title: Evaluation of the cardiovascular effects of varenicline in rats.
abstract: BACKGROUND
  Cardiovascular disease is an important cause of morbidity and mortality among tobacco users. Varenicline is widely used worldwide to help smoking cessation, but some published studies have reported associated cardiovascular events.
  
  
  OBJECTIVE
  To determine the cardiovascular toxicity induced by varenicline in rats.
  
  
  METHODS
  We randomly separated 34 rats into two groups: 1) the control group (given only distilled water orally, n=10) and the varenicline group (given 9 μg/kg/day varenicline on days 1-3, 9 μg/kg twice daily on days 4-7, and 18 μg/kg twice daily on days 8-90 [total 83 days], n=24). Each group was then subdivided equally into acute and chronic subgroups, and all rats in these groups were euthanized with anesthesia overdose on days 45 and 90, respectively. Body and heart weights, hemodynamic (mean oxygen saturation, mean blood pressure, and heart rate, electrocardiographic (PR, QRS, and QT intervals) biochemical (oxidants and antioxidants), and histopathological analyses (including immunostaining) were performed.
  
  
  RESULTS
  Acute varenicline exposure resulted in loss of body weight, while chronic varenicline exposure caused heart weight loss and decreased mean blood pressure, induced lipid peroxidation, and reduced antioxidant activity. Both acute and chronic varenicline exposure caused impairment of mean oxygen saturation. QT interval was prolonged in the chronic varenicline group, while PR interval prolongation was statistically significant in both the control and acute varenicline groups. Caspase-9 activity was also significantly increased by chronic exposure. Moreover, histopathological observations revealed severe morphological heart damage in both groups.
  
  
  CONCLUSIONS
  Adverse effects of chronic varenicline exposure on cardiovascular tissue were confirmed by our electrocardiographic, biochemical, and histopathological analyses. This issue needs to be investigated with new experimental and clinical studies to evaluate the exact mechanism(s) of the detrimental effects of varenicline. Physicians should bear in mind the toxic effects of varenicline on the cardiovascular system when prescribing it for smoking cessation.
authors.affiliation: Department of Family Medicine, Malatya, Turkey.
authors.forename: Engin Burak
authors.initials: EB
authors.lastname: Selçuk
authors.affiliation: Inonu University Medical Faculty, Malatya, Turkey.
authors.forename: Meltem
authors.initials: M
authors.lastname: Sungu
authors.affiliation: Department of Pharmacology, Inonu University Medical Faculty, Malatya, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Parlakpinar
authors.affiliation: Department of Cardiology, Inonu University Medical Faculty, Malatya, Turkey.
authors.forename: Necip
authors.initials: N
authors.lastname: Ermiş
authors.affiliation: Department of Histology and Embryology, Inonu University Medical Faculty, Malatya, Turkey.
authors.forename: Elif
authors.initials: E
authors.lastname: Taslıdere
authors.affiliation: Department of Histology and Embryology, Inonu University Medical Faculty, Malatya, Turkey.
authors.forename: Nigar
authors.initials: N
authors.lastname: Vardı
authors.affiliation: Department of Pulmonary Medicine, Inonu University Medical Faculty, Malatya, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Yalçınsoy
authors.affiliation: Department of Pharmacology, Inonu University Medical Faculty, Malatya, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Sagır
authors.affiliation: Department of Physiology, Inonu University Medical Faculty, Malatya, Turkey.
authors.forename: Alaaddin
authors.initials: A
authors.lastname: Polat
authors.affiliation: Department of Medical Ethics, Inonu University Medical Faculty, Malatya, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Karatas
authors.affiliation: Department of Family Medicine, Malatya, Turkey.
authors.forename: Burcu
authors.initials: B
authors.lastname: Kayhan-Tetik
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D053453:Caspase 9 / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018722:Nicotinic Agonists / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D018570:Risk Assessment; D013997:Time Factors; D061485:Tobacco Use Cessation Devices / Q000009:adverse effects*; D000068580:Varenicline / Q000633:toxicity*; D015431:Weight Loss
chemical_list: D000975:Antioxidants; D018722:Nicotinic Agonists; C506435:Casp9 protein, rat; D053453:Caspase 9; D000068580:Varenicline
keywords: cardiovascular; electrocardiogram; histopathological evaluation; rat; smoking; varenicline