氟哌啶醇对心脏电生理学影响的实验研究
摘要
研究的目的：
1．采用在体兔心脏模型研究氟哌啶醇(Haloperidol，Hal)对兔动脉血压和心脏电生理参数的影响。
2．采用Langendorff离体灌注兔心脏模型，排除神经、体液因素的影响，研究氟哌啶醇对离体兔心脏电生理参数的影响。
3．采用多种实验性心律失常模型研究氟哌啶醇对实验性心律失常的影响。
研究的材料和方法：
1．氟哌啶醇对在体兔心脏电生理参数的影响。大耳白兔用3％戊巴比妥钠30mg·kg~(-1)经耳缘静脉麻醉；经左颈总动脉插管至升主动脉，测定动脉血压；经右侧颈外静脉插入一根5F的4极Cordis电极导管至右心房内；胸骨左缘开胸，保持自主呼吸，维持窦性心律，将自制四极心肌插入电极插入左心耳右下缘室间沟左室侧的心室壁内。四极电极的第3～4极为刺激电极，连接SEC-2102型刺激器，第1～2极为记录电极，将生物电信号输入RM-6000型多导生理仪和FC-14型磁带记录仪，通过它们示波观察并记录资料。皮下针状电极刺入白兔四肢，连接ECG-6511型心电图机，记录肢体导联体表心电图。各组在用药前10min，静脉注入生理盐水10ml或氟哌啶醇1.0mg·kg~(-1)或2.0mg·kg~(-1)后10、30和60min，分别测定动脉收缩压(systolic arterial blood pressure，SABP)、动脉舒张压(diastolic arterial blood pressure，DABP)和平均动脉压(mean arterial blood pressure，MABP)；心房舒张期阈值(atrial diastolic threshold，ADT)、心房相对不应期(atrial relative refractory period，ARRP)、心房有效不应期(atrial effective refractory period，AERP)、心室舒张期阈值(ventricular diastolic threshold，VDT)、心室相对不应期(ventricular relative refractory period，VRRP)、心室有效不应期(ventricular effectivere fractory period，VERP)；心率(heart rate，HR)、窦房传导时间(sinoatrial conduction time，SACT)、窦房结恢复时间(sinoatrial
node recovery time，S皿）、房室传导的文氏点（Wenckebach’s cycle length，
WCL）和2：1阻滞点（2：lblOCkillgpoiflt，2：IB）。
2．氟听咤醇对离体兔心脏电生理参数的影响。
采用Langendorff离体兔心脏灌注模型，分别将两根自制四极心肌插
入电极插入右心耳心房壁及左心耳右下缘室间沟左室侧心室壁内，将第
3～4极作为刺激电极，连接 SEC—ZI 02型刺激器，第 l～2极作为记录
电极，将生物电信号输入 llA6000型多导生理仪和 FCJ 型磁带记录仪，
通过它们示波观察并记录资料。各组在用Krebs－Henseleit（K－H）灌注液灌
注 10min时、用含氟if＄＠醇浓度为 0刀0 u mol·L’或 0尸5 u mol·L”‘或
1．50 p md·LJ的K－H灌注液灌注兔心脏m、25和45 min，分别测定
ADT、ARRP、AERP、VDT、VRRP、VERP、HR、SACT、SNRT。
3．氟呢陡醇对实验性心律失常的影响。
采用氯仿、氯化钙、氯仿－肾上腺素、西地兰和电刺激致心律失常模
型研究氟呢咳醇对心律失常的影响。小鼠吸入氯仿直至呼吸停止，立即
剖胸观察室颤的发生率；Wstar大鼠用乌拉坦 1．Zg止g”’腹腔麻醉后经静
脉注射 3．5％氯化钙 140mg·kg“’诱发室颤，观察室颤的发生率；大耳白
兔用氯仿吸入麻醉后，经耳缘静脉快速注入0刀1％的肾上腺素50fig人g“’
诱发心律夫常，观察心律夫常的持续时间；豚鼠用乌拉坦 1．Zg·kg”‘腹腔
注射麻醉后，用PFA－型输液泵经静脉恒速输入0刀2％。西地兰6fig·min－’，
分别记录导致豚鼠室性早搏巾entricular extrasystole，VE卜室性心动过速
（ventrlcula tachycardla，Vn、心室颤动。，entricular ibrillation，Vn和心跳
停止仁盯山砒。rest，＊川时西地兰的用量：大耳白兔用3％戊巴比妥钠
3 omg·kg’‘麻醉后开胸，左心室壁插入四极电极，用脉冲串刺激诱发室
颤，观察诱发室颤的致颤阈值。用统计学方法比较用药组和对照组之间
存在的差异。
研究的结果：
1．氟腑陡醇对在体兔心脏电生理参数的影响。
和对照组相比较，Hal刀 mg组和 Hal刀 mg组在用药后 10、3 0、
60m5n，S ABABP、＊AB P、MAB P均显著下降（P＜0＊1）。AD T、＊＊T显著提
2
高o＜0＊5，P0＊1），A．－．－e－、AE RP、＊RRP、VE RP显著延长①＜0＊5，
P＜0＊1）。IDI显著减慢o＜0＊5，P＜0＊1），S＊＊T、S NRTNRT、＊＊L、2：IB
显著延长瞩＜0刀 1卜和 Hal刀 mg组相比较，Hal刀 mg组在用药后 10、
3o、6omln，S ABABP、＊AB P、MAB P有进一步下降O＜0＊5，P＜0＊1），AD T、
Objective:
The article aims:
