普罗帕酮和胺碘酮对起搏阈值影响的实验和临床研究
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摘要
临床观察到半数以上植入起搏器或埋藏式心脏复律除颤器的患者需要合并应用抗心律失常药物。某些抗心律失常药物可引起起搏阈值或除颤阈值升高,导致起搏功能障碍或除颤失败等严重后果。故研究常用抗心律失常药物对起搏阈值等参数的影响具有重要的临床意义。本研究观察Ⅰc类抗心律失常药物普罗帕酮和Ⅲ类抗心律失常药物胺碘酮对起搏阈值等参数的影响。临床研究部分观察了静脉常用剂量普罗帕酮和胺碘酮对起搏阈值等参数的影响;实验部分观察了逐步加大普罗帕酮和胺碘酮剂量后对起搏阈值、血流动力学和电生理学参数的影响。
方法 动物实验对象为成年杂种狗12只,雌雄不拘,重14.21±1.98Kg(13-17Kg),分为普罗帕酮组和胺碘酮组,每组6只。静脉注射戊巴比妥钠30mg/Kg麻醉,维持自主呼吸。切开颈静脉,放置心房和心室电极后测定基础心房和心室起搏阈值、P波和R波振幅、心房和心室电极阻抗,测定基础动脉血压、心率,起搏前后心电图的PR、QRS和QTc间期。每隔20分钟静脉注射普罗帕酮一次,连续5次,普罗帕酮剂量依次是3.1mg/Kg,3.1mg/Kg,4.65mg/Kg,4.65mg/Kg,6.2mg/Kg。每次用药后5分钟测定上述指标,并留取血液标本测定药物血清浓度。胺碘酮组实验方法同上,胺碘酮剂量依次是10mg/Kg,10mg/Kg,15mg/Kg,15mg/Kg,20mg/Kg。临床试验选取植入永久起搏器后3个月内的患者20例,测定基础参数后连续静脉注射2次常用剂量的普罗帕酮(70mg/次),间隔20分钟,然后分别于用药后0、30、60、90、120分钟测定上述指标。经过5个半衰期后,静脉注射2次常用剂量的胺碘酮(150mg/次),间隔20分钟,然后分别于用药后0、30、60、90、120分钟测定上述指
More than half of patients with pacemaker and implantable cardioverter-defibrillator receives antiarrhythmics in order to control tachycardia. It is known that some antiarrhythmics increase pacing threshold and cause pacing failure. Therefore, it is valuable to evaluate the effect of some common antiarrhythmics on pacing threshold and give clinicians advises regarding a possible relation between antiarrhythmic drugs and pacemakers. This study focused on the efficacy and safety of propafenone and amiodarone in dogs and patients. The clinic trial was established to observe the effect of routine dose propafenone or amiodarone on pacing threshold within 3 months after pacemaker implantation. The experiment research was set to increase the doses of propafenone or amiodarone gradually and to observe the effect of propafenone and amiodarone on the pacing threshold at larger doses.Methods: The experiment was performed in 12 adult mongrel dogs weighting 14.21±1.98Kg (13-17Kg). Under general anesthesia with intravenous barbital sodium (30mg/Kg), two electrical catheters were inserted into the right atrium and the right ventricle through jugular vein, respectively. The basic atrial and ventricular pacing threshold, sensing threshold and lead impedance, blood pressure, heart rate (HR), PR interval, QRS duration and QTc interval were obtained. Propafenone were intravenously administered in different doses (3.1mg/Kg, 3.1mg/Kg, 4.65mg/Kg, 4.65mg/Kg and 6.2mg/Kg) during a 20-minute period. After drugs, the parameters above were determined repeatedly. For the amiodarone group, the experimental procedures were same as the propafenone group and the doses were 10mg/Kg, 10mg/Kg, 15mg/Kg, 15mg/Kg, 20mg/Kg, respectively. In the clinical trial, 20 patients with permanent pacemaker received 2 intravenous doses of propafenone (70mg for
each), and the parameters above were determined following propafenone administration. These parameters were monitored at 0, 30, 60, 90, 120 minutes after drug administration. After 5 half-life time of propafenone, 2 doses (150mg for each) of amiodarone were intravenously given to the same patient. The chromatographic condition of propafenone and amiodarone with high performance liquid chromatography was established to determine serum concentrations of propafenone and amiodarone.Result: Experimental Study: With increasing of propafenone doses, mean blood pressure (MBP) and HR decreased, and PR interval, QRS