Vento AE, Rämö OJ, Pesonen EJ, Heikkilä L, Nissinen E, Holopainen A, Mattila SP
Department of Thoracic and Cardiovascular Surgery, Helsinki University Central Hospital, Helsinki, Finland
Int J Angiol. 1999 Jan;8(1):16-21. doi: 10.1007/BF01616836.
During aortic cross-clamping, the myocardium suffers from global ischemia, which is followed by reperfusion after declamping. The generation of free oxygen radicals increases during reperfusion, resulting in arrhythmias and impaired cardiac function. This study was conducted to evaluate the effect of a novel antioxidant nitecapone (NC) on cardiac reperfusion injury in vivo. Twelve pigs were anesthetized and after sternotomy the aorta and the right atrium were cannulated for cardiopulmonary bypass. The heart was arrested with either +4 degreesC crystalloid cardioplegia alone in the control group (n = 6) or cardioplegia with NC (50 µM) added in the NC group (n = 6). Cardioplegia was added every 20 minutes. After 1 hour of aortic cross-clamping, blood samples for oxidative stress analysis were taken, and hemodynamic profile surveillance continued for 90 minutes. Heart rate (p = 0.04) and left ventricular end diastolic pressure (LVEDP) (p = 0.04) were significantly lower in the NC group than in the C group after aortic declamping. Cardiac output and myocardial contractility (dP/dtmax) were also enhanced in the group receiving NC, but the difference was not statistically significant. At 30 minutes after reperfusion, the coronary production (coronary sinus-aorta) of thiobarbituric acid reactive substances correlated inversely with cardiac output (r = -0.90, p = 0.001) and stroke volume (r = -0.82, p = 0.007). The effect of NC on lipid peroxidation seems to be modest and therefore the target of NC is unclear. NC would appear, however, to be a beneficial additive in the crystalloid cardioplegia in terms of functional recovery.
在主动脉交叉钳夹期间,心肌会遭受整体缺血,钳夹解除后会出现再灌注。再灌注期间游离氧自由基的生成增加,导致心律失常和心功能受损。本研究旨在评估新型抗氧化剂尼他卡朋(NC)对体内心脏再灌注损伤的影响。12头猪接受麻醉,开胸后将主动脉和右心房插管进行体外循环。对照组(n = 6)仅用4℃晶体心脏停搏液使心脏停搏,NC组(n = 6)在心脏停搏液中加入NC(50μM)。每20分钟添加一次心脏停搏液。主动脉交叉钳夹1小时后,采集用于氧化应激分析的血样,并持续监测血流动力学参数90分钟。主动脉钳夹解除后,NC组的心率(p = 0.04)和左心室舒张末期压力(LVEDP)(p = 0.04)显著低于C组。接受NC的组心输出量和心肌收缩力(dP/dtmax)也有所增强,但差异无统计学意义。再灌注30分钟时,硫代巴比妥酸反应性物质的冠状动脉生成(冠状窦 - 主动脉)与心输出量(r = -0.90,p = 0.001)和每搏输出量(r = -0.82,p = 0.007)呈负相关。NC对脂质过氧化的作用似乎较小,因此NC的作用靶点尚不清楚。然而,就功能恢复而言,NC似乎是晶体心脏停搏液中一种有益的添加剂。