1. To study the effects of haloperidol(Hal) on electrophysiologic parameters in vivo rabbit heart.
2. To study the effects of haloperidol on electrophysiologic parameters in isolated rabbit heart, eliminating action of nerves and body fluid by using standard Langendorff technique.
3. To study the effects of haloperidol on experimental arrhythmias by using various models of experimental arrhythmia.
Material and method:
1. The effects of haloperidol on electrophysiologic parameters in vivo rabbit
heart.
The rabbit was anaesthetized with 3% sodium pentobarbital(30mg 'kg'1) by intravenous infusion. The arterial pressures were monitored with a catheter put into the ascending aorta through left common carotid artery. One 5F Cordis electrode catheter of four electrodes was inserted into right atrium through the right external jugular vein. The thorax was opened via thoracotomy along the left edge of the sternum. Maintain autonomous breathing and sinus rhythm. A ventricular plunge electrode of four electrodes was inserted into the left ventricle under the left auricle and beside the anterior interventricular sulcus. The third electrode and the fourth electrode were connected with SEC-2102 model stimulator. The first electrode and the second electrode were linked to RM-6000 model polygraph physiological recorder and FC-14 model tape recorder. The ECG-6511 model electrocardiogram recorder was connected with the needle electrodes pierced into the extremities of rabbit to record the limb lead electrocardiogram. In ev
ery group, at lOmin pre-drug and at 10, 30, and 60min after NSlOml or
haloperidol l.Omg ?kg' or 2.0mg ?kg" iv, the effects of haloperidol on arterial blood pressure and cardiac electrophysiologic parameters were determined respectively, which were systolic arterial blood pressure(SABP), diastolic arterial blood pressure(DABP), mean arterial blood pressure(MABP), atrial diastolic threshold(ADT), atrial relative refractory period(ARRP), atrial effective refractory period(AERP), ventricular diastolic threshold(VDT), ventricular relative refractory period (VRRP), ventricular effective refractory period (VERP), heart rate(HR), sinoatrial conduction time(SACT), sinoatrial node recovery time(SNRT), Wenckebach's cycle length(WCL) and 2:1 blocking point(2:lB).
2. The effects of haloperidol on electrophysiologic parameters in isolated perfused rabbit heart.
In the isolated rabbit heart perfused by using standard Langendorff technique, two plunged electrode of four electrode were respectively inserted into the right atrium and the left ventricle under the left auricle and beside the anterior interventricular sulcus. The third electrode and the fourth electrode were connected with SEC-2102 model stimulator. The first electrode and the second electrode were linked to RM-6000 model polygraph physiological recorder and FC-14 model tape recorder. In every group, at lOmin perfused by Krebs-Henseleit(K-H) perfusion liquid and at 10, 25 and 45min perfused by K-H perfusion liquid with haloperidol O.OOumol ?L"1 or 0.75u.mol ?L"1 or l.SOumol ?L"1, the effects of haloperidol on its electrophysiologic parameters were observed respectively, which were ADT, ARRP, AERP, VDT, VRRP,VERP, HR, SACT, SNRT.