duration and QTc interval prolonged gradually, and pacing threshold increased. When propafenone reached a dose of 6.2mg/Kg, MBP decreased and HR from 142±llmmHg to 67±12mmHg and 163±13 bpm to 90±10 bpm, respectively (all P<0.01), compared with the baseline. PR interval, QRS duration and QTc interval prolonged from 98±10ms to 159±28ms, 40±5ms to 102±22ms, 315±32ms to 366±18ms, respectively (all PO.01). Atrial and ventricular pacing threshold increased from 0.98±0.36V to 8.25±1.92V and 0.55±0.35V to 2.30±1.78V, respectively (all P<0.01). P or R amplitude decreased from 4.8±1.3mV to 1.6±0.7mV (P<0.01) and 20mV to 18.3±2.2mV (P<0.05), respectively.For amiodarone, MBP decreased from 134±21 to 59±21 mmHg (P<0.01) after the first dose. After administration of amiodarone, HR decreased, and PR interval, QRS duration and QTc interval prolonged gradually. Following the all 5 doses of amiodarone, HR decreased from 173±19 to 69±22bpm (P<0.01) and PR interval, QRS duration and QTc interval prolonged from 93±10ms to 134±13ms (P<0.01), 43±8ms to 90±21ms (P<0.01), 316±35ms to 322±21ms (P>0.05), respectively. Atrial or ventricular pacing threshold increased from 0.8±0.22V to 0.92±0.36V (P<0.01) and 0.40±0.12V to 0.5±0.11V (P>0.05).Clinic Trial: After drug administration, HR decreased, and PR interval,
方法 动物实验对象为成年杂种狗12只,雌雄不拘,重14.21±1.98Kg(13-17Kg),分为普罗帕酮组和胺碘酮组,每组6只。静脉注射戊巴比妥钠30mg/Kg麻醉,维持自主呼吸。切开颈静脉,放置心房和心室电极后测定基础心房和心室起搏阈值、P波和R波振幅、心房和心室电极阻抗,测定基础动脉血压、心率,起搏前后心电图的PR、QRS和QTc间期。每隔20分钟静脉注射普罗帕酮一次,连续5次,普罗帕酮剂量依次是3.1mg/Kg,3.1mg/Kg,4.65mg/Kg,4.65mg/Kg,6.2mg/Kg。每次用药后5分钟测定上述指标,并留取血液标本测定药物血清浓度。胺碘酮组实验方法同上,胺碘酮剂量依次是10mg/Kg,10mg/Kg,15mg/Kg,15mg/Kg,20mg/Kg。临床试验选取植入永久起搏器后3个月内的患者20例,测定基础参数后连续静脉注射2次常用剂量的普罗帕酮(70mg/次),间隔20分钟,然后分别于用药后0、30、60、90、120分钟测定上述指标。经过5个半衰期后,静脉注射2次常用剂量的胺碘酮(150mg/次),间隔20分钟,然后分别于用药后0、30、60、90、120分钟测定上述指
More than half of patients with pacemaker and implantable cardioverter-defibrillator receives antiarrhythmics in order to control tachycardia. It is known that some antiarrhythmics increase pacing threshold and cause pacing failure. Therefore, it is valuable to evaluate the effect of some common antiarrhythmics on pacing threshold and give clinicians advises regarding a possible relation between antiarrhythmic drugs and pacemakers. This study focused on the efficacy and safety of propafenone and amiodarone in dogs and patients. The clinic trial was established to observe the effect of routine dose propafenone or amiodarone on pacing threshold within 3 months after pacemaker implantation. The experiment research was set to increase the doses of propafenone or amiodarone gradually and to observe the effect of propafenone and amiodarone on the pacing threshold at larger doses.Methods: The experiment was performed in 12 adult mongrel dogs weighting 14.21±1.98Kg (13-17Kg). Under general anesthesia with intravenous barbital sodium (30mg/Kg), two electrical catheters were inserted into the right atrium and the right ventricle through jugular vein, respectively. The basic atrial and ventricular pacing threshold, sensing threshold and lead impedance, blood pressure, heart rate (HR), PR interval, QRS duration and QTc interval were obtained. Propafenone were intravenously administered in different doses (3.1mg/Kg, 3.1mg/Kg, 4.65mg/Kg, 4.65mg/Kg and 6.2mg/Kg) during a 20-minute period. After drugs, the parameters above were determined repeatedly. For the amiodarone group, the experimental procedures were same as the propafenone group and the doses were 10mg/Kg, 10mg/Kg, 15mg/Kg, 15mg/Kg, 20mg/Kg, respectively. In the clinical trial, 20 patients with permanent pacemaker received 2 intravenous doses of propafenone (70mg for
