Skeffington Katie L, Mohamed Ahmed Eltayeb, Rapetto Filippo, Chanoit Guillaume, Bond Andrew R, Vardeu Antonella, Ghorbel Mohamed T, Suleiman M-Saadeh, Caputo Massimo
Bristol Heart Institute, University of Bristol, Research Floor Level 7, Bristol Royal Infirmary, Bristol, United Kingdom.
Department of Cardiac Surgery, Bristol Royal Infirmary, Bristol, United Kingdom.
Front Cardiovasc Med. 2023 Jun 7;10:1194645. doi: 10.3389/fcvm.2023.1194645. eCollection 2023.
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.
小儿心脏直视手术中使用的心脏停搏液心脏保护策略仍不尽人意。西地那非是一种磷酸二酯酶5(PDE - 5)抑制剂,在多种实验模型中已显示出对缺血/再灌注损伤具有心脏保护作用,因此本研究在仔猪体外循环和心脏停搏模型中,使用冷和温心脏停搏方案,测试了在心脏停搏液中添加西地那非的效果。将仔猪麻醉后置于冠状动脉体外循环(CPB),夹闭主动脉,用含或不含西地那非(10 nM)的心脏停搏液使心脏停搏60分钟。移除夹闭钳(再灌注)20分钟后,尝试使仔猪脱离CPB。再灌注60分钟后进行处死。在整个实验过程中,采集血液和左心室组织样本,用于分析选定的代谢物(使用高效液相色谱法)和肌钙蛋白I。在冷和温心脏停搏方案中,均有证据表明添加西地那非可使ATP水平恢复更快,改善能量状态(一种代谢通量的度量),并改变两种嘌呤分解代谢产物次黄嘌呤和肌苷的释放。在所研究的短时间内对肌钙蛋白释放没有影响。总之,在小儿CPB手术的转化动物模型中,在心脏停搏液中添加西地那非可改善心脏能量代谢。