3. The effects of haloperidol on experimental arrhythmias.
The effects of haloperidol on experimental arrhythmias induced by chloroform, Cacl2, chloroform-adrenaline, cedilanid and electrical stimulation in various animals were observed. The mice hearts were exposed immediately via thoracotomy when their respirations were inhibited by inbreathing
chloroform and the incidences of ventricular fibrillation were observed. After anaesthetized by urethan(1.2g ?kg"1, ip), ventricular fibrillations were induced in Wistar rats with 3.5%Cacl2(140mg ?kg"1) by intravenous infusion and the incidences of ventricular fibrillation were observed. Arrhythmias were induced with 0.01% adrenaline(50ug ?kg"1) by intravenous infusion in rabbits anaesthetized by inhalation of chlorof
1．采用在体兔心脏模型研究氟哌啶醇(Haloperidol，Hal)对兔动脉血压和心脏电生理参数的影响。
2．采用Langendorff离体灌注兔心脏模型，排除神经、体液因素的影响，研究氟哌啶醇对离体兔心脏电生理参数的影响。
3．采用多种实验性心律失常模型研究氟哌啶醇对实验性心律失常的影响。
研究的材料和方法：
1．氟哌啶醇对在体兔心脏电生理参数的影响。大耳白兔用3％戊巴比妥钠30mg·kg~(-1)经耳缘静脉麻醉；经左颈总动脉插管至升主动脉，测定动脉血压；经右侧颈外静脉插入一根5F的4极Cordis电极导管至右心房内；胸骨左缘开胸，保持自主呼吸，维持窦性心律，将自制四极心肌插入电极插入左心耳右下缘室间沟左室侧的心室壁内。四极电极的第3～4极为刺激电极，连接SEC-2102型刺激器，第1～2极为记录电极，将生物电信号输入RM-6000型多导生理仪和FC-14型磁带记录仪，通过它们示波观察并记录资料。皮下针状电极刺入白兔四肢，连接ECG-6511型心电图机，记录肢体导联体表心电图。各组在用药前10min，静脉注入生理盐水10ml或氟哌啶醇1.0mg·kg~(-1)或2.0mg·kg~(-1)后10、30和60min，分别测定动脉收缩压(systolic arterial blood pressure，SABP)、动脉舒张压(diastolic arterial blood pressure，DABP)和平均动脉压(mean arterial blood pressure，MABP)；心房舒张期阈值(atrial diastolic threshold，ADT)、心房相对不应期(atrial relative refractory period，ARRP)、心房有效不应期(atrial effective refractory period，AERP)、心室舒张期阈值(ventricular diastolic threshold，VDT)、心室相对不应期(ventricular relative refractory period，VRRP)、心室有效不应期(ventricular effectivere fractory period，VERP)；心率(heart rate，HR)、窦房传导时间(sinoatrial conduction time，SACT)、窦房结恢复时间(sinoatrial
node recovery time，S皿）、房室传导的文氏点（Wenckebach’s cycle length，
WCL）和2：1阻滞点（2：lblOCkillgpoiflt，2：IB）。
2．氟听咤醇对离体兔心脏电生理参数的影响。
采用Langendorff离体兔心脏灌注模型，分别将两根自制四极心肌插
入电极插入右心耳心房壁及左心耳右下缘室间沟左室侧心室壁内，将第
3～4极作为刺激电极，连接 SEC—ZI 02型刺激器，第 l～2极作为记录
电极，将生物电信号输入 llA6000型多导生理仪和 FCJ 型磁带记录仪，
通过它们示波观察并记录资料。各组在用Krebs－Henseleit（K－H）灌注液灌
注 10min时、用含氟if＄＠醇浓度为 0刀0 u mol·L’或 0尸5 u mol·L”‘或
1．50 p md·LJ的K－H灌注液灌注兔心脏m、25和45 min，分别测定
ADT、ARRP、AERP、VDT、VRRP、VERP、HR、SACT、SNRT。
3．氟呢陡醇对实验性心律失常的影响。
采用氯仿、氯化钙、氯仿－肾上腺素、西地兰和电刺激致心律失常模
型研究氟呢咳醇对心律失常的影响。小鼠吸入氯仿直至呼吸停止，立即
剖胸观察室颤的发生率；Wstar大鼠用乌拉坦 1．Zg止g”’腹腔麻醉后经静
脉注射 3．5％氯化钙 140mg·kg“’诱发室颤，观察室颤的发生率；大耳白
兔用氯仿吸入麻醉后，经耳缘静脉快速注入0刀1％的肾上腺素50fig人g“’
诱发心律夫常，观察心律夫常的持续时间；豚鼠用乌拉坦 1．Zg·kg”‘腹腔
注射麻醉后，用PFA－型输液泵经静脉恒速输入0刀2％。西地兰6fig·min－’，
分别记录导致豚鼠室性早搏巾entricular extrasystole，VE卜室性心动过速
（ventrlcula tachycardla，Vn、心室颤动。，entricular ibrillation，Vn和心跳
停止仁盯山砒。rest，＊川时西地兰的用量：大耳白兔用3％戊巴比妥钠
3 omg·kg’‘麻醉后开胸，左心室壁插入四极电极，用脉冲串刺激诱发室
颤，观察诱发室颤的致颤阈值。用统计学方法比较用药组和对照组之间
存在的差异。
研究的结果：
1．氟腑陡醇对在体兔心脏电生理参数的影响。
和对照组相比较，Hal刀 mg组和 Hal刀 mg组在用药后 10、3 0、
60m5n，S ABABP、＊AB P、MAB P均显著下降（P＜0＊1）。AD T、＊＊T显著提
2
高o＜0＊5，P0＊1），A．－．－e－、AE RP、＊RRP、VE RP显著延长①＜0＊5，
P＜0＊1）。IDI显著减慢o＜0＊5，P＜0＊1），S＊＊T、S NRTNRT、＊＊L、2：IB
显著延长瞩＜0刀 1卜和 Hal刀 mg组相比较，Hal刀 mg组在用药后 10、
3o、6omln，S ABABP、＊AB P、MAB P有进一步下降O＜0＊5，P＜0＊1），AD T、
Objective:
The article aims:
1. To study the effects of haloperidol(Hal) on electrophysiologic parameters in vivo rabbit heart.
