title: Effects of 2-Hydroxypropyl-Beta-Cyclodextrin on Cardiovascular Signs of Amitriptyline Poisoning in a Rat Model.
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.
authors.affiliation: Division of Clinical Toxicology, Department of Medical Pharmacology, Dokuz Eylul University School of Medicine, Inciralti, 35340, Izmir, Turkey.
authors.forename: Burc
authors.initials: B
authors.lastname: Aydin
authors.affiliation: Division of Clinical Toxicology, Department of Medical Pharmacology, Dokuz Eylul University School of Medicine, Inciralti, 35340, Izmir, Turkey.
authors.forename: Nil
authors.initials: N
authors.lastname: Hocaoglu
authors.affiliation: Department of Histology and Embryology, Dokuz Eylul University School of Medicine, 35340, Izmir, Turkey.
authors.forename: Serap Cilaker
authors.initials: SC
authors.lastname: Micili
authors.affiliation: Department of Histology and Embryology, Dokuz Eylul University School of Medicine, 35340, Izmir, Turkey.
authors.forename: Bekir Ugur
authors.initials: BU
authors.lastname: Ergur
authors.affiliation: Division of Clinical Toxicology, Department of Medical Pharmacology, Dokuz Eylul University School of Medicine, Inciralti, 35340, Izmir, Turkey. sule.kalkan@deu.edu.tr.
authors.forename: Sule
authors.initials: S
authors.lastname: Kalkan
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000639:Amitriptyline; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D062186:Arterial Pressure / Q000187:drug effects; D066126:Cardiotoxicity; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002614:Chelating Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D004562:Electrocardiography; D005947:Glucose / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D017208:Rats, Wistar; D013997:Time Factors; D047392:beta-Cyclodextrins / Q000494:pharmacology*
chemical_list: D000931:Antidotes; D002614:Chelating Agents; D047392:beta-Cyclodextrins; D000639:Amitriptyline; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D005947:Glucose
keywords: 2-Hydroxypropyl-beta-cyclodextrin; Amitriptyline; HPBCD; Poisoning; Toxicity