Datasheet1_The effect of cardioplegic supplementation with sildenafil on cardiac energetics in a piglet model of cardiopulmonary bypass and cardioplegic arrest with warm or cold cardioplegia.docx

Cardioplegic cardioprotection strategies used during paediatric open-heart surgery remain suboptimal. Sildenafil, a phosphodiesterase 5 (PDE-5) inhibitor, has been shown to be cardioprotective against ischemia/reperfusion injury in a variety of experimental models and this study therefore tested the efficacy of supplementation of cardioplegia with sildenafil in a piglet model of cardiopulmonary bypass and arrest, using both cold and warm cardioplegia protocols. Piglets were anaesthetized and placed on coronary pulmonary bypass (CPB), the aorta cross-clamped and the hearts arrested for 60 min with cardioplegia with or without sildenafil (10 nM). Twenty minutes after removal of cross clamp (reperfusion), attempts were made to wean the pigs from CPB. Termination was carried out after 60 min reperfusion. Throughout the protocol blood and left ventricular tissue samples were taken for analysis of selected metabolites (using HPLC) and troponin I. In both the cold and warm cardioplegia protocols there was evidence that sildenafil supplementation resulted in faster recovery of ATP levels, improved energy charge (a measure of metabolic flux) and altered release of hypoxanthine and inosine, two purine catabolites. There was no effect on troponin release within the studied short timeframe. In conclusion, sildenafil supplementation of cardioplegia resulted in improved cardiac energetics in a translational animal model of paediatric CPB surgery.

儿科心脏直视手术中所采用的心脏停搏液心肌保护策略仍未达到最优水平。作为磷酸二酯酶5（PDE-5）抑制剂，西地那非在多种实验模型中被证实可对抗缺血再灌注损伤并发挥心肌保护作用，因此本研究采用冷、温两种心脏停搏液灌注方案，在心肺旁路（CPB）与心脏停搏仔猪模型中测试了西地那非补充心脏停搏液的疗效。实验中将仔猪麻醉后建立心肺旁路模型，夹闭主动脉，使用含或不含10nM西地那非的心脏停搏液使心脏停搏60分钟；移除主动脉夹（再灌注）20分钟后，尝试将仔猪脱离CPB，并于再灌注60分钟后结束实验。本实验全程采集血液及左心室组织样本，通过高效液相色谱法（HPLC）分析选定的代谢物并检测肌钙蛋白I水平。冷、温两种心脏停搏液灌注方案下均证实，补充西地那非可加快三磷酸腺苷（ATP）水平恢复、改善能量负荷（代谢通量的衡量指标），并改变次黄嘌呤与肌苷这两种嘌呤分解代谢物的释放情况；在本研究的短期实验周期内，西地那非对肌钙蛋白释放无显著影响。综上，在儿科CPB手术的转化动物模型中，向心脏停搏液中补充西地那非可改善心肌能量代谢状态。