2. To study the effects of haloperidol on electrophysiologic parameters in isolated rabbit heart, eliminating action of nerves and body fluid by using standard Langendorff technique.
3. To study the effects of haloperidol on experimental arrhythmias by using various models of experimental arrhythmia.
Material and method:
1. The effects of haloperidol on electrophysiologic parameters in vivo rabbit
heart.
The rabbit was anaesthetized with 3% sodium pentobarbital(30mg 'kg'1) by intravenous infusion. The arterial pressures were monitored with a catheter put into the ascending aorta through left common carotid artery. One 5F Cordis electrode catheter of four electrodes was inserted into right atrium through the right external jugular vein. The thorax was opened via thoracotomy along the left edge of the sternum. Maintain autonomous breathing and sinus rhythm. A ventricular plunge electrode of four electrodes was inserted into the left ventricle under the left auricle and beside the anterior interventricular sulcus. The third electrode and the fourth electrode were connected with SEC-2102 model stimulator. The first electrode and the second electrode were linked to RM-6000 model polygraph physiological recorder and FC-14 model tape recorder. The ECG-6511 model electrocardiogram recorder was connected with the needle electrodes pierced into the extremities of rabbit to record the limb lead electrocardiogram. In ev
ery group, at lOmin pre-drug and at 10, 30, and 60min after NSlOml or
haloperidol l.Omg ?kg' or 2.0mg ?kg" iv, the effects of haloperidol on arterial blood pressure and cardiac electrophysiologic parameters were determined respectively, which were systolic arterial blood pressure(SABP), diastolic arterial blood pressure(DABP), mean arterial blood pressure(MABP), atrial diastolic threshold(ADT), atrial relative refractory period(ARRP), atrial effective refractory period(AERP), ventricular diastolic threshold(VDT), ventricular relative refractory period (VRRP), ventricular effective refractory period (VERP), heart rate(HR), sinoatrial conduction time(SACT), sinoatrial node recovery time(SNRT), Wenckebach's cycle length(WCL) and 2:1 blocking point(2:lB).
2. The effects of haloperidol on electrophysiologic parameters in isolated perfused rabbit heart.
In the isolated rabbit heart perfused by using standard Langendorff technique, two plunged electrode of four electrode were respectively inserted into the right atrium and the left ventricle under the left auricle and beside the anterior interventricular sulcus. The third electrode and the fourth electrode were connected with SEC-2102 model stimulator. The first electrode and the second electrode were linked to RM-6000 model polygraph physiological recorder and FC-14 model tape recorder. In every group, at lOmin perfused by Krebs-Henseleit(K-H) perfusion liquid and at 10, 25 and 45min perfused by K-H perfusion liquid with haloperidol O.OOumol ?L"1 or 0.75u.mol ?L"1 or l.SOumol ?L"1, the effects of haloperidol on its electrophysiologic parameters were observed respectively, which were ADT, ARRP, AERP, VDT, VRRP,VERP, HR, SACT, SNRT.
