氢溴酸山莨菪碱可改善复苏后机体微循环

Anisodamine hydrobromide can improve microcirculation after resuscitation

目的探讨复苏后机体微循环改变特点及氢溴酸山莨菪碱对机体的保护作用机制。方法将24只北京白猪随机分为3组,即氢溴酸山莨菪碱组(AH组,8只),生理盐水组(Saline组,8只)及假手术组(Sham组,8只)。对AH组及Saline组动物应用电刺激诱导室颤,在室颤8 min后给予心肺复苏至恢复自主循环(recover the spontaneous circulation,ROSC)。Saline组复苏后仅给予盐水静点,AH组给予盐水+氢溴酸山莨菪碱静点。留取6个时间点(基础状态,ROSC即刻,ROSC1 h,ROSC2 h,ROSC4 h及ROSC 6 h)的动静脉血液,分别检测血气分析及细胞因子IL-4及IFN-γ,并检测各时间点的微循环指标PVD及MFI,同时测量连续心输出量(cardiac output,CO),全心射血分数(global ejection fraction,GEF)。分析3组之间上述指标的差异。结果复苏后,PVD与MFI在肠道及舌下部位均明显下降(与基线和假手术组相比,P<0.05)。自复苏后2 h开始,AH组与Saline组肠道PVD(12.09±0.75vs.11.23±0.53,14.53±0.69 vs.13.43±0.44,16.28±0.44 vs.15.53±0.50),肠道MFI(2.45±0.12 vs.2.31±0.16,2.70±0.10 vs.2.53±0.13,2.91±0.64 vs.2.67±0.14),舌下PVD(7.92±0.61 vs.7.09±0.84,9.52±0.92vs.8.29±1.25,11.10±0.97 vs.9.95±1.14),舌下MFI(2.28±0.06 vs.2.15±0.13,2.60±0.09 vs.2.30±0.35,2.85±0.03 vs.2.55±0.415)进行比较,均差异有统计学意义(P<0.05)。肠道微循环血流量的变化与舌下微循环血流量的变化密切相关(PVD:r=0.864,P<0.01;MFI:r=0.915,P<0.01)。同时,复苏后机体心脏功能受损,细胞因子IFN-γ及IL-4水平异常,提示免疫失衡存在,AH组与Saline组相比,CO及GEF恢复更快且有利于维持IFN-γ/IL-4稳态。结论肠道微循环在复苏后将出现功能损伤,其严重程度与心功能障碍成正相关,舌下微循环的测量可以反映肠道微循环的变化,复苏后细胞因子变化表现为免疫失衡,应用氢溴素山莨菪碱可以改善这种失衡,有利于心脏功能恢复,推测与该药物可以改善微循环有关。

Objective To investigate the characteristics of microcirculatory changes after resuscitation and the protective mechanism of anisodamine hydrobromide on the body.Methods Twenty-four Beijing white pigs were randomly divided into three groups:anisodamine hydrobromide group(AH group,8 pigs),saline group(Saline group,8 pigs)and sham operation group(Sham group,8 pigs).Electric stimulation was used to induce ventricular fibrillation in AH group and Saline group,and cardiopulmonary resuscitation was given to recover the spontaneous circulation(ROSC)after 8 minutes ventricular fibrillation.The Saline group was only given saline after ROSC,and the AH group was given saline and anisodamine hydrobromide.The arterial and venous blood was collected at six time points:the baseline,ROSC instant,ROSC 1 h,ROSC 2 h,ROSC 4 h and ROSC 6 h,and the blood gas analysis and cytokine IL-4 and IFN-γwere measured respectively.The microcirculation indexes PVD and MFI,continuous cardiac output(CO)and global ejection fraction(GEF)were measured at each time point.Analyzed the differences of these indicators among the three groups.Results After resuscitation,PVD and MFI decreased significantly in both intestinal and sublingual regions(compared with baseline and sham operation groups,P<0.05).From 2 hours after resuscitation,there were significant differences between AH group and Saline group:intestinal PVD(12.09±0.75 vs.11.23±0.53,14.53±0.69 vs.13.43±0.44,16.28±0.44 vs.15.53±0.50,P<0.05),intestinal MFI(2.45±0.12 vs.2.31±0.16,2.70±0.10 vs.2.53±0.13,2.91±0.64 vs.2.67±0.14,P<0.05),Sublingual PVD(7.92±0.61 vs.7.09±0.84,9.52±0.92 vs.8.29±1.25,11.10±0.97 vs.9.95±1.14,P<0.05)and sublingual MFI(2.28±0.06 vs.2.15±0.13,2.60±0.09 vs.2.30±0.35,2.85±0.03 vs.2.55±0.415,P<0.05).The change of intestinal microcirculation was closely related to the change of sublingual microcirculation(PVD:r=0.864,P<0.01;MFI:r=0.915,P<0.01).Meanwhile,after resuscitation,the cardiac function was damaged,and the change of levels of IFN-γand IL-4 indicated immune imbalance.Compared with Saline group,CO and GEF in AH group recovered faster and AH can help body to maintain IFN-γ/IL-4 steady state.Conclusion The severity of intestinal microcirculation dysfunction after resuscitation is closely related to the cardiac function,the sublingual microcirculation can reflect the changes of intestinal microcirculation,and the changes of cytokines after resuscitation show an immune imbalance.Anisodamine hydrobromide can improve this imbalance,and repair the cardiac function,it can be inferred that these effects are related to the ability of this drug to improve microcirculation.