丙戊酸钠对无液体复苏时致死性失血性休克犬平均动脉压和死亡率的改善作用

The effect of valproic acid in improving mean arterial pressure and mortality in dogs with lethal hemorrhagic shock devoid of fluid resuscitation

目的:研究丙戊酸钠对致死性失血性休克犬平均动脉压(MAP)和失血后72 h死亡率的影响。方法:成年雄性Beagle犬15只,先期无菌手术行颈总动脉、颈外静脉及膀胱置管,24 h后按全身血容量的40%放血制作失血性休克模型。按失血后24 h内处理不同随机分为休克对照组(n=8)和丙戊酸钠组(n=7)。休克对照组失血24 h内无治疗;丙戊酸钠组于失血后1.5 h静脉注射丙戊酸钠(100 mg/kg)。失血后24 h起两组犬均实施静脉补液。测定犬失血前和失血后2、4、8、24、48和72 h非麻醉状态下的MAP和心率(HR),记录每24 h尿量和失血后72 h死亡率。结果:休克对照组MAP失血后4 h达最低,仅为失血前水平的38.4%;HR失血后2 h最高,为失血前的175.8%。失血后,丙戊酸钠组MAP高于休克对照组,4、8和24 h差异显著(P<0.05或P<0.01);失血后2 h起HR始终低于休克对照组(P<0.05或P<0.01)。失血后48 h丙戊酸钠组MAP和HR均恢复至失血前水平。丙戊酸钠组失血后8～24 h休克对照组5例无尿;丙戊酸钠组2例无尿。丙戊酸钠组0～24 h、24～48 h和48～72 h尿量均显著多于休克对照组(P<0.05),但两组48～72 h尿量仍显著低于失血前水平。丙戊酸钠组失血后72 h死亡率(28.6%,2/7只)显著低于休克对照组(62.5%,5/8只,P<0.05)。结论:犬40%血容量失血后静注丙戊酸钠能有效提高MAP,增加尿量,降低早期死亡率;丙戊酸钠有潜力成为无液体复苏条件下(战争或突发事故及灾害时)救治低血容量休克的有效药物。

Objective： To investigate the effect of valproic acid on mean arterial pressure （MAP） and mortality 72 hours after hemorrhage in dogs devoid of fluid resuscitation. Methods.. Fifteen male Beagle dogs were surgically prepared for cannulation of the carotid artery,jugular vein and urinary bladder,and 24 hours later they were subjected to approximately 40 % of total blood volume loss to reproduce a lethal hemorrhagic shock model Animals were randomly divided into two groups： shock control group （SC group, n = 8）, valproic acid treatment group （VAP group,n： 7）. Dogs in VAP groups received intravenous injection of valproic acid （100 mg/kg） 1.5 hours after bleeding,while those in SC groups were not given any treatment. Dogs in both groups were given intravenous fluid resuscitation beginning from 24 hours after bleeding. The MAP and heart rate （HR） were determined before hemorrhage （0 h） and 2,4,8,24,48 and 72 hours after hemorrhage without receiving anesthesia. Urinary output of each day and mortality rate at 72 hours after hemorrhage were also recorded. Results： MAP of SC group reached the trough level at 4 hours after hemorrhage and HR reaching peak level at 2 hours, which were only 38.40% and 175.8% of the levels at 0 hour respectively. The levels of MAP in VAP group were higher than those of SC group with statistically significant difference at 4,8 and 24 hours after hemorrhage（P〈0.05 or P〈0.01）. HR in VAP group was significantly lower than that of SC group from 2 hours on after bleeding （P〈0.05 or P〈0.01）. MAP and HR in VAP group recovered to those of 0 hour at 48 hours. Five dogs of SC group and 2 of VAP group showed anuria during 8-24 hours after hemorrhage. Urinary output of VAP group was significantly higher than that of SC group during the period of 0-24 hours,24-48 hours and 48-72 hours after loss of blood（P^0.05）, but the amount of urinary output of both groups was still lower than that before loss of blood. The mortality at 72 hours of VAP group was significantly lower than that of SC group（2/7（28.6%） vs. 5/8 （62.5%）, P〈0. 05]. Conclusion： The results indicate that intravenous injection of VAP promote MAP and urinary output,and it lowers the mortality of dogs suffering from a 40% blood volume loss. There for it might be an effective drug to treat hypovolemic shock,especially in warfront or sites of mass casualties with restricted medical resources.