Authors: YAN, Dong; CHENG, Lu-feng; SONG, Hong-yan; TURDI, Subat; KERRAM, Parhat

Source: Acta Pharmacologica Sinica, Volume 28, Number 8, August 2007 , pp. 1155-1160(6)

Publisher: Wiley-Blackwell

Abstract:

Aim: 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 (APD₉₀), 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 APD₉₀ in a concentration-dependent manner in rabbit Purkinje fibers. Haloperidol (3 μmol/L) significantly depressed APA and prolonged APD₉₀, and from 1 μmol/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 APD₉₀ were 10, 0.3, 1, and 1 μmol/L, respectively, for haloperidol. Conclusion: Compared with cardiac conductive tissues, papillary muscles were more sensitive to ischemic conditions. Under ischemia, haloperidol prolonged ERP and APD₉₀ in a concentration-dependent manner and precipitated the decrease in V_max induced by ischemia. The shortening of ERP and APD₉₀ in papillary muscle action potentials may be inhibited by haloperidol.

Keywords: haloperidol; Purkinje fibers; ischemic; action potential; arrhythmia

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1745-7254.2007.00572.x

Affiliations: 1: Department of Pharmacology, Xinjiang Medical University, Urumqi 830054, China

Publication date: 2007-08-01

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