3. The effects of haloperidol on experimental arrhythmias.
The effects of haloperidol on experimental arrhythmias induced by chloroform, Cacl2, chloroform-adrenaline, cedilanid and electrical stimulation in various animals were observed. The mice hearts were exposed immediately via thoracotomy when their respirations were inhibited by inbreathing
chloroform and the incidences of ventricular fibrillation were observed. After anaesthetized by urethan(1.2g ?kg"1, ip), ventricular fibrillations were induced in Wistar rats with 3.5%Cacl2(140mg ?kg"1) by intravenous infusion and the incidences of ventricular fibrillation were observed. Arrhythmias were induced with 0.01% adrenaline(50ug ?kg"1) by intravenous infusion in rabbits anaesthetized by inhalation of chlorof
引文
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24．石刚刚，马希贤，陈锦香等．氟哌啶醇对猪冠状动脉螺旋肌条作用的研究．中国药学杂志，1996，31(3)：142-144．
25．石刚刚，魏东升，许绍芬．阿片受体激动剂对猪冠状动脉肌条作用的研究．生理学报，1994，46(2)：176-180．
26．石刚刚，许绍芬．苯环利定对离体豚鼠心脏冠状动脉流量的影响．上海医科大学学报，1994，21(2)：93-96．
27．石刚刚，郑锦鸿，陈少刚．氟哌啶醇治疗不稳定性心绞痛5例分析．汕头大学医学院学报，1997，10(2)：33-34．
28. Satoh Y, Sugiyama A, Tamura K et al. Effect of magnesium sulfate on the haloperidol-induced QT prolongation assessed in the canine in vivo model under the monitoring of monophasic action potential. Jpn Circ J, 2000, 64(6): 445-51.
29. Kobayashi T, Ikeda K, Kumanishi T. Inhibition by various antipsychotic drugs of the G-protein-activated inwardly rectifying K(+) (GIRK) channels expressed in xenopus oocytes. Br J Pharmacol, 2000, 129(8): 1716-22.
30. Suessbrich H, Schonherr R, Heinemann SH, Attali B, Lang F, Busch AE. The inhibitory effect of the antipsychotic drug haloperidol on HERG potassium channels expressed in Xenopus oocytes. Br J Pharmacol, 1997, 120(5): 968-74.
31. Nakazawa K, Ito K, Koizumi S et al. Characterization of inhibition by haloperidol and chlorpromazine of a voltage-activated K+ current in rat phaeochromocytoma cells. Br J Pharmacol, 1995, 116(6): 2603-10.
32. Drici MD, Wang WX, Liu XK et al. Prolongation of QT interval in isolated feline hearts by antipsychotic drugs. J Clin Psychopharmacol, 1998, 18(6): 477-81.
33. Tisdale JE, Kambe JC, Chow MS et al. The effect of haloperidol on ventricular fibrillation threshold in pigs. Pharmacol Toxicol, 1991, 69(5): 327-9.
34. Ogata N, Narahashi T. Block of sodium channels by psychotropic drugs in single guinea-pig cardiac myocytes. Br J Pharmacol, 1989, 97(3): 905-13.
35. Ito K, Nakazawa K, Koizumi S et al. Inhibition by antipsychotic drugs of L-type Ca2+ channel current in PC12 cells. Eur J Pharmacol, 1996, 314(1-2): 143-50.
36. Fletcher EJ, Church J, MacDonald JF. Haloperidol blocks voltage-activated Ca2+ channels in hippocampal neurones. Eur J Pharmacol, 1994, 267(2): 249-52.
