Selçuk Engin Burak, Sungu Meltem, Parlakpinar Hakan, Ermiş Necip, Taslıdere Elif, Vardı Nigar, Yalçınsoy Murat, Sagır Mustafa, Polat Alaaddin, Karatas Mehmet, Kayhan-Tetik Burcu
Department of Family Medicine, Malatya, Turkey.
Inonu University Medical Faculty, Malatya, Turkey.
Drug Des Devel Ther. 2015 Oct 22;9:5705-17. doi: 10.2147/DDDT.S92268. eCollection 2015.
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.
To determine the cardiovascular toxicity induced by varenicline in rats.
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.
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.
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.
心血管疾病是烟草使用者发病和死亡的重要原因。伐尼克兰在全球范围内广泛用于帮助戒烟，但一些已发表的研究报告了相关的心血管事件。
确定伐尼克兰对大鼠的心血管毒性。
我们将34只大鼠随机分为两组：1）对照组（仅口服蒸馏水，n = 10）和伐尼克兰组（第1 - 3天给予9μg/kg/天的伐尼克兰，第4 - 7天每天两次给予9μg/kg，第8 - 90天每天两次给予18μg/kg[共83天]，n = 24）。然后将每组平均分为急性和慢性亚组，这些组中的所有大鼠分别在第45天和第90天用过量麻醉剂安乐死。进行了体重和心脏重量、血流动力学（平均血氧饱和度、平均血压和心率）、心电图（PR、QRS和QT间期）、生化（氧化剂和抗氧化剂）以及组织病理学分析（包括免疫染色）。
急性伐尼克兰暴露导致体重减轻，而慢性伐尼克兰暴露导致心脏重量减轻、平均血压降低、诱导脂质过氧化并降低抗氧化活性。急性和慢性伐尼克兰暴露均导致平均血氧饱和度受损。慢性伐尼克兰组的QT间期延长，而对照组和急性伐尼克兰组的PR间期延长具有统计学意义。慢性暴露还使半胱天冬酶 - 9活性显著增加。此外，组织病理学观察显示两组均有严重的心脏形态损伤。
我们的心电图、生化和组织病理学分析证实了慢性伐尼克兰暴露对心血管组织的不良影响。需要通过新的实验和临床研究来调查这个问题，以评估伐尼克兰有害作用的确切机制。医生在为戒烟开伐尼克兰处方时应牢记其对心血管系统的毒性作用。
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