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目的观察2-甲硫基三磷酸腺苷(2-MeS ATP)对充血性心力衰竭(CHF)心室电生理的影响。方法 45只雄性新西兰大耳白兔分为对照组、CHF组和2-MeS ATP组。CHF组和2-MeS ATP组均行CHF模型制备。CHF模型制备是经兔耳缘静脉注射异丙肾上腺素(每天每公斤体重0.3 mg,连续注射3周)诱导。喂养6个月后。记录在体心脏左心室单相动作电位(MAP)和程控以及短阵快速刺激方法观察静息膜电位(RMP)、动作电位幅度(APA)、最大上升速率(V_(max))、复极化到20%和50%以及90%时程(APD_(20)、APD_(50)、APD_(90))以及有效不应期(ERP)和室性心律失常诱发率等指标。2-MeS ATP组于CHF免静脉滴注2-MeS ATP(10 mg/kg)20 min,然后维持静脉滴注过程中完成上述指标检测。酶解法分离各组单个心室肌细胞全细胞膜片钳技术记录心室肌细胞瞬时外向钾电流(I_(to)),以各自指令电位为横坐标,相对应的电流密度为纵坐标,绘制电流-电压(I-V)曲线。2-MeS ATP组分离单个心室肌细胞后用含有2-MeS ATP(25μmol/L)的细胞外液灌流CHF心室肌细胞10 min完成上述试验。结果最后各组均入选10只兔。与对照组比较,CHF组RMP和APA明显降低,V_(max)减慢,APD均显著延长(P均<0.05);与CHF组比较,2-MeS ATP组RMP和APA增加,V_(max)增快,各APD都显著缩短(P均<0.05)。CHF组较对照组ERP显著延长,与APD_(90)的比值严重降低,诱发室性心律失常的刺激周长(BCL)明显增加,室性心律失常的诱发率上升,持续时间更长(P均<0.01);而2-MeS ATP组较CHF组ERP明显缩短,和APD_(90)的比值显著增加,被诱发室性心律失常的BCL严重缩短,室性心律失常的诱发率和持续时间均降低(P均<0.01)。与CHF组比较,2-MeS ATP组I_(to)的电流密度增加,当钳制电位为+50 mV时,2-MeS ATP能够使I_(to)的电流密度由CHF组的(7.94±3.53)pA/pF增加到(11.79±4.51)pA/pF(P<0.01),2-MeS ATP组较CHF组心室肌细胞I_(to)的I-V曲线明显上抬,接近对照组。结论 2-MeSATP可以使CHF心肌APD缩短,室性心律失常的易感性降低,起到抗CHF后室性心律失常作用。
Objective To investigate the effects of 2-methyl-S-ATP on ventricular electrophysiology in patients with congestive heart failure (CHF). Methods 45 male New Zealand white rabbits were divided into control group, CHF group and 2-MeS ATP group. CHF group and 2-MeS ATP group were prepared CHF model. The CHF model was induced by intravenous injection of isoproterenol (0.3 mg / kg body weight per day, 3 consecutive weeks) in the rabbit ear vein. After 6 months of feeding. The ventricular membrane potential (RMP), action potential amplitude (APA) and maximal rate of increase (V max) were recorded in the left ventricular single-phase action potential (MAP) (APD_ (20), APD_ (50), APD_ (90)), 20% and 50%, as well as 90% of the time course of induced refractory period (ERP) and ventricular arrhythmia induction rate. In the 2-MeS ATP group, 2-MeS ATP (10 mg / kg) was intravenously injected into CHF for 20 min, and then the above indexes were detected during the maintenance of intravenous drip. Whole cell patch clamp technique was used to record the transient outward potassium current (I_ (t)) of ventricular myocytes in each group by enzymolysis method. The respective command potentials were abscissa and the corresponding current density was taken as the ordinate. The current-voltage (IV) curve. The above experiment was performed after perfusion of CHF ventricular myocytes with 2-MeS ATP (25 μmol / L) extracellular fluid in 2-MeS ATP group isolated from single ventricular myocytes. Results Each group was selected 10 rabbits. Compared with control group, RMP and APA in CHF group decreased significantly, Vmax decreased and APD prolonged significantly (all P <0.05). Compared with CHF group, RMP and APA in 2-MeS ATP group increased, Faster, all APD were significantly shortened (P <0.05). Compared with control group, CHF significantly prolonged in CHF group, and the ratio of APD 90 to APD 90 was significantly lower than that in control group. The BCL increased significantly and the induction rate of ventricular arrhythmia increased (P <0.01). Compared with CHF group, ERP in 2-MeS ATP group was significantly shortened and the ratio of APD_ (90) was significantly increased. BCL induced ventricular arrhythmia was severely shortened and the induction rate and duration of ventricular arrhythmias were decreased (P <0.01). Compared with CHF group, the current density of I-to in 2-MeS ATP group increased. When the clamp potential was +50 mV, the current density of I-to-current was decreased from (7.94 ± 3.53) pA / pF increased to (11.79 ± 4.51) pA / pF (P <0.01). The IV curve of ventricular myocytes in 2-MeS ATP group was significantly higher than that in CHF group, which was close to the control group. Conclusions 2-MeSATP can shorten the myocardial APD of CHF and decrease the susceptibility of ventricular arrhythmia, and play the role of anti-CHF ventricular arrhythmia.