37．邱汉婴，李迪俊，毛焕元等．八厘麻毒素对兔心室不应期的影响．中国药理学通报，1997，13(3)：247-248．
38．邱汉婴，魏太星，张延荣等．雷尼替丁对兔正常心室和缺血心室不应期及室颤阈值的影响．中国药理学报，1993，14(3)：260-262．
39．孙安盛，张炜，刘国雄．异钩藤碱对麻醉兔心脏传导功能的影响．中国药理学与毒理学杂志，1995，9(2)：113-115．
40．张澍，陈明哲，郭静萱等．心脏电生理检查的基本方法．见：陈明哲主编．心脏病学(第一版)．北京：北京医科大学出版社，1999，392-401．
41．邱汉婴，王海鱼，李迪俊等．八厘麻毒素对离体灌注兔心脏电生理参数的影响．中国药理学通报，2000，16(1)：75-77．
42．马传庚，张宝恒．抗心律失常药实验法．见：徐叔云，卞如濂，陈修主编．药理实验方法学(第二版)．北京：人民卫生出版社，1991，1013-1021．
43. Cuffi ML, Vila E, Badia A. Effects of some antipsychotic drugs on cardiovascular catecholamine receptors in the rat. J Auton Pharmacol, 1989, 9(6): 397-409.
44. Magliozzi JR, Hollister LE. Elimination half-life and bioavailability of haloperidol in schizophrenic patients. J Clin Psychiatry, 1985, 46(1): 20-1.
45. Cheng YF, Paalzow LK, Bondesson U et al. Pharmacokinetics of haloperidol in psychotic patients. Psychopharmacology Berl, 1987, 91(4): 410-4.
46．张鸿燕，舒良，周东丰等．氟哌啶醇的药代动力学研究．中华神经精神科杂志，1995，28(6)：325-327．
47. Kudo S, Odomi M. Involvement of human cytochrome P450 3A4 in reduced haloperidol oxidation. Eur J Clin Pharmacol, 1998, 54(3): 253-9.
48. Iwahashi K, Nakamura K, Miyatake R et al. Cardiac effects of haloperidol and carbamazepine treatment. Am J Psychiatry, 1996, 153(1): 135.
49． Takeda M, Nishinuma K, Yamashita S et al. Serum haloperidol levels of schizophrenics receiving treatment for tuberculosis. Clin Neuropharmacol, 1986, 9(4) : 386-97
50． Kudo S, Ishizaki T. Pharmacokinetics of haloperidol: an update. Clin Pharmacokinet, 1999, 37(6) : 435-56．
51． Perrault LP, Denault AY, Carrier M et al. Torsades de pointes secondary to intravenous haloperidol after coronary bypass grafting surgery. Can J Anaesth, 2000, 47(3) : 251-4．
52． Douglas PH, Block PC. Corrected QT interval prolongation associated with intravenous haloperidol in acute coronary syndromes. Catheter Cardiovasc Interv, 2000, 50(3) : 352-5．
53． Di-Salvo TG, O'Gara PT. Torsade de pointes caused by high-dose intravenous haloperidol in cardiac patients. Clin Cardiol, 1995, 18(5) : 285-90．
54． Drici MD, Barhanin J. Cardiac K+ channels and drug-acquired long QT syndrome. Therapie, 2000, 55(1) : 185-93．
55． Aunsholt NA. Prolonged Q-T interval and hypokalemia caused by haloperidol. Acta Psychiatr Scand, 1989, 79(5) : 411-412．
2. Kaneko S, Edwards JG, Goldie A et al. Effect of haloperidol decanoate on the cardiovascular system. Jpn J Psychiatry Neurol, 1991, 45(1): 73-7.
3. Tesar GE, Murray GB, Cassem NH. Use of high-dose intravenous haloperidol in the treatment of agitated cardiac patients. J Clin Psychopharmacol, 1985, 5(6): 344-7.
4. Sanders KM, Murray GB, Cassem NH. High-dose intravenous haloperidol for agitated delirium in a cardiac patient on intra-aortic balloon pump. J Clin Psychopharmacol, 1991, 11(2): 146-7.
5. Ishida H, Hoshiai K, Hoshiai M et al. Haloperidol prolongs diastolic phase of Ca(2+) transient in cardiac myocytes. Jpn J Physiol, 1999, 49(6): 479-84.
6. Riker RR, Fraser GL, Cox PM. Continuous infusion of haloperidol controls agitation in critically ill patients. Crit Care Med, 1994, 22(3): 433-40.
7. Seneff MG, Mathews RA. Use of haloperidol infusions to control delirium in critically ill adults. Ann Pharmacother, 1995, 29(7-8): 690-3.
8. Tesar GE, Stern TA. Rapid tranquilization of the agitated intensive care unit patient. J Intensive Care Med, 1988, 3(1): 195-201.
9. Franco-Bronson K, Gajwani P. Hypotension associated with intravenous haloperidol and imipenem. J Clin Psychopharmacol, 1999, 19(5): 480-1.
