自主循环恢复后轻度低温对心室纤颤兔心功能和心肌结构的影响

目的 观察轻度低温干预对心室纤颤(室颤)兔自主循环恢复(ROSC)后心脏功能、心肌结构和48 h存活率的影响.方法 将新西兰兔按随机数字表法分为4组,采用心外膜电刺激致颤4 min行心肺复苏(CPR)复制动物CPR模型,ROSC后即分别给予常温(39.0±0.5)℃,n=10]和低温(33.5±0.5)℃,n=10]处理;同时设常温(n=8)和低温(n=8)对照.各组均监测4h血流动力学指标,观察48 h存活情况;取心肌组织进行病理学观察,检测细胞凋亡原位末端缺刻标记法(TUNEL)];测定左室心尖组织ATP、ADP、AMP含量高效液相色谱(HPLC)法],并计算心肌能荷(EC).结果 ①血流动力学:低温对照组和常温对照组比较,心率(HR)、左室压力下降最大速率(-dp/dt max)在基线后各时间段均有下降;左室压力上升最大速率(+dp/dt max)和平均动脉压(MAP)在0.5h有显著差异,而在其他时段均无差异;左室舒张期末压(LVEDP)、左室收缩期末压(LVESP)和股动脉收缩压(SBP)、舒张压(DBP)在各时间段均无显著差异.②复苏后低温组与复苏后常温组比较,HR(次/min)和-dp/dt max(mm Hg/s)在ROSC后0.5、1、2、3、4h均有下降(HR:216.5±33.3比292.9±38.4,218.2±28.0比294.3±37.0,227.5±25.4比291.4±25.3,232.4±27.4比278.1±30.8,230.6±22.0比285.1±38.2;-dp/dt max:1 847.1±241.2比2 383.3±470.9,1 860.7±167.8比2 154.6±319.5,1 822.3±389.7比2 239.7±379.0,1 950.6±412.9比2 229.6±392.4,1 875.7±555.6比2 396.7±420.1,均P＜0.05); LVEDP、+dp/dt max、LVESP、股动脉血压(SBP、DBP、MAP)在ROSC后各时间点均无显著差异.③复苏后低温组48h心肌组织形态损害较复苏后常温组轻.④复苏后低温组心肌细胞凋亡指数(AI)低于复苏后常温组(26.39％比42.02％,P＜0.05).⑤能量检测:复苏后低温组ATP含量(μmol/g)高于复苏后常温组(0.97±0.26比0.65±0.16,P＜0.05).复苏后常温组EC明显低于常温对照组和低温对照组(0.33±0.13)％比(0.52±0.12)％、(0.55±0.06)％,均P＜0.05],而复苏后低温组EC(0.41±0.12)％]与两对照组无显著差异.⑥复苏后低温组48 h存活率高于复苏后常温组(100％比60％,P=0.043).结论 室颤兔ROSC后存在心肌结构损害和心功能下降;轻度低温干预可降低48 h死亡率,其保护机制可能与抑制复苏后心肌细胞进一步的损害和凋亡有关;轻度低温对心功能无明显直接抑制,也不引起血流动力学恶化.

The effects of mild hypothermia on cardiac function and myocardial structure in a rabbits model of ventricular fibrillation after restoration of spontaneous circulation

Objective To examine the impact of mild hypothermia on cardiac function,myocardial tissue integrity,and 48 hours mortality in a rabbits model of ventricular fibrillation after restoration of spontaneous circulation(ROSC).Methods The rabbits were randomly divided into four groups:normothermic post ROSC(NTPR,n=10),mild hypothermia post ROSC(HTPR,n=10),normothermic control(NTC,n=8)and mild hypothermia control(HTC,n=8).Ventricular fibrillation was induced by trans-epicardium electric-shook with alternating current in all the animals and ROSC was achieved through administration of adrenaline(i.v.)and artificial ventilation in group NTPR and HTPR.The body temperature of the animals was kept either at(39.0±0.5)℃(NTPR and NTC)or(33.5±0.5)℃(HTPR and HTC)for 4 hours after surgery for hemodynamic indexe data collection 0.5,1,2,3 and 4 hours after surgery,48 hours later,the mortality in the animals was recorded,and myocardial tissue samples were collected from survivaed animals for morphological examination by light and electric microscopy and analysis of apoptosis by terminaldeoxynucleoitidyl transferase mediated nick end labeling(TUNEL)staining.The content of ATP,ADP and AMP in the tissue samples was measured by high performance liquid chromatography(HPLC)for the calculation of energy charges(EC).Results ①Hemodynamic indexes:as compared to the NTC group,HTC group exhibited significantly lower levels of heart rate(HR)and-dp/dt max in all the time points.No significant difference between the two groups in the levels of +dp/dt max and mean artery pressure(MAP)was found in all the time points but 0.5 hour.There was no significant difference in the levels of left ventricular end-diastolic pressure(LVEDP),left ventricular end-systolic pressure(LVESP),and femoral artery blood pressure between the two groups.② In comparison with NTPR group,HTPR group exhibited significantly(all P＜0.05)lower levels of HR(bpm)and-dp/dt max in all time points(ROSC 0.5,1,2,3,4 hours:HR 216.5±33.3 vs.292.9±38.4,218.2±28.0 vs.294.3±37.0,227.5±25.4 vs.291.4±25.3,232.4±27.4 vs.278.1±30.8,230.6±22.0 vs.285.1±38.2;-dp/dt max 1 847.1±241.2 vs.2383.3±470.9,1 860.7±167.8 vs.2 154.6±319.5,1 822.3±389.7 vs.2 239.7±379.0,1 950.6±412.9 vs.2 229.6±392.4,1 875.7±555.6 vs.2 396.7±420.1).There was no significant difference between the two groups in the levels of LVEDP,+dp/dt max,LVESP,and femoral artery blood pressure.③Optical and electron microscopy revealed myocardium injury in samples from animals underwent ROSC.However,in comparison with the NTPR group,samples from HTPR group exhibited less damage to the myocardium structure.④ Apoptosis index(AI)of myocardium was significantly(P＜0.05)higher in NTPR group(42.02％)than in HTPR group(26.39％).⑤ Tests of myocardial energy:ATP level(μmol/g)in HTPR was significantly(P＜0.05)higher than NTPR(0.97±0.26 vs.0.65±0.16).EC in NTPR was significant lower than it in two control groups(0.33±0.13)％ vs.(0.52±0.12)％,(0.55±0.06)％,both P＜0.05],whereas no such difference was found between HTPR(0.41±0.12)％]and two control groups.⑥ 48 hours survival rate in HTPR group was significantly higher(P=0.043)as compared to NTPR group (100％ vs.60％).Conclusions Myocardial dysfunction and myocardium tissue injury both develop in post-resuscitation rabbits with ventricular fibrillation.In these animals,reducing body temperature to the level of mild hypothermia after ROSC may improve the 48 hours survival rate,probably via mechanisms that suppress myocardial cell apoptosis.In our study,such intervention produced no obvious negative impact neither on the cardiac function nor hemodynamics.