电刺激迷走神经对失血性休克犬微循环的影响

Effects of electrical stimulation of vagus nerve on microcirculation in dogs with hemorrhagic shock

目的采用电刺激迷走神经激活胆碱能抗炎通路,观察电刺激迷走神经对失血性休克犬的保护作用,并探讨其作用机制。方法 30条健康杂种犬随机分为假失血休克组(SHAM组)、休克组(HEM组)、迷走神经切断组(VGX组)、迷走神经刺激组(STM组)、胆碱酯酶抑制组(THA组)5组,每组6条。采用股动脉快速放血法制作失血性休克模型,将左侧迷走神经远端连接刺激电极,于制模成功即刻(0 min),以5 V、2 ms、1 Hz强度的电压持续电刺激30 min。各组犬均行经右颈外静脉置入5F Swan-Ganz漂浮导管,股动脉置管,经压力传感器连接多功能监测仪,股静脉置管备用。使模型稳定40 min,记录血流动力学指标,在休克前、0 min和180 min时分别取股动脉血检测乳酸值,模型制备完成后每小时记录1次尿量。并记录氧供和氧耗的数值。组间比较采用单因素方差分析。结果制模成功后,SHEM组平均动脉压MAP(mmHg)高于其余4组[(121.30±8.66)、(40.70±0.82)、(41.30±1.21)、(40.50±1.23)、(41.20±1.17),F=110.156,P<0.01],STM组和THA组在90 min时MAP(mmHg)高于HEM组[(65.30±10.63)、(59.30±5.85)、(54.00±5.66),F=105.649,P<0.01]。犬血乳酸值(mmol/L)在0 min时HEM组高于SHAM组[(5.58±0.57)、(0.79±0.18),F=51.454,P<0.01],在180 min时HEM组高于SHAM、STM及THA组[(9.93±2.04)、(0.86±0.14)、(3.19±0.42)、(3.50±1.12),F=75.875,P<0.01]。120 min及180 min时除SHAM组外其余组尿量均减少,但STM组和THA组均高于HEM组[(11.00±1.80)、(10.00±1.20)、(7.00±1.00) ml/h;(11.00±1.00)、(9.00±1.20)、(4.00±0.82) ml/h]差异均有统计学意义(F=79.772、129.037,P<0.01)。180 min时除SHAM组外,犬血中氧供及氧耗均降低,STM组和THA组氧供[(284.0±14.8)、(260.7±18.1) ml/min]HEM组[(179.1±7.5) ml/min],差异有统计学意义(F=2 375.026,P<0.01);HEM、VGX、STM和THA组氧耗[(73.6±6.6)、(71.5±4.3)、(78.4±3.2)、(73.6±9.2) ml/min]均低于SHAM组[(138.0±18.4) ml/min],差异有统计学意义(F=48.667,P<0.01)。结论电刺激迷走神经对失血性休克具有潜在的保护作用,其机制可能与激活胆碱能抗炎通路有关。

Objective To investigate the protective effect of electrical stimulation of vagus nerve through the cholinergic anti-inflammatory pathway against haemorrhagic shock in dogs.Methods Thirty healthy dogs were randomly divided into five groups:SHAM group,HEM group,VGX group,STM group,and THA group.HEM was induced by intermittent with drawing of blood until MAP stabibilzed for 40 minutes within the range 40 mmHg(1 mmHg=0.133 kPa).The left vagus nerve trunk was placed across bipolar platinum electrodes connected to stimulation module and controlled by an acquisition system.Stimuli with constant voltage(5 V,2 ms,1 Hz)were applied to the nerve for 30 minutes.Before stimulation,the common carotid artery was implanted into a blood pressure transducer for continuous registration of mean arterial blood pressure(MAP)and pulmonary artery was implanted into a thermodilution balloon catheter.Blood samples of these dogs were collected in all groups after stimulation.Urine output was recorded every hour.The changes of the arterial blood-gas levels and the oxygen delivery(DO2)and the oxygen consumption(VO2)were observed.The comparison of intergroup was performed by One-way Analysis of Variance.Results MAP(mmHg)was significantly higher in SHAM group(121.30±8.66)than that in the other four groups[(40.70±0.82),(41.30±1.21),(40.50±1.23),(41.20±1.17),F=110.156,P<0.01]at 0 min,it was also higher in STM group and THAgroup at 90 min(65.30±10.63),(59.30±5.85)than that in HEM group(54.00±5.66,F=105.649,P<0.01).The blood lactate(mmol/l)was significantly higher(5.58±0.57)in HEM group than that in SHAM group(0.79±0.18,F=51.454,P<0.01)at 0 min,it was also significantly higher(9.93±2.04)in HEM group at 180 min than that in group SHAM,STM and THA[(0.86±0.14),(3.19±0.42),(3.50±1.12),F=75.875,P<0.01].At 120 min and 180 min,urine volume decreased in all groups except SHAM group,but it was significantly more in both STM group and THA group than that in HEM group[(11.00±1.80),(10.00±1.20),(7.00±1.00)ml/h;(11.00±1.00),(9.00±1.20),(4.00±0.82)ml/h,F=79.772,129.037,P<0.01].Except SHAM group,the oxygen supply and oxygen consumption of dogs decreased at 180 min.The oxygen supply was higher in STM group and THA group[(284.0±14.8),(260.7±18.1)ml/min,F=2375.026,P<0.01]than that in HEM group[(179.1±7.5)ml/min].The oxygen consumption was significantlylower in HEM group,VGX group,STM group and THA group[(73.6±6.6),(71.5±4.3),(78.4±3.2),(73.6±9.2)ml/min]than that inSHAM group[(138.0±18.4)ml/min,F=48.667,P<0.01].Conclusion The results suggested that the cholinergic anti-inflammatory pathway might produce a potential protective effect on hemorrhagic shock in dogs.The pathway can inhibit the release of inflammatory cytokines significantly and rapidly and attenuate systemic inflammatory response.