右美托咪定对家兔离体心脏缺血-再灌注时心肌单相动作电位及跨室壁复极离散度的影响

目的观察右美托咪定对家兔离体心脏缺血-再灌注心肌动作电位及跨室壁复极离散度的影响,探讨其对缺血-再灌注心肌电生理特性的作用。方法健康成年家兔18只,体重(2.0±0.5)kg,成功制备Langendorff离体心脏灌注模型,K-H液平衡灌注15min后,随机分为三组,每组6只:空白对照组(C组):持续平衡灌注37℃K-H液150min;缺血-再灌注组(IR组):K-H液继续灌注15min后停止,注射Thomas液(4℃,10 ml/kg)使心脏停搏60 min,心脏周围用低温(4℃)Thomas液保护,30min半量复灌Thomas液(4℃,5ml/kg),60min时复灌K-H液;右美托咪定组(DEX组):于K-H液及Thomas液中加入右美托咪定(25ng/ml),余同IR组。记录平衡灌注15min(T0)、继续灌注15min/平衡30min(T1)、复灌30min/平衡120min(T2)、复灌60min/平衡150min(T3)的HR及三层心肌内膜(Endo)、中膜(Mid)、外膜(Epi)]单相动作电位振幅(monophonic action potential amplitude,MAPA),0相最大上升速率(Vmax),90%单相动作电位时程(monophonic action potential duration,MAPD90)并计算跨室壁复极离散度(transmural dispersion of repolarization,TDR),观察心脏复灌时心律失常、复跳时间,均不使用药物恢复心律。结果 DEX组心脏复跳时间(16.67±3.78)s明显短于IR组(46.33±7.29)s(P0.05);心脏复跳时IR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T0时比较,T2、T3时IR组,T1~T3时DEX组HR明显减慢(P0.05);与T1时比较,T2、T3时DEX组HR明显减慢(P0.05);与T2时和C组比较,T3时DEX组HR明显减慢(P0.05);T1~T3时DEX组HR明显慢于IR组(P0.05)。与T0时比较,T1时DEX组Mid部位,T2、T3时DEX组Epi、Mid、Endo部位的MAPD90明显延长(P0.05)。与T1时比较,T3时DEX组Epi、Mid、Endo部位的MAPD90明显延长(P0.05);T3时DEX组Mid部位的MAPD90明显长于C组(P0.05);T2、T3时DEX组Epi、Mid、Endo部位的MAPD90明显长于IR组(P0.05)。与T0时和C组比较,T2、T3时IR组,T1~T3时DEX组TDR明显增大(P0.05);T2、T3时DEX组TDR明显小于IR组(P0.05)。结论右美托咪定能够延长MAPD、抑制缺血-再灌注损伤后心肌复极不均一性,具有稳定缺血-再灌注心肌电生理特性的作用。

Effects of dexmedetomidine on the monophasic action potential duration and transmural dispersion of re-polarization during ischemia-reperfusion in isolated rabbit hearts

Objective To study the effects of dexmedetomidine on the monophasic action po-tential duration and the transmural dispersion of repolarization during ischemia-reperfusion of isolated rabbit hearts and thus explore its effect on myocardial ischemia-reperfusion electrophysiological char-acteristics.Methods Eighteen healthy adult rabbits,weighing (2.0±0.5)kg,were randomly divided into 3 groups after successful preparation of Langendorff isolated heart perfusion model and 1 5 min perfusion and balance of K-H fluid.In the control group (group C),37 ℃ K-H fluid was continuously perfused and balanced for 1 50 min.In the ischemia/reperfusion group (group IR),K-H fluid was stopped after continuous perfusion and balance for 1 5 min and cardiac arrest was induced for 60 min with the injection of Thomas solution (4 ℃,10 ml/kg)while the heart was protected by the low tem-perature Thomas solution (4 ℃)around it.Reperfusion of Thomas solution (4 ℃,5 ml/kg)was performed for 30 min and the heart was resuscitated by the perfusion of K-H fluid for 60 min.In dexmedetomidine group (group DEX),dexmedetomidine (25 ng/ml)was added in the K-H fluid and the Thomas solution.Other procedures were same as in group IR.Heart rate(HR),monophasic ac-tion potential amplitude (MAPA)of the three layers of heart endocardium (Endo),myocardium (Mid)and epicardium (Epi)],0 phase maximal increase rate (Vmax),90% monophasic action po-tential duration (MAPD90 )and transmural dispersion of repolarization (TDR)were recorded at the time of continuous balance perfusion 1 5 min(T0 ),continuous perfusion 1 5 min/balance 30 min(T1 ), reperfusion 30 min/balance 120 min(T2 )and reperfusion 60 min/balance 1 50 min(T3 ).Cardiac ar-rhythmia and resuscitation time at cardiac reperfusion were observed,without using drugs to restore normal cardiac rhythm.Results In group DEX,cardiac resuscitation time was significantly shorter (1 6.67±3.78)s than that in group IR (46.33±7.29)s (P <0.05);At T2 ,in group IR,arrhythmia was seen in 6 rabbits and normal cardiac rhythm was restored within 2 min in two rabbits,while in group DEX,arrhythmia was seen in 2 rabbits and normal cardiac rhythm was restored within 2 min in one rabbit,without the use of any drugs.When compared with T0 ,HR was slower at T2 and T3 in group IR and at T1-T3 in group DEX (P <0.05);Compared with T1 ,HR was slower at T2 and T3 in group DEX (P <0.05);Compared with T2 and group C,HR was slower at T3 in group DEX;At T1-T3 ,HR in group DEX were significantly slower than that in group IR (P <0.05).Compared with T0 ,MAPD90 of Mid at T1 and Epi,Mid,Endo at T2 and T3 in group DEX were significantly extend-ed (P <0.05);Compared with T1 ,MAPD90 of Epi,Mid,Endo in group DEX were significantly ex-tended at T3 ;MAPD90 of Mid in group DEX was significantly longer than that in group C at T3 (P <0.05);At T2 and T3 ,MAPD90 of Epi,Mid,Endo in group DEX were longer than that in group IR (P <0.05).Compared with T0 and group C,TDR at T2 and T3 in group IR and at T1-T3 in group DEX significantly increased (P <0.05),while TDR in group DEX were less than that in group IR at T2 and T3 (P <0.05).Conclusion Dexmedetomidine appeared to prolong MAPD and restrain the dis-proportion of resuscitation of myocardial ischemia-reperfusion injury.Dexmedetomidine could have the effect of stabilizing myocardial ischemia-reperfusion electrophysiological characteristics.