Objectives. Doxapram hydrochloride is a respiratory stimulant that has an inhibitory effect on myocardial IK1 potassium channels and is thought to increase membrane instability and excitability in myocardial cells. We examined the arrhythmogenic effects of doxapram hydrochloride in a rat model of halothane adrenaline-induced arrhythmia. Methods. Thirteen female Wistar rats (12–14 weeks old) were used in the study. Animals were anesthetized with inhalation of halothane to permit observation of the effects of doxapram hydrochloride on halothane adrenaline-induced arrhythmia. Time-dependent changes in ECG repolarization characteristics (QT, QTc, JTp, JT, and Tp-e intervals) were studied. Results. Doxapram hydrochloride itself did not induce arrhythmia but did induce bidirectional ventricular tachycardia after addition of adrenaline. Conclusion. Drug-induced impairment of intracellular Ca2+ regulation caused BVT in the absence of genetic abnormalities in proteins in the sarcoplasmic reticulum. 1. Introduction Doxapram hydrochloride is a respiratory stimulant that is mainly used for anesthesia awareness in adult patients and treatment of apneic episodes in low birth weight infants. The mechanism of action of doxapram hydrochloride involves stimulation of the respiratory center, that is, effects on K+ channels such as TASK-1 and -3 in carotid bodies, which depolarizes membrane potentials and increases secretion of neurotransmitters [1, 2]. However, the pharmacological action of doxapram hydrochloride in other organs has not been studied extensively. Halothane increases myocardial sensitivity to adrenaline, and adrenaline administered under halothane anesthesia readily causes premature ventricular contraction, resulting in fatal ventricular fibrillation; therefore, this combination is used as an anesthetic-induced arrhythmic model [3, 4]. We have found that clinical doses of doxapram hydrochloride have no effect on the heart conduction system in rats [5], while doxapram hydrochloride at high doses prolongs the myocardial repolarization interval and causes deterioration of halothane adrenaline-induced arrhythmia. In this study, we focused on doxapram hydrochloride-induced bidirectional ventricular tachycardia (BVT) that is a rare entity occurring in conditions associated with intracellular calcium overload. Delayed afterdepolarizations occurring in different zones of the conduction system are thought to best explain its mechanism [6]. We studied changes in ECG repolarization characteristics before and after onset of tachycardia. 2. Methods 2.1. Animals Female
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