Alexopoulos Panagiotis, Panoutsopoulou Konstantina, Vogiatzis George, Koletsis Efstratios, Dougenis Dimitrios, Tsopanoglou Nikos E
*Department of Pharmacology, Medical School, University of Patras, Patras, Greece;†Department of Cardiothoracic Surgery, University Hospital of Patras, Patras, Greece; and‡Genesis Pharma S.A., Athens, Greece.
J Cardiovasc Pharmacol. 2017 Jul;70(1):34-41. doi: 10.1097/FJC.0000000000000492.
Exenatide and cyclosporine A have been shown to moderately protect against myocardial reperfusion injury leading to reduction of infarct size in patients. Our objective was to investigate whether the combined treatment with exenatide (glucagon-like peptide 1 receptor agonist) and cyclosporine A or parstatin 1-26 (inhibitors of mitochondrial permeability transition pore and/or inflammation) is more beneficial than either agent alone. Rabbits underwent 40 minutes of ischemia and 120 minutes of reperfusion. Intravenous bolus administration of exenatide or cyclosporine A, 10 minutes before reperfusion, reduced infarct size by 38% (P < 0.05) and 40% (P < 0.05), and cardiac troponin I (cTnI) plasma levels by 48% (P < 0.05) and 36% (P < 0.05), respectively, compared with control. The combined administration of both agents resulted in an additive decrease of infarct size by 55% (P < 0.05) and cTnI release by 61% (P < 0.05). Also, combined treatment of exenatide and parstatin 1-26 enhanced infarct size reduction (62%, P < 0.05), compared with monotherapies (41% for parstatin 1-26, P < 0.05; 43% for exenatide, P < 0.05). In contrast, the combined administration of parstatin 1-26 and cyclosporine A canceled out the cardioprotective effects observed by monotherapies. These results suggest that, for the therapy of myocardial reperfusion injury the combined administration of exenatide and cyclosporine A or parstatin 1-26 is more effective than monotherapies and may provide advantageous clinical outcome.
艾塞那肽和环孢素A已被证明可适度预防心肌再灌注损伤，从而缩小患者的梗死面积。我们的目的是研究艾塞那肽（胰高血糖素样肽1受体激动剂）与环孢素A或帕他汀1 - 26（线粒体通透性转换孔和/或炎症抑制剂）联合治疗是否比单独使用任何一种药物更有益。对兔子进行40分钟的缺血和120分钟的再灌注。在再灌注前10分钟静脉推注艾塞那肽或环孢素A，与对照组相比，梗死面积分别减少38%（P < 0.05）和40%（P < 0.05）；心肌肌钙蛋白I（cTnI）血浆水平分别降低48%（P < 0.05）和36%（P < 0.05）。两种药物联合给药使梗死面积进一步减少55%（P < 0.05），cTnI释放减少61%（P < 0.05）；此外，与单一疗法相比，艾塞那肽和帕他汀1 - 26联合治疗使梗死面积缩小更显著（62%；P < 0.05），单一疗法中帕他汀1 - 26使梗死面积缩小41%（P < 0.05）；艾塞那肽使梗死面积缩小43%（P < 0.05）。相比之下，帕他汀1 - 26和环孢素A联合给药抵消了单一疗法所观察到的心脏保护作用。这些结果表明，对于心肌再灌注损伤的治疗，艾塞那肽与环孢素A或帕他汀1 - 26联合给药比单一疗法更有效，可能会带来有利的临床结果。
