹主动脉局部灌注可减轻兔脊髓IRI,其保护作用与剂量密切相关。利多卡因80 mg/kg将导致严重并发症,我们认为最佳保护剂量为40 mg/kg。
Objective This study was designed to investigate the effect and optimum dosage of lidocaine when infused through aorta to pretect the spinal cord against ischemia reperfusion injury(IRI) in rabbits. Methods Forty New Zealand white rabbits were divided randomly into 5 groups(n=8): one control group of normal saline(NS group) and 4 lidocaine groups at different doses of 10,20,40 and 80 mg/kg respectively(L10,L20,L40 and L80 groups).Spinal cord ischemia was induced by clamping the abodomial aorta just bellow the left renal artery combined with simultaneously clamping bilateral common iliac arteries for 30 minutes.A catheter was inserted into abdominal aorta close to the site of occlusion via femoral artery.Right after the cross-clamping,the rabbits received regional infusion of normal saline and different doses of lidocaine solution via the catheter into the clamped aorta.Half an hour later,the abdominal aorta and the bilateral common iliac arteries were unclampted for reperfusion.The hemodynamic changes were monitored and neurological status was assessed according to the modified Tarlov scale system at the moment of emergence and 6,24 and 48 hours after the reperfusion.Lumbar segments of the spinal cord(L4-L6) were removed at 48 hours after reperfusion for pathological examination,and the total number of normal motor neurons in the anterior horn were counted. Results Compared with control group,regional lidocaince infusion significantly improved the Tarlov scores and numbers of normal motor neurons,and lidocaine 40 mg/kg functioned the most effetive(P0.05).The heart rates of two rabbits decreased significantly in L80 group.Compared with other lidocaine groups,mean arterial pressure decreased in L80 group during the reperfusion(P0.05). Conclusions Regional infusion of lidocaine during clamping process can provide significant protection to the spinal cord against IRI in rabbits,and the most optimum dosage is 40 mg/kg in the research.