RESUMEN
Aim To investigate the inhibitory effects of zacopride(Zac) on arrhythmia induced by isoproterenol ( ISO) and the underlying mechanisms in rats. Meth-ods ①ECGs were recorded in anesthetized rats in vi-vo to observe the effects of zacopride on arrhythmia in-duced by ISO. ② Intracellular microelectrode tech-nique was used to investigate the effects of zacopride on resting membrane potential, delayed afterdepolariza-tions ( DADs) and triggered activity ( TA) induced by ISO combined with 3. 6 mmol·L-1 CaCl2 in right ven-tricular papillary muscle of rats. Results ① In ISO group rats, ventricular premature beats ( VPB ) oc-curred frequently with ST-segment depression. Com-pared with ISO group, the incidence of VPB in ISO+Zac group decreased from 100% to 50% ( n=6 , P<0. 05 ) and the total number of VPB recorded in 1 hour significantly reduced from 1 574 ± 521 to 33 ± 40 ( n=6,P<0. 05). ② Zacopride at 1 μmol·L-1 could hy-perpolarize the resting membrane potential of right ven-tricular papillary muscle in normal rat from ( -74. 42 ± 1. 95 ) mV to ( -78. 50 ± 2. 07 ) mV ( n =6 , P <0. 05). ③ Zacopride at 1 μmol·L-1 significantly de-pressed the DADs and TA induced by ISO combined with 3. 6 mmol·L-1 CaCl2 in right ventricular papilla-ry muscle. The incidence of DADs decreased from 93. 75% in rats in ISO group to 25% in ISO +Zac group ( n =16 , P <0. 05 ) , and this antiarrhythmic effect could be reversed by 1 μmol·L-1 BaCl2 . Conclusions Zacopride, a selective IK1 channel ago-nist , can significantly inhibit cardiac arrthymia induced by ISO in rats, the mechanism of which is mainly at-tributed to zacopride-induced hyperpolarization of the resting membrane potential and subsequent suppression of DADs and TA via enhancing IK1 . These results pro-vide further evidence that to enhance IK1 moderately may be a feasible pathway for antiarrthymic therapy.
RESUMEN
Objective To study the influence of high dose atorvastatin (80 mg/d) in early heart rate variability and malignant ventricular arrhythmia in patients underwent emergency coronary intervention (PCI). Methods A total of 350 pa-tients underwent emergency PCI were randomly divided into two groups:high dose atorvastatin group and regular dose atorv-astatin group. And 85 cases of control were enrolled randomly. The patients using high dose atorvastatin group received atorv-astatin 80 mg orally STAT upon hospitalization and 40 mg once a day from the second day. The patients using regular dose atorvastatin group received atorvastatin 40 mg orally STAT after hospitalization and 20 mg once a day from the second day. Patients were monitored by continuous dynamic electrocardiogram for 24 hours after PCI. According to the results of dynamic electrocardiogram, the early heart rate variability (HRV) and rate of malignant ventricular arrhythmia (MVA) were measured and compared between three groups. Results The values of standard deviation of all normal sinus RR intervals over 24 h (SDNN) were(108.3 ± 21.5)ms and(70.6 ± 17.6)ms for high dose atorvastatin group and regular dose atorvastatin group re-spectively. The values of SDNN measured every 5 minutes during 24 hours (SDANN) were (111.7 ± 19.2)ms and (65.9 ± 18.5)ms respectively, and values of root-mean-square of successive normal sinus RR interval difference (RMSSD) were (25.6±8.3)ms and(18.7±10.2)ms respectively, and the percentage of adjacent RR intervals that differed by more than 50 ms (PNN50) were(14.7±5.9)%and(6.9±3.4)%for high dose atorvastatin group and regular dose atorvastatin group respec-tively. The above data were significantly lower than those in control group [ (122.5±23.8) ms and (119.6±15.2) ms, (29.2±9.3) ms and (17.7±6.5)%, P＜0.05]. There were significantly higher values in high dose atorvastatin group than those in regular dose atorvastatin group (P＜0.05). The incidence rate of MVA was much higher in high dose atorvastatin group and regular dose atorvastatin group than that in normal control group (12.00%vs 21.14%vs 2.35%). The incidence rate of MVA was sig-nificantly lower in high dose atorvastatin group than that in regular dose atorvastatin group (χ2=5.29, P＜0.05). Conclu-sion The HRV was significantly reduced and the incidence rate of MVA was much higher in patients with early AMI. High-dose atorvastatin can increase the HRV and decrease the incidence rate of MVA in patients underwent emergency PCI.