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. 2017 Sep;22(5):e12441.
doi: 10.1111/anec.12441. Epub 2017 Feb 25.

Antazoline-insights into drug-induced electrocardiographic and hemodynamic effects: Results of the ELEPHANT II substudy

Roman Piotrowski  1 , Joanna Giebułtowicz  2 , Jakub Baran  1 , Agnieszka Sikorska  1 , Dagmara Gralak-Łachowska  1 , Małgorzata Soszyńska  1 , Piotr Wroczyński  2 , Piotr Kułakowski  1
Affiliations

Antazoline-insights into drug-induced electrocardiographic and hemodynamic effects: Results of the ELEPHANT II substudy

Roman Piotrowski et al. Ann Noninvasive Electrocardiol. 2017 Sep.

Abstract

Background: Antazoline is an old antihistaminic and new antiarrhythmic agent with unknown mechanisms of action which recently has been shown to effectively terminate atrial fibrillation. The aim of study was to examine the effects of antazoline on hemodynamic and ECG parameters.

Methods: Antazoline was given intravenously in three 100 mg boluses to 10 healthy volunteers (four males, mean age 40 + 11 years). Hemodynamic and ECG parameters were measured using impedance cardiography [systolic (sBP), diastolic (dBP), mean (mBP) blood pressure, stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR) and heart rate (HR), P wave, PR interval, QRS complex, QT and corrected QT (QTcF) interval]. Plasma concentration of antazoline was also measured.

Results: Antazoline caused significant prolongation of P wave, QRS as well as QT and QTcF (101 ± 10 vs 110 ± 16 ms, p < .05, and 101 ± 12 vs 107 ± 12 ms, p < .05, 399 ± 27 vs 444 ± 23 ms, p < .05, and 403 ± 21 vs 448 ± 27 ms, p < .05, respectively). Also, a significant decrease in SV was noted (94.9 ± 21.8 vs 82.4 ± 19.6 ml, p < .05). A significant correlation between changes in plasma drug concentration and changes in CO, HR, and dBP was found.

Conclusions: Antazoline impairs slightly hemodynamics, significantly reducing SV. Significant prolongation of P wave and QRS duration corresponds to drug-induced prolongation of conduction, whereas QT prolongation represents drug-induced prolongation of repolarization.

Keywords: antazoline; antazoline concentration; antiarrhythmic agent; atrial fibrillation; hemodynamic and electrocardiographic effects.

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Conflict of interest statement

All authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Mean ± SD values of examined ECG parameters at prespecified time points
Figure 2
Figure 2
Relative drug‐induced ECG changes (Δ—change from baseline)
Figure 3
Figure 3
Mean ± SD values of examined hemodynamic parameters at prespecified time points. sBP, systolic blood pressure; dBP, diastolic blood pressure; mBP, mean blood pressure; SV, stroke volume; CO, cardiac output; TPR, total peripheral resistance
Figure 4
Figure 4
Relative drug‐induced hemodynamic parameters changes (Δ—change from baseline)
Figure 5
Figure 5
Comparison between the concentration of antazoline (mean and individual values) and QTcF interval
Figure 6
Figure 6
Scatter plot with mean antazoline concentrations versus change‐from‐baseline QTcF (∆QTcF). Numbers depict time point measurements
Figure 7
Figure 7
Correlation curves between plasma concentration of antazoline and changes in ECG and hemodynamic parameters. HR, heart rhythm; dBP, diastolic blood pressure; CO, cardiac output; SV, stroke volume; mBP, mean blood pressure; TPR, total peripheral resistance
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