右美托咪啶对离体兔心缺血再灌注后丙二醛、三磷酸腺苷及乳酸含量的影响

Effects of dexmedetomidine on the content of malondialdehyde,adenosine triphosphate and lactic acid after ischemia-reperfusion in isolated rabbit hearts

目的观察右美托咪啶对家兔离体心脏缺血再灌注损伤后丙二醛、三磷酸腺苷及乳酸含量的影响,探讨其对缺血再灌注损伤心肌的保护作用。方法健康成年家兔18只,成功制备Langendorff离体心脏灌注模型,KH液平衡灌流15min后,随机分为三组(n=6),空白对照组(C组):持续平衡灌注37℃K-H液150min;缺血/再灌注组(I/R组):K-H液继续灌流15min后停灌,注射Thomas液(4℃,10mL/kg)使心脏停搏60min,心脏周围用低温(4℃)Thomas液保护,30min复灌Thomas液(4℃,5mL/kg),60min时恢复K-H液灌流使心脏复跳;右美托咪啶组(DEX组):于K-H液及Thomas液中加入DEX(25ng/mL),余同I/R组。记录平衡灌流15min(T_0),继续灌流15min/平衡30min(T_1),复灌30min(T_2)/平衡120min,复灌60min/平衡150min(T_3)的心率(HR)及记录复灌时心律失常、复跳时间等情况,均不使用药物恢复心律。并于实验结束后取心肌组织测定丙二醛(MDA)、三磷酸腺苷(ATP)、乳酸(LD)含量。结果 DEX组心脏复跳时间明显短于I/R组(P<0.05);T_2时点I/R组有6例发生心律失常,2min内有2例恢复正常节律;DEX组有2例发生心律失常,2min内有1例恢复正常节律;与T_0时点比较,DEX组T_(1~3)时点HR降低(P<0.05),I/R组T_2~3时点HR降低(P<0.05)。与C组比较,T_(2~3)时点I/R组HR降低P<0.05),T_(1~3)时点DEX组HR降低(P<0.05);与I/R组比较,T_(1~3)时点DEX组HR降低(P<0.05);与C组比较,I/R组、DEX组心肌组织MDA、LD含量增高,心肌组织ATP含量降低(P<0.05);与I/R组比较,DEX组心肌组织MDA、LD含量降低,心肌组织ATP含量增高(P<0.05)。结论右美托咪啶可通过抑制缺血再灌注损伤心肌组织MDA、LD含量的增高及ATP的消耗,并可降低缺血再灌注后心律失常的发生,而达到保护缺血再灌注损伤心肌细胞的作用。

Objective To observe the effects of dexmedetomidine on the content of malondialdehyde（MDA）,adenosine triphosphate（ATP）,lactic acid（LD）after ischemia-reperfusion of isolated rabbit hearts and thus to explore the protective effect of dexmedetomidine on myocardial ischemia-reperfusion injury.Methods 18 healthy adult rabbits were randomly divided into 3 groups after the establishment of Langendorff isolated perfusion model and continuous K-H fluid perfusion for 15 min.In the control group（group C）,37 ℃ K-H fluid was continuously perfused and balanced for 150 min.in the ischemia/reperfusion group（group I/R）,K-H fluid was stopped after continuous perfusion for 15 min,and then the heart was stopped for 60 min via perfusion of Thomas solution（4 ℃,10mL/kg）and protected by low temperature Thomas solution（4 ℃）around the heart.The heart was stopped for 60 min via perfusion of Thomas solution（4 ℃,10mL/kg）and protected by low temperature Thomas solution（4 ℃）around the heart.Thomas solution（4 ℃,5mL/kg）was re-perfused 30 min after the first injection of Thomas solution,and the heart was perfused with K-H fluid 60 min after the first injection of Thomas solution.In dexmedetomidine given group（group DEX）,dexmedetomidine was added in the K-H fluid and the Thomas solution（25ng/mL）.The other procedures were the similar to I/R group.The heart rate（HR）were recorded at the time of balance perfusion 15min（T0）,continuous perfusion 15min/balance 30min（T1）,reperfusion 30min/balance 120 min（T2）and reperfusion 60 min/balance 150min（T3）.The arrhythmia and the time to restore normal heart rhythm without the aid of medicine at reperfusion were recorded.The levels of myocardial MDA,ATP and LD were measured at the end of the experiment.Results The restoration time of normal heart rhythm in Group DEX was significantly shorter than group I/R（P〈0.05）.In group I/R at reperfusion,6cases were found arrhythmia,and 2 cases with arrhythmia restored to normal heart rhythm within 2 minutes.In Group DEX,2 cases were found arrhythmia,and 1 case with arrhythmia restored to normal heart rhythm within 2minutes.Compared to HR at T0 point,HR in group I/R at T2 and T3 points and HR in group DEX at T1-3 were all slower（P〈0.05）.Compared to group C,HR in group I/R at T2 and T3 points and HR in group DEX at T1-3 were all slower（P〈0.05）.Compared to group I/R,HR in group at T1-3 point was lower（P〈0.05）.Compared to group C,the levels of myocardial MDA and LD in group I/R and group DEX were significantly increased,and the ATP level was significantly reduced（P〈0.05）.Compared to group I/R,the levels of myocardial MDA and LD in group DEX were significantly decreased,and the ATP level was significantly increased（P〈0.05）.Conclusion Dexmedetomidine protects the ischemia reperfusion injury of myocardial cells and reduces arrhythmia after ischemia-reperfusion by decreasing the consumption of ATP and increasing the levels of myocardial MDA and LD.