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Effects of 2-Hydroxypropyl-Beta-Cyclodextrin on Cardiovascular Signs of Amitriptyline Poisoning in a Rat Model

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Abstract

The aim of this study was to investigate the efficacy of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) as an antidotal treatment for the in vivo cardiovascular effects of amitriptyline poisoning. Experiments were carried out on 33 Wistar rats. To evaluate cardiovascular effects of HPBCD, rats were infused with dextrose or HPBCD. In the poisoning model, amitriptyline (0.94 mg/kg/min) was infused until the mean arterial blood pressure (MAP) dropped to 50 % of the baseline. Following amitriptyline infusion, dextrose, low-dose HPBCD (4.19 mg/kg/min), or high-dose HPBCD (16.76 mg/kg/min) was infused, and MAP, heart rate (HR), and electrocardiogram were recorded for 60 min. Hearts were examined for tissue damage and apoptosis. HPBCD infusion alone did not yield significant difference for MAP, HR, QRS duration, QT interval, and cardiac tissue damage when compared to dextrose (p > 0.05). In the poisoning model, MAP and HR decreased, while QRS duration and QT interval prolonged significantly following amitriptyline infusion (p < 0.0167). Dextrose, low-dose HPBCD, and high-dose HPBCD infusion similarly corrected MAP, HR, QRS duration, and QT interval values at the end-experiment time point (p > 0.05). Histological scores for tissue damage and apoptosis showed no significant difference between the groups (p > 0.05). Based on our results, HPBCD did not show cardiovascular toxicity, while it was not more effective than dextrose for the treatment of amitriptyline poisoning. Further antidotal studies of cyclodextrins with higher doses and/or binding affinities are needed for poisonings.

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Acknowledgments

The results of this study were presented as a poster at the 23rd National Pharmacology Congress of Turkish Pharmacological Society.

Funding

This study was funded by Dokuz Eylul University Scientific Research Projects Coordination Unit (Grant No.: 2013.KB.SAG.022). The funder played no role in the design, conduct, or dissemination of the study.

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Authors and Affiliations

  1. Division of Clinical Toxicology, Department of Medical Pharmacology, Dokuz Eylul University School of Medicine, Inciralti, 35340, Izmir, Turkey

    Burc Aydin, Nil Hocaoglu & Sule Kalkan

  2. Department of Histology and Embryology, Dokuz Eylul University School of Medicine, 35340, Izmir, Turkey

    Serap Cilaker Micili & Bekir Ugur Ergur

Authors
  1. Burc Aydin
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  2. Nil Hocaoglu
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  3. Serap Cilaker Micili
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  4. Bekir Ugur Ergur
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  5. Sule Kalkan
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Corresponding author

Correspondence to Sule Kalkan.

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Conflict of interest

B Aydin has received personal fees and travel and meeting grants from EU FP7 Project ‘European Clinical Research Infrastructure Network—Integrating Activity.’ The other authors declare no competing interest.

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Aydin, B., Hocaoglu, N., Micili, S.C. et al. Effects of 2-Hydroxypropyl-Beta-Cyclodextrin on Cardiovascular Signs of Amitriptyline Poisoning in a Rat Model. Cardiovasc Toxicol 16, 374–380 (2016). https://doi.org/10.1007/s12012-015-9349-4

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  • DOI: https://doi.org/10.1007/s12012-015-9349-4

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