each), and the parameters above were determined following propafenone administration. These parameters were monitored at 0, 30, 60, 90, 120 minutes after drug administration. After 5 half-life time of propafenone, 2 doses (150mg for each) of amiodarone were intravenously given to the same patient. The chromatographic condition of propafenone and amiodarone with high performance liquid chromatography was established to determine serum concentrations of propafenone and amiodarone.Result: Experimental Study: With increasing of propafenone doses, mean blood pressure (MBP) and HR decreased, and PR interval, QRS duration and QTc interval prolonged gradually, and pacing threshold increased. When propafenone reached a dose of 6.2mg/Kg, MBP decreased and HR from 142±llmmHg to 67±12mmHg and 163±13 bpm to 90±10 bpm, respectively (all P<0.01), compared with the baseline. PR interval, QRS duration and QTc interval prolonged from 98±10ms to 159±28ms, 40±5ms to 102±22ms, 315±32ms to 366±18ms, respectively (all PO.01). Atrial and ventricular pacing threshold increased from 0.98±0.36V to 8.25±1.92V and 0.55±0.35V to 2.30±1.78V, respectively (all P<0.01). P or R amplitude decreased from 4.8±1.3mV to 1.6±0.7mV (P<0.01) and 20mV to 18.3±2.2mV (P<0.05), respectively.For amiodarone, MBP decreased from 134±21 to 59±21 mmHg (P<0.01) after the first dose. After administration of amiodarone, HR decreased, and PR interval, QRS duration and QTc interval prolonged gradually. Following the all 5 doses of amiodarone, HR decreased from 173±19 to 69±22bpm (P<0.01) and PR interval, QRS duration and QTc interval prolonged from 93±10ms to 134±13ms (P<0.01), 43±8ms to 90±21ms (P<0.01), 316±35ms to 322±21ms (P>0.05), respectively. Atrial or ventricular pacing threshold increased from 0.8±0.22V to 0.92±0.36V (P<0.01) and 0.40±0.12V to 0.5±0.11V (P>0.05).Clinic Trial: After drug administration, HR decreased, and PR interval,
引文
1. Myerburg RJ. Kesserler KM, Castellanon A. Sudden cardiac death: structure, function, and time-dependence of risk. Circulation. 1992; 85(Suppl Ⅰ): 2-10.
2. Wilber DJ, Garan H, Finklestein D, et al. Out of hospital cardiac arrest: use of electrophysiologic testing in the prediction of long term outcome. N Engl J Med. 1988; 318: 19-24.
3. Kuchar DL, Garan H, Ruskin JB. Electrophysiologic evaluation of antiarrhythmic theraphy for ventricular tachycarrhythmias. Am J Cardiol. 1989; 62: 39H-45H.
4. Preston TA, Barold SS. Problems in measuring threshold for cardiac
2. Wilber DJ, Garan H, Finklestein D, et al. Out of hospital cardiac arrest: use of electrophysiologic testing in the prediction of long term outcome. N Engl J Med. 1988; 318: 19-24.
3. Kuchar DL, Garan H, Ruskin JB. Electrophysiologic evaluation of antiarrhythmic theraphy for ventricular tachycarrhythmias. Am J Cardiol. 1989; 62: 39H-45H.
4. Preston TA, Barold SS. Problems in measuring threshold for cardiac