Effects of in vitro Amitriptyline, Fluoxetine, Tranylcypromine and Venlafaxine on Saphenous Vein Grafts

Abstract Objective: In this study, we aimed to examine the effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts in coronary artery bypass graft surgeries. Methods: 59 patients (40 males and 19 females; mean age 65.1 years, distribution: 45-84 years) who had coronary artery bypass graft surgery between February 2014 and May 2016 were included in the study. After the saphenous vein grafts with intact and denuded endothelium were precontracted with 3×10-6M phenylephrine, amitriptyline, fluoxetine and tranylcypromine were cumulatively added to isolated organ baths in the range of 10-11-3x10-5M, while venlafaxine was added in the range of 10-9-3×10-5M. Then, the antidepressant-induced relaxation responses were recorded isometrically. Results: While the relaxation response of amitriptyline at -6.42 (Log M) was 74.6%, the response at -6.32 (Log M) was 75.5%. While the relaxation response at -6.46 (Log M) of fluoxetine was 68.02%, the response at -6.02 (Log M) was 72.12%. While the relaxation response of tranylcypromine at -7.53 (Log M) was 61.13%, the response at -7.23 (Log M) was 65.53%. While the relaxation response of venlafaxine at -6.21 (Log M) was 29.98%, the response at -5.90 (Log M) was 32.96%. Conclusion: The maximum relaxation at minimum and maximum therapeutic concentrations was obtained with amitriptyline, fluoxetine and tranylcypromine, and the minimum relaxation was obtained with venlafaxine. The relaxation responses were independent of the endothelium.

摘要
研究目的：本研究旨在探讨阿米替林、氟西汀、反苯环丙胺及文拉法辛对冠状动脉旁路移植术中隐静脉移植物的影响。
方法：纳入2014年2月至2016年5月期间接受冠状动脉旁路移植术的59例患者（男性40例，女性19例；平均年龄65.1岁，年龄分布范围为45~84岁）。将内皮完整及内皮剥脱的隐静脉移植物以3×10^-6 M去氧肾上腺素预收缩后，依次向离体器官浴槽中累积加入浓度范围为10^-11~3×10^-5 M的阿米替林、氟西汀及反苯环丙胺；文拉法辛的给药浓度范围则为10^-9~3×10^-5 M。随后采用等长记录方式记录抗抑郁药物诱导的血管舒张反应。
结果：阿米替林在-6.42（Log M）浓度下的舒张反应率为74.6%，在-6.32（Log M）浓度下为75.5%。氟西汀在-6.46（Log M）浓度下的舒张反应率为68.02%，在-6.02（Log M）浓度下为72.12%。反苯环丙胺在-7.53（Log M）浓度下的舒张反应率为61.13%，在-7.23（Log M）浓度下为65.53%。文拉法辛在-6.21（Log M）浓度下的舒张反应率为29.98%，在-5.90（Log M）浓度下为32.96%。
结论：在最低与最高治疗浓度范围内，阿米替林、氟西汀及反苯环丙胺可实现最大程度的血管舒张，而文拉法辛的舒张效果最弱。且该类抗抑郁药物诱导的舒张反应均不依赖于血管内皮的完整性。