Salameh Aida, Halling Michelle, Seidel Thomas, Dhein Stefan
Clinic for Pediatric Cardiology, Heart Centre, University of Leipzig, Leipzig, Germany.
Clinic for Cardiac Surgery, Heart Centre, University of Leipzig, Leipzig, Germany.
Clin Exp Pharmacol Physiol. 2015 Dec;42(12):1258-65. doi: 10.1111/1440-1681.12485.
Pharmacological cardiac organ protection during cardiopulmonary bypass presents an opportunity for improvement. A number of different strategies have been established to minimize ischemia/reperfusion-induced damage to the heart. Among these, cardioplegia with histidine-tryptophan-ketoglutarate solution and hypothermia are the most frequently used regimens. The antibiotic minocycline has been used in this context for neuroprotection. The aim of the current study was to evaluate whether the application of minocycline prior to cardioplegia exerts a protective effect on cardiac muscle. For this purpose, this study investigated six rabbit hearts with minocycline treatment (1 μmol/L) and six without in a Langendorff model of 90 min cold cardioplegic arrest using Custodiol followed by a 30 min recovery phase. Histological analysis of cardiac muscle revealed that markers of apoptosis, oxidative and nitrosative stress were significantly lower in the minocycline group, whereas adenosine triphosphate (ATP)- and malondialdehyde (MDA)-levels and O2-consumption were not affected by minocycline. Functionally, recovery of dP/dt (max) and dP/dt (min) was significantly faster in the minocycline group than in control. This leads to the conclusion that adding minocycline to the cardioplegic solution may improve left ventricular recovery after cardioplegic arrest involving reduced pro-apoptotic effects.
体外循环期间的药理学心脏器官保护存在改进的机会。已经建立了许多不同的策略来最小化缺血/再灌注引起的心脏损伤。其中,使用组氨酸-色氨酸-酮戊二酸溶液的心脏停搏液和低温是最常用的方案。抗生素米诺环素已在此背景下用于神经保护。本研究的目的是评估在心脏停搏液之前应用米诺环素是否对心肌发挥保护作用。为此,本研究在使用Custodiol进行90分钟冷心脏停搏的Langendorff模型中,对六只接受米诺环素治疗(1 μmol/L)的兔心脏和六只未接受米诺环素治疗的兔心脏进行了研究,随后有30分钟的恢复阶段。心肌的组织学分析显示,米诺环素组中凋亡、氧化和亚硝化应激的标志物显著降低,而三磷酸腺苷(ATP)和丙二醛(MDA)水平以及氧气消耗不受米诺环素影响。在功能上,米诺环素组中dP/dt(max)和dP/dt(min)的恢复明显快于对照组。由此得出结论,在心脏停搏液中添加米诺环素可能会改善心脏停搏后左心室的恢复,包括减少促凋亡作用。