Böning Andreas, Rohrbach Susanne, Kohlhepp Lukas, Heep Martina, Hagmüller Stefanie, Niemann Bernd, Mühlfeld Christian
Department of Cardiovascular Surgery, Justus-Liebig University Gießen, Germany.
Institute of Physiology, Justus-Liebig University Gießen, Germany.
Exp Gerontol. 2015 Jul;67:3-8. doi: 10.1016/j.exger.2015.04.012. Epub 2015 Apr 23.
Senescent patients exhibit an elevated perioperative risk for cardiac dysfunction, hemodynamic depression and subsequent cardiac death compared to young patients. Despite the fact that a growing proportion of cardiac surgery patients are octogenarians, cardioplegic regimes remain comparable across patients of all ages. We compared the hemodynamic performance, metabolic parameters and ultrastructural changes in adult and senescent rat hearts after application of Buckberg's blood cardioplegia (BCP) to evaluate differences between the age groups regarding postischemic myocardial function and cellular ultrastructure.
Hearts of adult (young adult group, 3-4 months) and senescent (old group, 24 months) male Wistar rats were excised and inserted into a blood perfused isolated heart apparatus (Langendorff perfusion). After a stabilization period of 30 min, in 16 adult and 16 senescent hearts, Buckberg BCP was administered antegradely and repeated every 20 min. Six young adult and 3 senescent hearts served as ischemia control. After an aortic clamping time of 90 min an antegrade hot shot was administered. During reperfusion ex vivo cardiac functional parameters were recorded, including coronary blood flow, left ventricular developed pressure (LVDP) and velocity of myocardial contraction or relaxation (+/-dp/dt). Oxygen consumption and lactate production of the hearts were calculated. After perfusion fixation, the hearts of five rats in each BCP group and 3 rats in each ischemia group were investigated for cellular edema and mitochondrial damage by morphometry using transmission electron microscopy.
While recovery of cardiac function after 90 min of unprotected ischemia was significantly impaired in senescent hearts, functional recovery after ischemia protected by BCP was similar in adult and senescent hearts. Mitochondrial ultrastructure was severely damaged in both age groups after 90 min ischemia, but well preserved in both BCP groups. The qualitative analysis was confirmed by the morphometric cellular edema index and the volume-to-surface ratio of the mitochondria. Myocardial oxygen consumption was highest and lactate production was lowest in senescent hearts.
Senescent rat hearts were more susceptible to unprotected ischemia/reperfusion injury than young adult hearts. When protected by BCP, we found no difference in hemodynamic performance between adult and senescent hearts indicating preserved myocardial protection even in senescent individuals.
与年轻患者相比,老年患者围手术期出现心脏功能障碍、血流动力学抑制及随后心源性死亡的风险升高。尽管心脏手术患者中八旬老人的比例日益增加,但所有年龄段患者的心脏停搏方案仍类似。我们比较了应用巴克伯格血液停搏液(BCP)后成年和老年大鼠心脏的血流动力学表现、代谢参数及超微结构变化,以评估不同年龄组在缺血后心肌功能和细胞超微结构方面的差异。
切除成年(青年成年组,3 - 4个月)和老年(老年组,24个月)雄性Wistar大鼠的心脏,将其插入血液灌注的离体心脏装置(Langendorff灌注)。在30分钟的稳定期后,对16只成年和16只老年心脏进行顺行性BCP给药,每20分钟重复一次。6只青年成年和3只老年心脏作为缺血对照。在主动脉夹闭90分钟后进行顺行性热灌注。在体外再灌注期间记录心脏功能参数,包括冠状动脉血流量、左心室舒张末压(LVDP)和心肌收缩或舒张速度(±dp/dt)。计算心脏的氧耗量和乳酸生成量。灌注固定后,使用透射电子显微镜通过形态计量学研究每个BCP组中5只大鼠的心脏以及每个缺血组中3只大鼠的心脏的细胞水肿和线粒体损伤情况。
在未保护的缺血90分钟后,老年心脏的心脏功能恢复明显受损,而BCP保护的缺血后成年和老年心脏的功能恢复相似。在缺血90分钟后,两个年龄组的线粒体超微结构均严重受损,但在两个BCP组中均保存良好。形态计量学细胞水肿指数和线粒体体积与表面积比证实了定性分析结果。老年心脏的心肌氧耗量最高,乳酸生成量最低。
老年大鼠心脏比青年成年心脏更容易受到未保护的缺血/再灌注损伤。当用BCP保护时,我们发现成年和老年心脏的血流动力学表现没有差异,这表明即使在老年个体中也能保持心肌保护作用。