Comparison of the Apoptotic Effects of Topically Applied Papaverine, Diltiazem, and Nitroprusside to Internal Thoracic Artery

Abstract Objective: To detect and to compare the apoptotic effects of intraoperatively topically applied diltiazem, papaverine, and nitroprusside. Methods: Internal thoracic artery segments of ten patients were obtained during coronary bypass grafting surgery. Each internal thoracic artery segment was divided into four pieces and immersed into four different solutions containing separately saline (Group S), diltiazem (Group D), papaverine (Group P), and nitroprusside (Group N). Each segment was examined with both hematoxylin-eosin and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in order to determine and quantify apoptosis. Results: Apoptotic cells were counted in 50 microscopic areas of each segment. No significant difference was observed among the four groups according to hematoxylin-eosin staining. However, the TUNEL method revealed a significant increase in mean apoptotic cells in the diltiazem group when compared with the other three groups (Group S=4.25±1.4; Group D=13.31±2.8; Group N=9.48±2.09; Group P=10.75±2.37). The differences between groups were significant (P=0.0001). No difference was observed between the samples of the diabetic and non-diabetic patients in any of the study groups. Conclusion: The benefit of topically applied vasodilator drugs must outweigh the potential adverse effects. In terms of apoptosis, diltiazem was found to have the most deleterious effects on internal thoracic artery graft segments. Of the analyzed medical agents, nitroprusside was found to have the least apoptotic activity, followed by papaverine. Diabetes did not have significant effect on the occurrence of apoptosis in left internal thoracic artery grafts.

摘要 目的：探讨术中局部应用地尔硫卓、罂粟碱及硝普钠的细胞凋亡诱导效应并进行对比分析。方法：选取10例冠状动脉旁路移植术患者术中获取的胸廓内动脉段标本，将每段动脉均分为四份，分别浸入四种不同溶液：生理盐水（S组）、地尔硫卓（D组）、罂粟碱（P组）及硝普钠（N组）。采用苏木精-伊红（hematoxylin-eosin）染色法与末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记法（terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling，TUNEL）对每份标本进行检测，以定量并判定细胞凋亡情况。结果：对每份标本的50个显微视野进行凋亡细胞计数。苏木精-伊红染色结果显示，四组间无统计学差异。但TUNEL法检测结果表明，与其余三组相比，地尔硫卓组的平均凋亡细胞数显著升高（S组：4.25±1.4；D组：13.31±2.8；N组：9.48±2.09；P组：10.75±2.37），组间差异具有显著统计学意义（P=0.0001）。糖尿病患者与非糖尿病患者的标本在各研究组中均未观察到显著差异。结论：局部应用血管舒张药物的临床获益需大于其潜在不良反应。就细胞凋亡而言，地尔硫卓对胸廓内动脉移植物段的损伤效应最为显著。在所分析的受试药物中，硝普钠的凋亡诱导活性最低，其次为罂粟碱。糖尿病状态对左胸廓内动脉移植物的细胞凋亡发生无显著影响。