不同靶目标低温治疗对心肺复苏大鼠循环功能及预后的影响

Effects of different target hypothermia treatment on the circulation function and prognosis of cardiopulmonary resuscitation rats

目的研究不同靶目标低温治疗对心肺复苏后大鼠循环功能及预后的影响。方法选取健康成年雄性清洁级SD大鼠44只,电刺激诱导大鼠室颤8 min后开始心肺复苏,复苏8 min后给予电除颤。共有28只大鼠心肺复苏成功,恢复自主循环后,将大鼠随机分入4组:37℃常温组、35℃低温组、33℃低温组及28℃低温组,每组7只。立即采用物理降温方式降温至靶目标温度,低温治疗4 h后开始复温至(37.0±0.2)℃,继续观察72 h。低温治疗期间及复温后监测心肺复苏大鼠平均主动脉压(MAP)、心率、射血分数(EF),颊黏膜微循环血流(MBF)、血乳酸(Lac)、生存时间、生存率及神经系统缺陷评分(NDS)等指标并进行组间比较。结果在复苏过程中,大鼠冠脉灌注压、电除颤次数、室颤-自主循环恢复时间差异均无统计学意义(P>0.05)。低温治疗期间,28℃组大鼠心率最低,37℃组心率最高;低温组MAP及EF值高于常温组,其中33℃组及28℃组EF值(%)明显高于35℃组(63.8±6.1,67.8±8.4 vs.54.0±5.2,P<0.05);33℃组及35℃组Lac值明显低于37℃组及28℃组(P<0.05);低温组MBF值低于常温组,3个低温组间MBF值差异无统计学意义(P>0.05)。复温后,35℃组大鼠EF值(%)明显高于其他组(52.9±3.3 vs.46.9±6.2,38.5±7.5,35.8±7.3,P<0.05);33℃组及35℃组MBF值与28℃组比较明显恢复(2.8±0.4,2.4±0.5 vs.1.6±0.6,P<0.05),33℃组与35℃组MBF值无明显差异(P>0.05)。35℃组及33℃组生存时间、生存率、NDS评分明显优于37℃组及28℃组(P<0.05),35℃组与33℃组比较差异无统计学意义(P>0.05)。结论靶目标温度为33℃及35℃的低温治疗可以保护心肺复苏后大鼠循环功能,减轻神经功能损伤,改善预后。35℃低温治疗可能是临床心跳骤停患者复苏后治疗的一个新选择。

Objective To investigate the effects of different target hypothermia on the cardiovascular function and prognosis of rats after cardiopulmonary resuscitation.Methods A total of 44 male SD rats were induced with electrical stimulation to ventricular fibrillation(VF)for 8 minutes,then cardiopulmonary resuscitation(CPR)was performed for 8 minutes followed by electric defibrillation(DF).Totally 28 SD rats survived VF,and randomized into either 37℃normothermia group,35℃hypothermia group,33℃hypothermia group or 28℃hypothermia group(7 each)after restoration of autonomic circulation(ROAC).Hypothermia was immediately induced with surface cooling to the target temperature.The target temperature was maintained for 4 hours before rewarming to(37±0.2)℃.Survived animals were observed for up to 72 hours.Mean aortic pressure(MAP),ejection fraction(EF),heart rate(HR),blood lactate level(Lac),microcirculation of buccal flow(MBF),duration of survival,survival rate and neurological deficit score(NDS)were measured during hypothermia and post-rewarming.Results During CPR,there were no difference in coronary perfusion pressure(CPP),times of DF,duration of VF-ROAC(P>0.05).During hypothermia treatment,the slowest HR was observed in the 28℃hypothermia group,and the highest HR was observed in the 37℃normothermia group;The levels of MAP and EF were higher in hypothermia groups than in normothermia group,among which the EF level(%)was obviously higher in 33℃hypothermia group and 28℃hypothermia group than in 35℃hypothermia group[(63.8±6.1,67.8±8.4)%vs.(54.0±5.2)%,P<0.05];the Lac level was markedly lower in 33℃hypothermia group and 35℃hypothermia group than in 37℃normothermia group and 28℃hypothermia group(P<0.05);the MBF levels were lower in hypothermia groups than in normothermia group,while no statistical significant difference existed in MBF level among the 3 hypothermia groups(P>0.05).After rewarming,the EF level was markedly higher in 35℃hypothermia group than in the 33 other groups[(52.9±3.3)%vs.(46.9±6.2,38.5±7.5,35.8±7.3)%,P<0.05];MBF was obviously recovered in 33℃and 35℃hypothermia groups compared with that in 28℃hypothermia group[(2.8±0.4,2.4±0.5)vs.(1.6±0.6),P<0.05],but no difference existed between 33℃and 35℃hypothermia group.The duration of survival,survival rate and NDS score were much better in 33℃and 35℃hypothermia groups than in 28℃hypothermia groups and 37℃normothermia group,but no difference between 33℃and 35℃hypothermia groups(P<0.05).Conclusions Hypothermia therapy with 33℃and 35℃target temperature may protect the blood circulation function of rats after CPR,reduce nerve function injury and improve prognosis.Hypothermia therapy with 35℃target temperature might be a new choice for treatment of patients with clinical cardiac arrest after recovery.