Why the study?
Does doxapram hydrochloride aggravate adrenaline-induced arrhythmias in a rat model?
Does doxapram hydrochloride aggravate adrenaline-induced arrhythmias in a rat model?
Doxapram hydrochloride aggravates adrenaline-induced arrhythmias by causing bidirectional ventricular tachycardia in a rat model, likely due to drug-induced impairment of intracellular Ca2+ regulation.
Hypothesis-generating in rat model; leaves open human arrhythmia risk and should not change practice.
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 Ca(2+) regulation caused BVT in the absence of genetic abnormalities in proteins in the sarcoplasmic reticulum.
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Oikawa et al. (2014) studied this question.
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