Electrophysiological effects of haloperidol on isolated rabbit Purkinje fibers and guinea pigs papillary muscles under normal and simulated ischemia.
OBJECTIVE
Overdoses of haloperidol are associated with major ventricular arrhythmias, cardiac conduction block, and sudden death. The aim of this experiment was to study the effect of haloperidol on the action potentials in cardiac Purkinje fibers and papillary muscles under normal and simulated ischemia conditions in rabbits and guinea pigs.


METHODS
Using the standard intracellular microelectrode technique, we examined the effects of haloperidol on the action potential parameters [action potential amplitude (APA), phase 0 maximum upstroke velocity (V(max)), action potential amplitude at 90% of repolarization (APD(90)), and effective refractory period (ERP)] in rabbit cardiac Purkinje fibers and guinea pig cardiac papillary cells, in which both tissues were under simulated ischemic conditions.


RESULTS
Under ischemic conditions, different concentrations of haloperidol depressed APA and prolonged APD(90) in a concentration-dependent manner in rabbit Purkinje fibers. Haloperidol (3 micromol/L) significantly depressed APA and prolonged APD(90), and from 1 micromol/L, haloperidol showed significant depression on V(max); ERP was not significantly affected. In guinea pig cardiac papillary muscles, the thresholds of significant reduction in APA, V(max), EPR, and APD(90) were 10, 0.3, 1, and 1 mumol/L, respectively, for haloperidol.


CONCLUSIONS
Compared with cardiac conductive tissues, papillary muscles were more sensitive to ischemic conditions. Under ischemia, haloperidol prolonged ERP and APD(90) in a concentration-dependent manner and precipitated the decrease in V(max) induced by ischemia. The shortening of ERP and APD(90) in papillary muscle action potentials may be inhibited by haloperidol.
Yan
Dong
D
Department of Pharmacology, Xinjiang Medical University, Urumqi, China.
Cheng
Lu-feng
LF
Song
Hong-Yan
HY
Turdi
Subat
S
Kerram
Parhat
P
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006220:Haloperidol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D012032:Refractory Period, Electrophysiological / Q000187:drug effects
D006220:Haloperidol