10．陈荣民，陈婕璇．氟哌啶醇致休克2例报告．福建医药杂志，1999，21(5)：127-128．
11．朱成友，任佃宝．高低剂量氟哌啶醇治疗精神病致心电图异常对照分析．江苏实用心电学杂志，2000，9(1)：52-53．
12．赵幸福，秦鸿霞，杨秀双．氟哌啶醇致心动过缓6例．中国临床药学杂志，1998，7(6)：305．
13. Lawrence KR, Nasraway SA. Conduction disturbances associated with administration of butyrophenone antipsychotics in the critically ill: a review of the literature. Pharmacotherapy, 1997, 17(3): 531-7.
14. Metzger E, Friedman R. Prolongation of the corrected QT and torsades de pointes cardiac arrhythmia associated with intravenous haloperidol in the medically ill. J Clin Psychopharmacol, 1993, 13(2): 128-32.
15. Jackson T, Ditmanson L, Phibbs B. Torsade de pointes and low-dose oral haloperidol. Arch Intern Med, 1997, 157(17): 2013-5.
16. Sharma ND, Rosman HS, Padhi ID et al. Torsades de Pointes associated with intravenous haloperidol in critically ill patients. Am J Cardiol, 1998, 81(2): 238-40.
17. Furrows DC. Cardiotoxicity associated with use of intravenous haloperidol. Aust N Z J Psychiatry, 1999, 33(2): 284.
18. O'Brien JM, Rockwood RP, Suh KI. Haloperidol-induced torsade de pointes. Ann Pharmacother, 1999, 33(10): 1046-50.
19. Johri S, Rashid H, Daniel PJ et al. Cardiopulmonary arrest secondary to haloperidol. Am J Emerg Med, 2000, 18(7): 839.
20. Welch R, Chue P. Antipsychotic agents and QT changes. J Psychiatry Neurosci, 2000, 25(2): 154-60.
21．刘宁，赵高苹．氟哌啶醇静脉滴注致死亡1例．中华精神科杂志，1999，32(3)：185．
22. Medlin RP, Ransom MM, Watts JA et al. Effect of ethanol, haloperidol, and lorazepam on cardiac conduction and contraction. J Cardiovasc Pharmacol, 1996, 28(6): 792-8.
23. Sugiyama A, Satoh Y, Hashimoto K. In vivo canine model comparison of cardiohemodynamic and electrophysiological effects of a new antipsychotic drug aripiprazole (OPC-14597) to haloperidol. Toxicol Appl Pharmacol, 2001, 173(2): 120-8.
24．石刚刚，马希贤，陈锦香等．氟哌啶醇对猪冠状动脉螺旋肌条作用的研究．中国药学杂志，1996，31(3)：142-144．
25．石刚刚，魏东升，许绍芬．阿片受体激动剂对猪冠状动脉肌条作用的研究．生理学报，1994，46(2)：176-180．
26．石刚刚，许绍芬．苯环利定对离体豚鼠心脏冠状动脉流量的影响．上海医科大学学报，1994，21(2)：93-96．
27．石刚刚，郑锦鸿，陈少刚．氟哌啶醇治疗不稳定性心绞痛5例分析．汕头大学医学院学报，1997，10(2)：33-34．
28. Satoh Y, Sugiyama A, Tamura K et al. Effect of magnesium sulfate on the haloperidol-induced QT prolongation assessed in the canine in vivo model under the monitoring of monophasic action potential. Jpn Circ J, 2000, 64(6): 445-51.
29. Kobayashi T, Ikeda K, Kumanishi T. Inhibition by various antipsychotic drugs of the G-protein-activated inwardly rectifying K(+) (GIRK) channels expressed in xenopus oocytes. Br J Pharmacol, 2000, 129(8): 1716-22.
30. Suessbrich H, Schonherr R, Heinemann SH, Attali B, Lang F, Busch AE. The inhibitory effect of the antipsychotic drug haloperidol on HERG potassium channels expressed in Xenopus oocytes. Br J Pharmacol, 1997, 120(5): 968-74.
31. Nakazawa K, Ito K, Koizumi S et al. Characterization of inhibition by haloperidol and chlorpromazine of a voltage-activated K+ current in rat phaeochromocytoma cells. Br J Pharmacol, 1995, 116(6): 2603-10.
32. Drici MD, Wang WX, Liu XK et al. Prolongation of QT interval in isolated feline hearts by antipsychotic drugs. J Clin Psychopharmacol, 1998, 18(6): 477-81.
33. Tisdale JE, Kambe JC, Chow MS et al. The effect of haloperidol on ventricular fibrillation threshold in pigs. Pharmacol Toxicol, 1991, 69(5): 327-9.
34. Ogata N, Narahashi T. Block of sodium channels by psychotropic drugs in single guinea-pig cardiac myocytes. Br J Pharmacol, 1989, 97(3): 905-13.
35. Ito K, Nakazawa K, Koizumi S et al. Inhibition by antipsychotic drugs of L-type Ca2+ channel current in PC12 cells. Eur J Pharmacol, 1996, 314(1-2): 143-50.
36. Fletcher EJ, Church J, MacDonald JF. Haloperidol blocks voltage-activated Ca2+ channels in hippocampal neurones. Eur J Pharmacol, 1994, 267(2): 249-52.
37．邱汉婴，李迪俊，毛焕元等．八厘麻毒素对兔心室不应期的影响．中国药理学通报，1997，13(3)：247-248．
38．邱汉婴，魏太星，张延荣等．雷尼替丁对兔正常心室和缺血心室不应期及室颤阈值的影响．中国药理学报，1993，14(3)：260-262．
39．孙安盛，张炜，刘国雄．异钩藤碱对麻醉兔心脏传导功能的影响．中国药理学与毒理学杂志，1995，9(2)：113-115．
40．张澍，陈明哲，郭静萱等．心脏电生理检查的基本方法．见：陈明哲主编．心脏病学(第一版)．北京：北京医科大学出版社，1999，392-401．
41．邱汉婴，王海鱼，李迪俊等．八厘麻毒素对离体灌注兔心脏电生理参数的影响．中国药理学通报，2000，16(1)：75-77．
42．马传庚，张宝恒．抗心律失常药实验法．见：徐叔云，卞如濂，陈修主编．药理实验方法学(第二版)．北京：人民卫生出版社，1991，1013-1021．
43. Cuffi ML, Vila E, Badia A. Effects of some antipsychotic drugs on cardiovascular catecholamine receptors in the rat. J Auton Pharmacol, 1989, 9(6): 397-409.
44. Magliozzi JR, Hollister LE. Elimination half-life and bioavailability of haloperidol in schizophrenic patients. J Clin Psychiatry, 1985, 46(1): 20-1.
45. Cheng YF, Paalzow LK, Bondesson U et al. Pharmacokinetics of haloperidol in psychotic patients. Psychopharmacology Berl, 1987, 91(4): 410-4.
46．张鸿燕，舒良，周东丰等．氟哌啶醇的药代动力学研究．中华神经精神科杂志，1995，28(6)：325-327．
47. Kudo S, Odomi M. Involvement of human cytochrome P450 3A4 in reduced haloperidol oxidation. Eur J Clin Pharmacol, 1998, 54(3): 253-9.
48. Iwahashi K, Nakamura K, Miyatake R et al. Cardiac effects of haloperidol and carbamazepine treatment. Am J Psychiatry, 1996, 153(1): 135.
49． Takeda M, Nishinuma K, Yamashita S et al. Serum haloperidol levels of schizophrenics receiving treatment for tuberculosis. Clin Neuropharmacol, 1986, 9(4) : 386-97
50． Kudo S, Ishizaki T. Pharmacokinetics of haloperidol: an update. Clin Pharmacokinet, 1999, 37(6) : 435-56．
51． Perrault LP, Denault AY, Carrier M et al. Torsades de pointes secondary to intravenous haloperidol after coronary bypass grafting surgery. Can J Anaesth, 2000, 47(3) : 251-4．
52． Douglas PH, Block PC. Corrected QT interval prolongation associated with intravenous haloperidol in acute coronary syndromes. Catheter Cardiovasc Interv, 2000, 50(3) : 352-5．
53． Di-Salvo TG, O'Gara PT. Torsade de pointes caused by high-dose intravenous haloperidol in cardiac patients. Clin Cardiol, 1995, 18(5) : 285-90．
54． Drici MD, Barhanin J. Cardiac K+ channels and drug-acquired long QT syndrome. Therapie, 2000, 55(1) : 185-93．
55． Aunsholt NA. Prolonged Q-T interval and hypokalemia caused by haloperidol. Acta Psychiatr Scand, 1989, 79(5) : 411-412．